Using Video Analysis and Machine Learning in ADHD Diagnosis

NEWS TUESDAY: Machine Learning and The Possible Future of Diagnosing ADHD

Objective and automatic assessment approach for diagnosing attention-deficit/hyperactivity disorder based on skeleton detection and classification analysis in outpatient videos

Typically, clinicians rely on both subjective and objective observations, patient interviews and questionnaires, as well as reports from family and (in the case of children) parents and teachers, in order to diagnose ADHD. 

A group of researchers are aiming to find a diagnostic test that is purely objective and utilizes recent technological advancements. The method they developed involves analyzing videos of children in outpatient settings, focusing on their movements. The study included 96 children, half of whom had ADHD and half who did not.

How It Works

  1. Video Recording: Children were recorded during their outpatient visits.
  2. Skeleton Detection: Using a tool called OpenPose, the researchers detected and tracked the children's skeletons (essentially a map of their body's movements) in the videos.
  3. Movement Analysis: The researchers analyzed these movements, looking at 11 different movement features. They specifically focused on the angles of different body parts and how much they moved.
  4. Machine Learning: Six different machine learning models were used to see which movement features could best distinguish between children with ADHD and those without.

Key Findings

  • Movement Differences: Children with ADHD showed significantly more movement in all the features analyzed compared to children without ADHD.
  • Thigh Angle: The angle of the thigh was the most telling feature. On average, children with ADHD had a thigh angle of about 157.89 degrees, while those without ADHD had an angle of 15.37 degrees.
  • High Accuracy: Using thigh angle alone, the model could diagnose ADHD with 91.03% accuracy. It was very sensitive (90.25%) and specific (91.86%), meaning it correctly identified most children with ADHD and correctly recognized most children without it.

This new method could potentially provide a more objective way to diagnose ADHD, reducing the reliance on subjective observations and reports. It can help doctors make more accurate diagnoses, ensuring that those who need help get it and that those who don't aren't misdiagnosed.

May 28, 2024

Exploring Gut Microbiota and Diet in Autism and ADHD: What Does the Research Say?

In recent years, there has been growing interest in understanding the connection between our gut microbiota (the community of microorganisms in our digestive system) and various neurodevelopmental disorders like autism spectrum disorder (ASD) and attention-deficit hyperactivity disorder (ADHD). A new study by Shunya Kurokawa and colleagues dives deeper into this area, comparing dietary diversity and gut microbial diversity among children with ASD, ADHD, their normally-developing siblings, and unrelated volunteer controls. Let's unpack what they found and what it means.

The Study Setup

The researchers recruited children aged 6-12 years diagnosed with ASD and/or ADHD, along with their non-ASD/ADHD siblings and the unrelated non-ASD/ADHD volunteers. The diagnoses were confirmed using standardized assessments like the Autism Diagnostic Observation Schedule-2 (ADOS-2). The study looked at gut microbial diversity using advanced DNA extraction and sequencing techniques, comparing alpha-diversity indices (which reflect the variety and evenness of microbial species within each gut sample) across different groups. They also assessed dietary diversity through standardized questionnaires.

Key Findings

The study included 98 subjects, comprising children with ASD, ADHD, both ASD and ADHD, their non-ASD/ADHD siblings, and the unrelated controls. Here's what they discovered:

Gut Microbial Diversity: The researchers found significant differences in alpha-diversity indices (like Chao 1 and Shannon index) among the groups. Notably, children with ASD had lower gut microbial diversity compared to unrelated neurotypical controls. This suggests disorder-specific differences in gut microbiota, particularly in children with ASD.

Dietary Diversity: Surprisingly, dietary diversity (assessed using the Shannon index) did not differ significantly among the groups. This finding implies that while gut microbial diversity showed disorder-specific patterns, diet diversity itself might not be the primary factor driving these differences.

What Does This Mean?

The study highlights intriguing connections between gut microbiota and neurodevelopmental disorders like ASD and ADHD. The lower gut microbial diversity observed in children with ASD points towards potential links between gut health and the pathophysiology of ASD. Understanding these connections is crucial for developing targeted therapeutic interventions.

Implications and Future Directions

This research underscores the importance of considering gut microbiota in the context of neurodevelopmental disorders. Moving forward, future studies should account for factors like co-occurrence of ASD and ADHD, as well as carefully control for dietary influences. This will help unravel the complex interplay between gut microbiota, diet, and neurodevelopmental disorders, paving the way for innovative treatments and interventions.

In summary, studies like this shed light on the intricate relationship between our gut health, diet, and brain function. By unraveling these connections, researchers are opening new avenues for understanding and potentially treating conditions like ASD and ADHD.

April 9, 2024

Meta-analysis reports weak evidence for mindfulness interventions for children and adolescents with ADHD

Meta-analysis Reports Weak Evidence for Mindfulness Interventions for Children and Adolescents with ADHD

Mindfulness involves focusing on the present moment. Mindfulness meditations include choosing a point of focus, such as breathing, and focusing on it continuously. They may also involve focusing single-mindedly on body movements, as in Yoga.

Mindfulness involves focusing on the present moment. Mindfulness meditations include choosing a point of focus, such as breathing, and focusing on it continuously. They may also involve focusing single-mindedly on body movements, as in Yoga. This could be potentially useful because in focusing on the present moment with attention and emotion regulation, it addresses regulatory capacities impaired in ADHD.

Previous studies of efficacy of mindfulness interventions have been inconclusive, limited by low methodological quality. A Taiwanese study team tried to remedy this with a fresh meta-analysis of randomized controlled trials (RCTs).

The team included three types of RCTs: yoga intervention, mindfulness-based psychological intervention, and mediation training. There was a lot of variation in the length of individual sessions and in the total number of hours of intervention.

Five studies used a waiting list control group. Two studies used treatment as usual or standard care as control groups. Only four studies followed best practices of using an active control group, such as a listening task, behavioral therapy, cooperative activities, or an emotional education program.

Twelve studies scored between 4 and 7 points from a possible total of 10 points, suggesting at best moderate methodological quality. More seriously, there was no indication of patient and therapist blinding.

With all these limitations, the one nominally positive result was for improvement in ADHD symptoms. A meta-analysis of seven RCTs with a combined 184 participants found a large reduction in ADHD symptoms post-treatment that did not persist at follow-up a couple months later. But between-study variation (heterogeneity) was extreme, with evidence of publication bias. The authors did not offer a revised estimate of efficacy based on the standard trim-and-fill adjustment.

Two additional meta-analyses, of seven RCTs with 200 participants, and seven RCTs with 215 participants, found no improvement in either externalizing or internalizing behaviors post-treatment. This time there was no sign of publication bias in either case. For externalizing behaviors, there was negligible heterogeneity, and moderate heterogeneity for internalizing behaviors.

A meta-analysis of four RCTs combining 122 participants found a moderate improvement in child mindfulness post-treatment, but it was not statistically significant.

February 13, 2024

Meta-analysis indicates physical activity interventions lead to major improvements in motor proficiency in children and adolescents with ADHD

Meta-analysis Indicates Physical Activity Lead to Major Improvements in Motor Proficiency in Children with ADHD

The three primary symptoms of ADHD are inattention, hyperactivity, and impulsivity, which can significantly limit personal, social, academic, or occupational functioning.

The three primary symptoms of ADHD are inattention, hyperactivity, and impulsivity, which can significantly limit personal, social, academic, or occupational functioning. 

In addition to these symptoms, between a third and a half of children and adolescents with ADHD have limited motor proficiency. They are less coordinated or skilled in performing motor tasks than their peers. This in turn reduces their participation in physical activities. They are more likely to become overweight or obese. They are also more likely to have difficulty socializing with peers.

Current ADHD medications are effective at treating the primary symptoms of ADHD, but have no known effect on impaired motor proficiency. 

Noting that “physical activity interventions are relatively easy to implement and have been shown to improve motor proficiency compared to other behavioral therapies,” a joint Chinese and American study team set out to explore effect sizes through a systematic review of the peer-reviewed medical literature.

They identified ten studies with a total of 413 participants suitable for meta-analysis. Overall, physical activity interventions led to very large effect size improvements in motor proficiency. There was no sign of publication bias, but considerable variation (heterogeneity) between studies.

To address this heterogeneity, the team next investigated how different types of physical activity intervention affected outcomes. Those that concentrated on body coordination, fine motor control (manual dexterity, using the small muscles in our hands and wrists), and object control (moving or receiving an object such as a ball with accuracy) were found to be responsible for the large effect size improvements in motor proficiency, this time with low heterogeneity.

By contrast, strength and agility training and locomotor training (such as walking, running, hopping, skipping) were associated with smaller effect size improvements that were no longer significant, and continued to vary significantly between studies.

Despite combining ten separate studies, sample sizes remained small, even more so when broken down by type of physical activity intervention. Strength and agility interventions were associated with a medium-to-large effect size improvement, but with only four studies combining 131 participants, may simply have been under-powered to achieve significance. Similarly, locomotor interventions were associated with small-to-medium effect size improvement, but with only three studies and a total of 117 participants, may again have been under-powered. 

While these preliminary findings look promising, they will need additional studies and greater numbers of total participants to be confirmed.

March 7, 2024

Combating Misinformation about ADHD on Social Media and the Internet

Combating Misinformation about ADHD on Social Media and The Internet

In our digital age, the internet serves as a powerful platform for accessing health information. Yet, with this great power comes great responsibility. Misinformation, particularly concerning ADHD (Attention-Deficit/Hyperactivity Disorder), is rife online, leading to confusion, the perpetuation of stigma, and potentially harmful consequences for those affected by the disorder and their loved ones.

In our digital age, the internet serves as a powerful platform for accessing health information. Yet, with this great power comes great responsibility. Misinformation, particularly concerning ADHD (Attention-Deficit/Hyperactivity Disorder), is rife online, leading to confusion, the perpetuation of stigma, and potentially harmful consequences for those affected by the disorder and their loved ones. This blog will delve into some of these misconceptions, their impacts, and how to ensure the ADHD information you come across online is reliable, with a special emphasis on a recent study examining ADHD content on TikTok.

The Misinformation Problem

ADHD is a neurodevelopmental disorder that affects both children and adults. It's characterized by patterns of inattention, impulsivity, and hyperactivity that are persistent. Despite its recognition as a well-documented medical condition, it is often misunderstood, partly due to widespread misinformation.

Common ADHD misconceptions include:

ADHD is not a real disorder: This belief is found scattered across online forums, and even some ill-informed news articles.

ADHD is a result of bad parenting: Numerous online discussions blame parents for their child's ADHD. However, research has shown that ADHD has biological origins and is not a result of parenting styles.

ADHD only affects children: Many websites and social media posts promote this myth, but ADHD can continue into adulthood.

ADHD medication leads to substance abuse: Certain posts on social media may wrongly claim that ADHD medication leads to substance abuse.

A recent study explored the quality of ADHD content on TikTok, a popular video-sharing social media platform. Researchers investigated the top 100 most popular ADHD-related videos on the platform. Shockingly, they found that 52% of these videos were classified as misleading, while only 21% were categorized as useful. The majority of these misleading videos were uploaded by non-healthcare providers.

The Impact of Misinformation

Misinformation about ADHD can have harmful impacts on individuals with the disorder and their families:

Delayed diagnosis and treatment: Misinformation can deter individuals and parents from seeking professional help, leading to delays in diagnosis and treatment.

Increased stigma: False information can amplify societal stigma about ADHD, leading to misunderstanding and discrimination.

Harmful treatment approaches: Misinformation can lead individuals to opt for ineffective or even harmful treatments.

The proliferation of misleading ADHD content on platforms like TikTok only amplifies these problems. The TikTok study found that while the videos were generally understandable, they had low actionability — meaning they offered little practical advice for managing ADHD.

Identifying Reliable Information

Given the prevalence of misinformation, it's crucial to be able to distinguish between reliable and unreliable information about ADHD. Here are some pointers:

Use reputable sources: Trustworthy information often comes from recognized health organizations, government health departments, or reputable medical institutions.  Some examples are NIH, Mayo Clinic, CDC and

Be wary of fake experts: If you see info from a self-proclaimed expert, you can check to see if they are really an expert by going to  Or go to to see if they’ve ever written anything about ADHD that has been approved by their peers.

Look for citations: Reliable sources often cite scientific research to back their claims.

Beware of sensational headlines: Clickbait headlines often oversimplify complex topics like ADHD.

Consult a professional: If you're unsure about any information, consult a healthcare professional.

The TikTok study's findings underscore the importance of these guidelines, as healthcare providers tended to upload higher quality and more useful videos compared to non-healthcare providers.

In our era of digital information, the challenge of separating ADHD facts from fiction is significant but not insurmountable. By becoming discerning consumers of online information, we can help prevent the spread of misinformation, support those affected by ADHD, and foster a more informed and understanding society. It's also essential for clinicians to be aware of the extent of health misinformation online and its potential impact on patient care. This way, they can guide their patients toward reliable sources and away from misleading content.

March 11, 2024

Two new meta-analyses evaluate digital interventions for treating ADHD

Two New Meta-analyses Evaluate Digital Interventions for Treating ADHD

There is increasing interest in digital interventions to treat ADHD symptoms and to overcome deficits in executive functioning that are associated with this disorder. Executive functions such as working memory and cognitive speed originate in the frontal lobes of the brain, and guide voluntary goal-directed behavior.

There is increasing interest in digital interventions to treat ADHD symptoms and to overcome deficits in executive functioning that are associated with this disorder. Executive functions such as working memory and cognitive speed originate in the frontal lobes of the brain, and guide voluntary goal-directed behavior. They affect reading speed and accuracy, reading comprehension, attention, and impulse control, among other behaviors important to the ability to function in social, educational, and professional environments.

A Swedish study team based at Umeå University recently conducted a systematic search of the medical literature to explore the efficacy of computerized cognitive training (CCT) to improve executive functioning in adults with ADHD.

They included published randomized controlled trials (RCTs) involving adults 18 to 65 years old with a primary diagnosis of ADHD. The controls were participants with either a passive (wait-list) or active (modified simple training) intervention.

Nine RCTs with a combined total of 285 participants met inclusion criteria. Lumping together all cognitive outcome types, meta-analysis reported a small effect size improvement that was just barely statistically significant (p = .048, with p < .05 as the boundary).

However, when separated out by individual outcome types – executive functioning, cognitive speed, general short-term memory, or ADHD symptom severity – the meta-analyses found no improvements that reached statistical significance. 

Moreover, all RCTs except one were judged as high risk of bias.

While it is possible that additional studies enlarging the pool of participants could lead to statistical significance, all effect sizes were small to begin with, which is not encouraging.

The team concluded, “Considering the small positive effect in this meta-analysis for overall cognitive outcomes, together with the lack of evidence for far transfer, practitioners and individuals with ADHD should weigh the costs (resources and time) against the benefits of training.”

A South Korean study team recently concluded the first RCT-only meta-analysis of game-based digital therapeutics (DTx).

Combining 14 RCTs with a total of 1,183 participants, they found a small effect size improvement in parent-rated attention symptoms for game-based DTx interventions over controls. Nine RCTs combining 424 participants likewise found a small effect size improvement in teacher-rated attention symptoms. Between-study variation (heterogeneity) was negligible, and there was no indication of publication bias.

Combining five RCTs with a total of 256 participants, they reported small effect size improvements in both parent and teacher-rated hyperactivity/impulsivity symptoms. But they found no improvement in hyperactivity symptoms alone, whether evaluated by parents or teachers. Heterogeneity was in all instances negligible, with no sign of publication bias. 

The team then compared game-based DTx interventions with pharmaceutical treatment. 

ADHD medications outperformed game-based DTx interventions for improvement of attention symptoms in both parent (four RCTs with a total of 128 participants) and teacher (three RCTs with 92 participants) ratings, with small-to-medium effect sizes. Medications likewise prevailed in improving hyperactivity/impulsivity symptoms, whether rated by parents or teachers, with small-to-medium effect sizes.

The team concluded, “This study is the first direct and indirect meta-analysis to compare the efficacy of game-based DTx between control and medication according to the assessor in an RCT. In conclusion, game-based DTx had a more significant effect than the control. Additionally, between medication treatment versus DTx, medication was more effective.”

March 15, 2024

Meta-analysis finds methylphenidate, atomoxetine, and guanfacine use is associated with increased occurrence of headaches, but amphetamine use is not

Meta-analysis Finds Certain ADHD Meds Associated with Headaches, But Others Are Not

An international study team has just reported findings from a series of meta-analyses exploring associations between ADHD medications and headaches in children and adolescents.

An international study team has just reported findings from a series of meta-analyses exploring associations between ADHD medications and headaches in children and adolescents. 

First, to compare headache occurrence in individuals with ADHD to those without ADHD, the team performed a very large meta-analysis of twelve studies with over 2.7 million children and adolescents. Those with ADHD had twice the rate of headaches. 

There was no indication of publication bias, but there was considerable variation (heterogeneity) among studies, with crude odds ratios spanning from 0.9 to 3.37. Nevertheless, ten of the twelve studies pointed to higher odds among children and adolescents with ADHD. The four studies that controlled for age, sex, race, and other socioeconomic status variables reaffirmed the finding of a doubling of headache risk, this time with acceptable heterogeneity.

Three studies with a combined 7,755 participants found no difference in tension headaches, but five studies with over a quarter million persons found more than a doubling of the rate of migraine in children and adolescents with ADHD.

Next, the team performed meta-analyses of 58 randomized controlled trials (RCTs) of specific ADHD medications that met eligibility criteria for their systematic review. Because only a single eligible RCT apiece looked at bupropion and clonidine, these ADHD medications could not be included in the meta-analyses.

A meta-analysis of ten RCTs with a total of 2,672 participants found absolutely no association between use of amphetamines (including lisdexamphetamine) and headaches. Variation (heterogeneity) between studies was minimal, and there was no sign of publication bias.

A smaller meta-analysis of six RCTs with a combined 818 participants found a 24% increase in headaches among modafinil users, but it was not statistically significant, perhaps because of the much smaller combined sample size.

A meta-analysis of 17 RCTs with a total of 3,371 participants found a 33% increase in headache occurrence among methylphenidate users over placebo. Between-study variation (heterogeneity) was negligible, and there was absolutely no sign of publication bias. 

Similarly, a meta-analysis of 22 RCTs with a combined 3,857 participants reported a 29% increase in headache occurrence among atomoxetine users over placebo. Again, heterogeneity between studies was negligible, with absolutely no indication of publication bias.

Finally, a meta-analysis of eight RCTs with 1,956 participants found a 43% increase in headache occurrence among guanfacine users over placebo. Once again, with negligible heterogeneity and no indication of publication bias.

March 18, 2024

Pair of large U.S. cohort studies find little to no evidence of association between child and adolescent ADHD and digital media screen time

Large Cohort Studies Find Little-to-No Evidence of Association Between ADHD and Digital Media Screen Time

These days, kids in America are using digital devices like smartphones, tablets, computers, and TVs more than ever. Some people worry that this might be linked to ADHD, a condition that makes it hard for kids to pay attention and control impulsive behaviors.

These days, kids in America are using digital devices like smartphones, tablets, computers, and TVs more than ever. Some people worry that this might be linked to ADHD, a condition that makes it hard for kids to pay attention and control impulsive behaviors.

Two new studies tried to find out if there's a connection between screen time and ADHD. They used data from a big survey about kids' health across the U.S. One study looked at nearly 46,000 kids aged six to 17 over two years, from 2019 to 2020. The other study analyzed data from over 101,000 kids aged zero to 17, from 2018 to 2020.

The studies figured out if a child had ADHD by asking their caregivers if a doctor or health care provider ever told them that the child had ADHD.

Findings from the First Study

The first study found that kids who used screens for two to three hours a day were 22% more likely to have ADHD. Kids who used screens for four or more hours a day were 74% more likely to have ADHD compared to kids who used screens for less than two hours a day.

However, when the researchers considered other factors like the child's age, sex, poverty status, parents' education, race, and other health problems, the link between screen time and ADHD disappeared. They did find a small link between screen time and anxiety and depression, but no link at all with ADHD.

Findings from the Second Study

The second study also considered factors that might affect the results, but they didn't look at whether the child had other behavior problems. They found that for kids five years old and under, using screens for up to three hours a day didn't make them more likely to have ADHD. But kids who used screens for four or more hours a day were twice as likely to have ADHD compared to kids who used screens for less than an hour a day.

For kids aged six to 17, those who used screens for two hours a day were 11% more likely to have ADHD. Kids who used screens for three hours a day were 16% more likely, and kids who used screens for four or more hours a day were 32% more likely to have ADHD compared to kids who used screens for less than an hour a day.

Important Points to Remember

There are two key things to keep in mind from these studies:

  1. The differences found were pretty small.
  2. The first study suggested that anxiety and depression might actually be the reason for the link between screen time and ADHD, not the screen time itself.


Overall, these studies didn't find strong evidence that using digital devices causes ADHD in kids and teenagers. While there might be some small connections, other factors like anxiety and depression could play a bigger role.  Also, this was not a controlled experiment.  It is an observational study that cannot rule out many factors. It is importaant to consider that having ADHD causes one to use digital devices more frequently.

Meta-analysis finds physical activity associated with improved inhibitory function

Understanding the Role of Disinhibition in ADHD and the Impact of Physical Activity

A key component of ADHD is inhibition dysfunction disorder. Inhibition function involves control of one’s attention, thought, emotions, and behavior. That enables individuals to overcome strong external temptations or internal tendencies, and become more focused.

ADHD often includes a problem called disinhibition. This means that the brain struggles to control attention, thoughts, emotions, and behavior, which can lead to negative outcomes. Normally, inhibition helps people stay focused and avoid distractions, but when it fails, it's called disinhibition.

Children with ADHD who have problems with inhibition may face issues like substance abuse, self-harm, and antisocial behavior. Improving their inhibition can help them better manage themselves, do well in school, and have better relationships.

A team of researchers from China and South Korea explored whether physical activity could improve inhibition in children with ADHD. They reviewed studies and excluded those without control groups, those with poor quality assessments, and those involving other interventions like cognitive training or supplements. Their final analysis included 11 studies with 713 participants.

Key Findings on Physical Activity

  1. Frequency and Duration: Physical activity had to be done at least twice a week to show significant improvement in inhibition. Sessions needed to last between 45 minutes to an hour for noticeable benefits, with sessions over an hour showing even greater improvements.
  2. Consistency: Regular, long-term physical activity was more effective than single sessions.
  3. Intensity: Moderate-to-vigorous activities were better than moderate activities alone.
  4. Type of Activity:some text
    • Open-skilled sports (like ping-pong or taekwondo) which involve reacting to changing environments, showed the most significant improvements.
    • Closed-skill sports (like running or swimming) showed smaller improvements.
    • Exergaming (exercise using video games) had moderate benefits.
  5. Specific Improvements:some text
    • Improvements in response inhibition (the ability to control impulsive responses) were small to medium.
    • Improvements in interference suppression (preventing distractions from affecting working memory) were large.


The research concluded that physical activity can significantly improve the inhibition in children with ADHD, especially with regular, moderate-to-vigorous, open-skilled exercise done at least twice a week for an hour or more. Future studies should continue to explore this with high-quality methods to confirm these findings.

June 4, 2024

Meta-analysis finds limited benefits from computerized cognitive training

Meta-analysis Finds Limited Benefits from Computerized Cognitive Training

Computerized cognitive training (CCT) uses computers to try to strengthen cognitive skills and processes, reduce ADHD symptoms, and improve executive functioning. Executive functions are cognitive processes and mental skills that help individuals plan, monitor, and successfully execute their goals.

Computerized cognitive training (CCT) uses computers to try to strengthen cognitive skills and processes, reduce ADHD symptoms, and improve executive functioning. Executive functions are cognitive processes and mental skills that help individuals plan, monitor, and successfully execute their goals.

CCT programs target one or more cognitive processes such as motor inhibition, interference inhibition, sustained attention, and working memory. They ramp up task difficulty as performance improves. The goal is to harness the brain’s inherent adaptability (neuroplasticity) to boost performance. 

A European study team that previously probed the efficacy of CCT through meta-analysis had been unable to provide a robust estimate of effect size due to an insufficient number of high-quality trials with probably blinded outcomes. Noting that “there have been a considerable number of new RCTs [randomized controlled trials] published, many with larger samples, well-controlled designs and blinded outcomes,” the team performed an updated systematic review and meta-analysis.

They included RCTs with participants of any age who either had a clinical diagnosis of ADHD or were above cut-off on validated ADHD rating scales. RCTs had to have been peer-reviewed and published in an academic journal, and to have reported a validated outcome measure of ADHD symptoms, neuropsychological processes, and/or academic outcomes.

Fourteen RCTs with a combined total of 631 participants had probably blinded outcomes. Meta-analysis of these studies yielded no significant effect on either overall ADHD symptoms or hyperactivity/impulsivity symptoms. There was a marginally significant reduction in inattention symptoms, but the effect size was small. Between-study variation (heterogeneity) was negligible and there was no sign of publication bias.

Regarding academic outcomes, meta-analyses revealed no gain in arithmetic ability or reading fluency. There was a small but not statistically significant improvement in reading comprehension. Heterogeneity was minimal, with no indication of publication bias.

With two related exceptions, meta-analyses of RCTs measuring executive functions likewise reported no significant improvements in attention, interference inhibition (initial stage in controlling impulsive behavior), motor inhibition (follow-up stage in controlling impulsive behavior), non-verbal reasoning, processing speed, and set shifting (the ability to unconsciously shift attention between one task and another).

The exceptions were for working memory tasks. Meta-analysis of 15 RCTs with a combined 753 participants reported a highly significant small-to-medium effect size improvement in verbal working memory. A separate meta-analysis of nine RCTs with a total of 441 participants similarly reported a highly significant improvement in visuospatial working memory, this time with medium effect size.

The team concluded, “There was no empirical support for the use of CCT as a stand-alone intervention for ADHD symptoms based on the largest and most comprehensive meta-analysis of RCTs conducted to date. Small effects, of likely limited clinical importance, on inattention symptoms were found – but these were limited to the setting in which the intervention was delivered. Robust evidence of small- to-moderate improvements in visual-spatial and verbal STM/WM tasks did not transfer to other domains of executive functions or academic outcomes.”

Updated meta-analysis supports efficacy of guanfacine in treating ADHD

Updated Meta-analysis Supports Efficacy of Guanfacine in Treating ADHD

Guanfacine is a non-stimulant medication for ADHD. It is an Alpha-2 agonist that targets and excites receptors in the prefrontal cortex of the brain, the region that governs executive functions such as judgment, decision making, planning, and response suppression. These functions tend to be suboptimal in ADHD.

Guanfacine is a non-stimulant medication for ADHD. It is an Alpha-2 agonist that targets and excites receptors in the prefrontal cortex of the brain, the region that governs executive functions such as judgment, decision making, planning, and response suppression. These functions tend to be sub-optimal in ADHD.

Most treatment guidelines recommend stimulants as the preferred treatment for ADHD, because they respond faster, and studies show they have higher efficacy in reducing symptoms. But for individuals for whom treatment with stimulants is subpar, guidelines recommend non-stimulants as second-line treatment.

Previous meta-analyses have focused on efficacy among children and adolescents with ADHD. This meta-analysis, by a Chinese study team, expanded its reach to not only update the former, but also include studies of adults.

The team’s systematic search of the medical literature for double-blind randomized controlled trials (RCTs) identified eleven that could be combined for meta-analysis. With only a single study of efficacy for adults, however, no meta-analysis could be performed specific to persons 18 and older.

Meta-analysis of all eleven studies with a combined total of 2,623 participants found guanfacine to be roughly 75% more effective than placebo for reducing ADHD symptoms. Variation between studies (heterogeneity) was low. There was no sign of publication bias.

Breaking that down by length of time on guanfacine found no evidence of a dose-response effect, however. In fact, participants with less than ten weeks of treatment (seven RCTs, 1,771 participants) outperformed those with longer periods of treatment (four RCTs, 852 participants) with a narrow overlap in the 95% confidence limits.

The outcomes were also sensitive to the ADHD symptom scale used. Meta-analysis of RCTs using the Clinical Global Impression of Improvement treatment response score (four studies, 850 participants) reported no significant improvement, while RCTs relying on ADHD-Rating-Scale-IV (six studies, 1,128 participants) reported a significant improvement, but without providing a standardized effect size.

Finally, a meta-analysis of ten RCTs with a combined total of 2,273 persons found a 23% increase in treatment-emergent adverse events for guanfacine relative to placebo. The three most common such events in the guanfacine group were somnolence (38.6%), headache (20.5%), and fatigue (15.2%).

April 29, 2024

Inequities in ADHD diagnosis in the United States

Inequities in ADHD diagnosis in the United States

A transcontinental study team (California, Texas, Florida) used a nationally representative sample – the 2018 National Survey of Children’s Health – to query 26,205 caregivers of youth aged 3 to 17 years old to explore inequities in ADHD diagnosis.

A transcontinental study team (California, Texas, Florida) used a nationally representative sample – the 2018 National Survey of Children’s Health – to query 26,205 caregivers of youth aged 3 to 17 years old to explore inequities in ADHD diagnosis.  

With increasing accessibility of the internet in the U.S., more than 80% of adults now search for health information online. Recognizing that search engine data could help clarify patterns of inequity, the team also consulted Google Trends.

The team noted at the outset that “[d]ocumenting the true prevalence of ADHD remains challenging in light of problems of overdiagnosis (e.g., following quick screening rather than full evaluation incorporating multi-informant and multi-method data given limited resources) and underdiagnosis (e.g., reflecting inequities in healthcare and education systems).” Underdiagnosis is known to be influenced by lack or inadequacy of health insurance, inadequate public health funding, stigma, sociocultural expectations in some ethnic groups, and structural racism, among other factors.

After controlling for poverty status, highest education in household, child’s sex, and child’s age, the team reported that Black youth were a quarter (22%) less likely to receive ADHD diagnoses than their white peers. Latino/Hispanic youth were a third (32%) less likely and Asian youth three-quarters (73%) less likely to receive ADHD diagnoses than their white peers.

The team also found that state-level online search interest in ADHD was positively associated with ADHD diagnoses, after controlling for race/ethnicity, poverty status, highest education in household, child’s sex, and child’s age. However, the odds ratio was low (1.01), “suggesting the need for additional evaluation.” Furthermore, “There was no interaction between individual-level racial/ethnic background and state-level information-seeking patterns. … the state-level online information-seeking variation did not affect the odds that youth of color would have a current ADHD diagnosis over and above other included characteristics.” 

That could be due in part to the gap in high-speed broadband access between Black and Hispanic in contrast to white populations, but that would not explain the even larger gaps in diagnosis for Asian youth, who tend to come from more prosperous backgrounds.

The team concluded, “Persistent racial/ethnic inequities warrant systematic changes in policy and clinical care that can attend to the needs of underserved communities. The digital divide adds complexity to persistent racial/ethnic and socioeconomic inequities in ADHD diagnosis …”

Cohort Study Finds Association Between Parkinson’s Disease and ADHD

Nationwide cohort study finds association between Parkinson’s disease and ADHD

Parkinson’s disease is a chronic, progressive neurological disease, characterized by the drastic reduction of dopamine transporters and the dopaminergic neurons upon which they are expressed.

Parkinson’s disease is a chronic, progressive neurological disease, characterized by the drastic reduction of dopamine transporters and the dopaminergic neurons upon which they are expressed. The resulting symptoms include bradykinesia (slowness of initiation of voluntary movements), tremors, rigidity, and postural instability.

Taiwan’s National Health Service covers about 99 percent of its 24 million inhabitants and maintains complete records in its National Health Insurance Research Database. The Longitudinal Health Insurance Database2000 (LHID 2000) is a nationally representative subset of the latter.

Using the LHID 2000, a Taiwanese research team identified 10,726 patients with Parkinson’s disease. It paired them with an identical number of randomly selected non-Parkinson’s controls, matched by age, gender, and index date (first date of diagnosis of Parkinson’s disease).

The team then looked retroactively through the database to determine which of the 21,452 individuals had previously been diagnosed with ADHD. Fourteen of the 10,726 Parkinson’s patients had been diagnosed with ADHD, versus five of the 10,726 in the control group.

Parkinson’s patients were thus 2.8 times as likely to have had a previous diagnosis of ADHD as the controls. When adjusted for age, gender, and Carlson Comorbidity Index scores, they were 3.6 times as likely to have had a previous ADHD diagnosis.

The authors cautioned that this association between prior ADHD diagnosis and subsequent Parkinson’s diagnosis is not causal.

Only one in 766 of Parkinson’s patients (a seventh of one percent) had previously been diagnosed with ADHD. So even if there were any causal relationship, it would be extremely weak.

November 9, 2023

Daytime Sleepiness, Cognitive Function, and Adult ADHD

What’s the relationship between daytime sleepiness and cognitive functioning in adults with ADHD?

Sleep disorders are one of the most commonly self-reported comorbidities of adults with ADHD, affecting 50 to 70 percent of them.

Sleep disorders are one of the most commonly self-reported comorbidities of adults with ADHD, affecting 50 to 70 percent of them. A team of British researchers set out to see whether this association could be further confirmed with objective sleep measures, using cognitive function tests and electroencephalography (EEG).

Measured as theta/beta ratio, EEG slowing is a widely used indicator in ADHD research. While it occurs normally in non-ADHD adults at the conclusion of a day, during the day it signals excessive sleepiness, whether from obstructive sleep apnea or neurodegenerative and neurodevelopmental disorders. Coffee reverses EEG slowing, as do ADHD stimulant medications.

Study participants were either on stable treatment with ADHD medication (stimulant or non-stimulant medication) or on no medication. Participants had to refrain from taking any stimulant medications for at least 48 hours prior to taking the tests. Persons with IQ below 80 or with recurrent depression or undergoing a depressive episode were excluded.

The team administered a cognitive function test, The Sustained Attention to Response Task (SART). Observers rated on-task sleepiness using videos from the cognitive testing sessions. They wired participants for EEG monitoring.

Observer-rated sleepiness was found to be moderately higher in the ADHD group than in controls. Although sleep quality was slightly lower in the sleepy group than in the ADHD group, and symptom severity slightly greater in the ADHD group than the sleepy group, neither difference was statistically significant, indicating extensive overlap.

Omission errors in the SART were strongly correlated with sleepiness level, and the strength of this correlation was independent of ADHD symptom severity. EEG slowing in all regions of the brain was more than 50 percent higher in the ADHD group than in the control group and was highest in the frontal cortex.

Treating the sleepy group as a third group, EEG slowing was highest for the ADHD group, followed closely by the sleepy group, and more distantly by the neurotypical group. The gaps between the ADHD and sleepy groups on the one hand, and the neurotypical group on the other, were both large and statistically significant, whereas the gap between the ADHD and sleepy groups was not. EEG slowing was both a significant predictor of ADHD and of ADHD symptom severity.

The authors concluded, “These findings indicate that the cognitive performance deficits routinely attributed to ADHD … are largely due to on-task sleepiness and not exclusively due to ADHD symptom severity. … we would like to propose a simple working hypothesis that daytime sleepiness plays a major role in cognitive functioning of adults with ADHD. … As adults with ADHD are more severely sleep deprived compared to neurotypical control subjects and are more vulnerable to sleep deprivation, in various neurocognitive tasks they should manifest larger sleepiness-related reductions in cognitive performance. … One clear testable prediction of the working hypothesis would be that carefully controlling for sleepiness, time of day, and/or individual circadian rhythms would result in a substantial reduction in the neurocognitive deficits in replications of classic ADHD studies.”

March 31, 2022

Meta-Analysis: Is Neurofeedback A Viable Treatment For ADHD?

New meta-analysis of 17 RCTs finds no evidence of efficacy for neurofeedback treatment of ADHD

Neurofeedback, also known as EEG (electroencephalogram)biofeedback, is a treatment that seeks to alleviate symptoms of various neurological and mental health disorders, including ADHD. It does this through immediate feedback from a computer program that tracks a client's brainwave activity, then uses sound or visual signals to retrain these brain signals. This in principle enables patients to learn to regulate and improve their brain function and reduce symptoms.

An Iranian study team recently performed a systematic search of the peer-reviewed medical literature. It identified seventeen randomized-controlled trials (RCTs) of neurofeedback treatment for children and adolescents with ADHD that could be aggregated for meta-analysis.

A meta-analysis of twelve RCTs with a combined total of 740 youths looked at parent ratings of changes in hyperactivity/impulsivity symptoms, and separately of changes in inattention symptoms. In both instances, the net pooled effect centered on zero.

A meta-analysis of nine RCTs with a combined total of 787 youths examined teacher ratings. Once again, the pooled change hyperactivity/impulsivity symptoms centered on zero. For inattention symptoms, the teacher ratings centered on a tiny improvement, but it did not approach statistical significance. The 95% confidence interval stretched well into negative territory.

There was no sign of publication bias. Between-study heterogeneity, on the other hand, was high, with some small sample size RCTs pointing to reduced symptoms, and other small sample size RCTs pointing to increased symptoms. However, the RCTs with the larger sample sizes clustered close around zero effect size.

The authors concluded,"The results provide preliminary evidence that neurofeedback treatment is not an efficacious clinical method for ADHD."

March 23, 2022

"Time-Blindness" Found to Be a Consistent Feature of ADHD

Meta-analysis finds consistent time perception impairments in persons with ADHD

An international study team conducted the first meta-analysis of studies examining differences in time perception between persons with ADHD and normally developing controls. A systematic search of the peer-reviewed medical literature identified 55 studies that could be combined into various subgroups for meta-analysis.

A meta-analysis of 25 studies with a combined 1,633 participants looking at time discrimination found a medium effect size deficit among persons with ADHD in the number of correct comparisons between the length of two signals. There was little between-study heterogeneity and no sign of publication bias.

Turning to time estimation, a meta-analysis of eight studies with a combined 1,024 participants found a small-to-medium effect size increase in absolute errors (i.e., the absolute value of deviation between the specified and the estimated time interval, representing the absolute amount of error regardless of its direction) among persons with ADHD, compared to controls. Again, there was little between-study heterogeneity and no sign of publication bias.

A meta-analysis of seven studies with combined 380 participants looked at differences in time production, in which they had to produce a previously specified time interval by pressing and holding a button. In this case, those with ADHD manifested a small effect size increase in absolute error relative to their normally developing counterparts. There was moderate between-study heterogeneity and no sign of publication bias.

Finally, a meta-analysis of 26 studies with combined 2,364 participants examined differences in time reproduction, in which they had to reproduce the duration of a previously presented stimulus by pressing and holding a button. Here, those with ADHD exhibited a medium effect size increase in absolute error. There was moderate between-study heterogeneity and no indication of publication bias.

An acknowledged limitation of these meta-analyses was the inability to assess the effects of pharmacological treatment. In addition, 84% of the studies did not report the ethnicity of participants.

The team concluded, "We found meta-analytic evidence of significant deficits in individuals with ADHD across all timing paradigms ... individuals with ADHD have difficulties to discriminate stimuli that vary from each other for only several milliseconds, and they are more variable in their time estimates of several seconds irrespective of the paradigm examined, which may both be driven by their lowered alertness levels."

They suggested that this might eventually become a criterion to help diagnose ADHD: "Our findings have possible clinical implications, albeit not currently directly applicable to the clinical practice. As timing has been proposed as an independent neuropsychological pathway to ADHD, timing tasks should be considered in the clinical assessment of ADHD to better characterize the clinical profile of the patient... To characterize further the phenotype of the patient during the diagnostic process that may deserve clinical attention, we suggest developing a tool based on the time estimation paradigm. The time estimation accuracy score not only represents an intuitive score reflecting faster internal clock mechanisms in individuals with ADHD, but the paradigm also shows high internal consistency and test-retest reliability, allowing for a reliable assessment of developmental or interventional changes in timing abilities related to developmental factors or external interventions."

March 21, 2022

Cognitive Treatment for ADHD Symtoms May Be Uneffective

Meta-analysis finds no significant effect of cognitive treatment on ADHD symptoms and executive functioning when randomized controlled trials are blinded

A Chinese study team performed a systematic search of peer-reviewed journal literature to identify randomized controlled trials (RCTs) examining the efficacy of cognitive training as a treatment for youths with ADHD.

Seventeen RCTs with a combined total of 1,075 participants met standards for inclusion in a series of meta-analyses. Seven RCTs used waitlist controls, seven used placebo training, two used treatment-as-usual, and one used active knowledge training. Participants were unmediated in four RCTs, with varying proportions of medicated participants in the remaining thirteen.

A meta-analysis of 15 RCTs, with a combined 789 participants, assessed changes in inattention symptoms following treatment, as rated by parents or clinicians. It found a small-to-medium effect size improvement in symptoms of inattention. There was no indication of publication bias, but between-study heterogeneity was very high.

But that gain vanished altogether when combining only the six RCTs that were blinded, meaning the symptom evaluators had no idea which participants had received cognitive treatment and which participants had not. There was zero difference between the treatment and control groups. Significantly, between-study heterogeneity also diminished markedly, becoming low to moderate.

A second meta-analysis, of 15 RCTs with a combined 723 participants, assessed changes in hyperactivity/impulsivity symptoms following treatment, as rated by parents or clinicians. It found no significant difference between participants who received cognitive training and controls. There was no sign of publication bias, and between-study heterogeneity was moderate-to-high.

The three remaining meta-analyses looked for improvements in executive functions, using the Behavior Rating Inventory of Executive Function (BRIEF).

A meta-analysis of 13 RCTs, with a combined 748 participants, found a small-to-medium effect size improvement in the global executive composite index of BRIEF, as evaluated by parents. There was no sign of publication bias, and between-study heterogeneity was moderate-to-high.

But that improvement again disappeared altogether when considering only the five RCTs that were blinded. Between-study heterogeneity also became insignificant.

A meta-analysis of 6 RCTs with 401 participants found no significant improvement in the behavioral regulation index of BRIEF. Heterogeneity was negligible.

Finally, a meta-analysis of 7 RCTs with 463 participants also found no significant improvement in the metacognition index of BRIEF. In this case, between-study heterogeneity was high.

While acknowledging that "when analyses were set in blinded measures, effect sizes were not statistically significant," the author nevertheless concluded, "In summary, multiple cognitive training alleviates the presentation of inattention and improves general executive function behaviors in children with ADHD." This suggests an underlying bias on the part of the study team in favor of treatment even when not supported by best (i.e., blinded) methodological practices.

March 17, 2022

Comedication in Adults With ADHD

Comedication with ADHD medication in adults in a nationwide population cohort study

Individuals who are prescribed ADHD medications are much more likely to also be prescribed other medications both for psychiatric and non-psychiatric disorders.

Persons with ADHD have known to have high rates of psychiatric comorbidities. There is also growing evidence of somatic (non-psychiatric) comorbid disorders among youths with ADHD, such as metabolic syndrome (which can lead to type 2 diabetes) and chronic inflammation (such as asthma and allergic rhinitis). Much less is known, however, about comorbid conditions in adults with ADHD.

An international team of researchers looked for indicators of comorbid conditions in a nationwide cohort study using Swedish national registers. The target population was Swedish residents between the ages of 18 and 64 in 2013 and more specifically those who had been prescribed ADHD medication. They identified over 41,000 individuals who met these criteria, including over twenty thousand young adults aged 18-29 years, over sixteen thousand middle-aged adults aged 30-49 years, and over four thousand older adults aged 50-64. The remainder of the overall cohort were used as controls.

Young adults receiving ADHD medications were four times as likely to also be receiving somatic medications, and older adults were seven times as likely. The highest rate of co-medication -roughly five times more frequent than among controls - was for respiratory system medications. The second most common was for alimentary tract and metabolic system medications, with odds over four times higher than for controls. Cardiovascular system medications were the next most common, with odds among young adults receiving ADHD medications over four times those of controls, though reducing with age to being twice as common in older adults with ADHD. Patterns were similar among men and women.

Adults receiving ADHD medications were far more likely to also be receiving other psychotropic medications. Middle-aged adults were 21 times as likely to be dispensed such medications as controls, older adults eighteen times more likely, and younger adults fifteen times more likely.

For young adults prescribed ADHD medications, the most prevalent co-prescriptions were for addictive disorders, which were dispensed at over 26 times the rate for controls. For middle-aged and older adults, on the other hand, the most prevalent co-prescriptions were for antipsychotics, which were likewise dispensed at over 26 times the rate for controls. Results remained consistent for individuals who had an ADHD diagnosis in addition to an ADHD prescription.

In addition, individuals receiving ADHD medications were also on average taking more types of prescriptions, rising from 2.5 classes of medications at age 18 to five classes at age 64. For controls, the equivalent numbers were 0.9 types of medications at age 18, rising to 2.7 at age 64.

Looking at specific somatic medications prescribed, those for respiratory conditions were ones typically prescribed for asthma and allergic reactions, reinforcing a previously known association. Insulin preparations also had high rates of co-prescription, again further confirming the known association with obesity and diabetes.

On the other hand, the most commonly dispensed alimentary tract and metabolic system medications included proton pump inhibitors, typically prescribed for gastric/duodenal ulcers and gastroesophageal reflux disease. Sodium fluoride, prescribed to prevent dental caries, was also prominent. Neither of these is an established association and warrants further exploration.

Turning to psychotropic medications, the most frequent prescriptions were with drugs used to treat addictive disorders and with antipsychotics. Rates of opioid co-prescription were also notably high, a source of concern given the higher proclivity of persons with ADHD to substance use disorders.

March 5, 2022

What We Know About ADHD in Female Populations

A new consensus statement updates what is known about ADHD in girls and women, and offers professional advice

Boys are three times as likely as girls to be diagnosed with ADHD, and anywhere from three to sixteen times more likely to be referred for treatment.

An international team of experts recently published a consensus statement addressing this discrepancy and offering guidance to rectify the imbalance and improve diagnosis and care for girls and women with ADHD. Here are some key conclusions.

ADHD symptoms:

-Experts caution that ADHD behaviors typically express themselves differently in boys than in girls.
-That in turn leads to gender-based biases in teachers and parents. In two studies in which teachers were shown vignettes of individuals with typical ADHD behaviors, switching from female to male names and pronouns led to higher rates of referral for support and treatment.


-A major reason for this different expression of ADHD in boys is that they have much higher rates of comorbid externalizing disorders, such as the conduct disorder and oppositional defiant disorder, leading them to break rules and get into fights in school. This no doubt contributes to lower rates of referral for girls.
-On the other hand, females are more likely to have comorbid internalizing disorders, such as emotional problems, anxiety, and depression. These may be interpreted as primary conditions, and the link to ADHD is missed altogether.
-Because ADHD has come to be associated with many externalizing disorders, it is then easy to fail to identify it when it is associated with internalizing disorders such as eating disorders.
-Untreated ADHD in girls can increase the risk of substance use disorders.

Associated vulnerabilities:

Children with ADHD are more likely to be unpopular with their peers and to experience rejection. Whereas boys are more likely to experience that rejection in physical ways, girls are more likely to experience it in social ways and through cyberbullying. That, in turn, contributes to lower self-esteem, which could explain some comorbid internalizing disorders.

Symptoms of hyperactivity/impulsivity, one of the two key components of ADHD, are associated with higher rates of risk-taking behavior:

- Like males with ADHD, females with ADHD have higher injury rates.
-Both males and females with ADHD are more likely to underachieve in school or drop out altogether.
-Overall, adolescents with ADHD become sexually active earlier, have more sexual partners, and are more frequently treated for sexually transmitted diseases than their normally developing peers. That also leads to higher rates of teenage and unplanned pregnancies.
-As with males with ADHD, females with ADHD have higher rates of criminal behavior than normally developing peers. While females with ADHD are still half as likely to be convicted of a crime than males with ADHD, one study showed they nevertheless are eighteen times more likely to be convicted of a crime than normally developing females.

Compensatory or coping behaviors:

- Girls may turn to drink alcohol, smoking cannabis, smoking cigarettes, or vaping nicotine to cope with emotional anguish, social isolation, and rejection.
-Some girls may seek to build social support through high-risk activities such as joining a gang, becoming promiscuous, and engaging in criminal behavior.

Triggers for possible referral

Ages 5-11:

-Bedwetting, nail-biting

Ages 5-16:

-Early sexualized behavior

Ages 5-18:

-Suspensions, expulsions, frequent detentions
-Poor attendance/truancy
-Consistent lateness, poor organization
-Academic difficulties, low academic self-esteem
-Conduct problems, conflicts with parents and peers
-Bullying (usually as victims)
-Regular tobacco and alcohol use
- Obesity and other eating disorders
- Repeated injuries
- Sleep difficulties
- Executive function difficulties
- Extreme emotional meltdowns

Ages 12 and above:

- Relationship problems, anxiety about relationships
- Social rejection, isolation
- Substance abuse, including alcohol
- Risky sexual behavior
- Underage or unwanted pregnancy
- Delinquency or criminal behavior (including shoplifting, vandalism)
- Low self-esteem
- Self-harm, suicidality

Ages 16 and above:

- Dropping out of school
- Losing jobs
- Parenting problems
- Criminality
- Financial difficulties
- Traffic crashes
- Internalizing conditions: depression, anxiety

Ages 18 and above:

- Gambling problems, compulsive shopping
- Personality disorder
- Chronic fatigue syndrome
- Fibromyalgia

The key message is not to disregard females because they do not present with the externalizing behavioral problems, or the disruptive, hard-to-manage boisterous, or loud behaviors typically associated with males with ADHD.


The authors emphasize that "comprehensive assessment should be completed to accurately capture the symptoms of ADHD across multiple settings, their persistence over time, and associated functional impairments. High rates of comorbidity are typically present. The assessment process is typically tripartite, involving the use of rating scales, a clinical interview, and ideally objective information from informants or school reports."

Rating scales: Ideally rely on those that provide female norms, making them more sensitive to female presentation.

Clinical interviews:

-Be mindful of age-appropriate, common-occurring conditions in females with ADHD, including autistic spectrum disorder, tics, mood disorders, anxiety, eating disorders, fibromyalgia, and chronic fatigue syndrome.
- Be alert to signs of self-harming behaviors(especially cutting), which peak in adolescence and early adulthood.
-Given that heritability of ADHD is high, ranging between 70-80% in both children and adults, be mindful that informants who are family members may also have ADHD (possibly undiagnosed) which may affect their judgment of "typical" behavior. The assessor should obtain specific examples of behavior from the informant and use these to make clinically informed judgments, rather than relying upon the informants' perception of what is typical or atypical.



- Recommendations for medication do not differ by sex, except that pharmacological treatment is generally not advised during pregnancy or breastfeeding.
- A systematic review and network meta-analysis recommended methylphenidate for children and adolescents and amphetamines for adults, taking into account both efficacy and safety. Larger confidence intervals about the tolerability and efficacy of bupropion, clonidine, and guanine were reported, indicating less conclusive results about the efficacy and tolerability of these oral medications. The use of medication should be followed up over time to verify if medications are effective and well-tolerated, and to manage the effects of related conditions(e.g. anxiety, depression) if they emerge.


- Cognitive behavioral therapy (CBT) together with psychoeducation (which can be provided to both patients and parent/guardians together or independently) are the best forms of psychological treatment.
- Parents and other guardians of teenage girls need to be shown how to identify deliberate self-harming or risky behavior.
- Adolescent girls may require assistance in addressing risky behavior (sexual risk, substance misuse) and improving self-management. Girls with ADHD are more vulnerable to sexual exploitation and have higher rates of early and unwanted pregnancy.
- Adults are more likely to require interventions to address employment problems, child-rearing, and parenting. Women with ADHD are also more vulnerable to sexual exploitation, including physical and sexual violence.
- Interventions should support attendance and engagement with education to avoid early school-leaving, diminished educational attainment, and associated vulnerabilities. While externalizing conditions have a greater impact on classroom behavior, internalizing conditions affect motivation and thus the ability to benefit from education.

Institutional outreach

- Educational, social care, occupational, and criminal justice system professionals should be trained to improve the detection and referral of ADHD in girls and women.
- Flexible learning systems and support with childcare can help women with ADHD return to education after having a baby.
- Depending on the country of residence, women who disclose their disability to their employer may be entitled to reasonable adjustments to the workplace to accommodate their condition.
- Low to no-cost apps are available to assist persons with ADHD with itineraries, lists, and reminders.
- Career planning should take into account that some occupations may provide a better fit for women with ADHD: "some individuals with ADHD show a preference for more stimulating environments, active, hands-on, or busy and fast-paced jobs."
- Persons with ADHD, both male and female, make up roughly a quarter of the prison population: "Evidence indicates that ADHD treatment is associated with reduced rates of criminality, is tolerated and effective in prison inmates, and improves their quality of life and cognitive function. This has led to speculation that effective identification and treatment of ADHD may help to reduce re-offending."

The authors concluded, "To facilitate identification, it is important to move away from the previously predominating disruptive boy stereotype of ADHD and understand the more subtle and internalized presentation that predominates in girls and women."

March 1, 2022

How Effective Is Exercise in Treating ADHD?

New meta-analysis explores effectiveness of physical exercise as treatment for ADHD

Noting that "Growing evidence shows that moderate physical activity (PA) can improve psychological health through enhancement of neurotransmitter systems," and "PA may play a physiological role similar to stimulant medications by increasing dopamine and norepinephrine neurotransmitters, thereby alleviating the symptoms of ADHD," a Chinese team of researchers performed a comprehensive search of the peer-reviewed journal literature for studies exploring the effects of physical activity on ADHD symptoms.

They found nine before-after studies with a total of 232 participants, and fourteen two-group control studies with a total of 303 participants, that met the criteria for meta-analysis.

The meta-analysis of before-after studies found moderate reductions in inattention and moderate-to-strong reductions in hyperactivity/impulsivity. It also reported moderate reductions in emotional problems and small-to-moderate reductions in behavioral problems.

The effect was even stronger among unmediated participants. There was a very strong reduction in inattention and a strong reduction in hyperactivity/impulsivity.

The meta-analysis of two-group control studies found strong reductions in inattention, but no effect on hyperactivity/impulsivity. It also found no significant effect on emotional and behavioral problems.

There was no sign of publication bias in any of the meta-analyses.

The authors concluded, "Our results suggest that PA intervention could improve ADHD-related symptoms, especially inattention symptoms. However, due to a lot of confounders, such as age, gender, ADHD subtypes, the lack of rigorous double-blinded randomized-control studies, and the inconsistency of the PA program, our results still need to be interpreted with caution."

February 21, 2022

Exploring how adult ADHD affects romantic relationships

Exploring how adult ADHD affects romantic relationships

ADHD symptoms are negatively associated with satisfaction in dating relationships but further study is needed to understand the mechanisms behind this, such as emotional regulation and deficits in inhibitory controls.

While romantic relationships can bring contentment and stability to adults with psychological disorders, conflict in such relationships adds incremental risk for developing depressive, anxiety, and substance use disorders. Moreover, persons with ADHD are more prone to such conflict than those without ADHD.

ADHD symptoms are negatively associated with satisfaction in dating relationships. One study found that female college students, blind to ADHD status, were less interested in male students with ADHD-Inattentive presentation than peers without ADHD. Another study found that college students who self-reported significant inattentive and hyperactive-impulsive symptoms also reported lower romantic relationship satisfaction than students not reporting such symptoms. A third study likewise found an inverse association between college student-reported inattentive symptoms and romantic relationship satisfaction, although it found no such association for self-reported hyperactive/impulsive symptoms.

This in turn has behavioral implications. One study found that college students with clinically elevated symptoms of inattention, hyperactivity/impulsivity, or both, reported higher levels of hostile conflict behavior with their partners than students without clinically elevated symptoms. Another study placed young couples through conflict resolutions. Couples in which one partner had ADHD demonstrated more negative and less positive conflict resolution behavior, and reported lower relational satisfaction, than couples in which neither partner had an ADHD diagnosis.

Worse yet, ADHD is a risk factor for dating violence. Two studies found that young adult males diagnosed with ADHD as children self-reported engaging in more frequent verbal and physical intimate partner violence than did their normally developing peers. Two more studies reported that men and women diagnosed with ADHD as children were at greater risk of becoming victims of such violence.

Adults with ADHD are also more likely to engage in risky sexual behavior. On average, they initiate sexual intercourse between one and two years earlier. They tend to have more partners and to make less frequent use of contraception than non-ADHD peers. As a result, adults with ADHD are also more likely to have unplanned pregnancies and to acquire sexually transmitted diseases.

Given these findings, it is hardly surprising that adults with ADHD report lower marital satisfaction than their normally developing peers. One study reported that 24 out of every 25 spouses of adults with ADHD felt their partner's symptoms interfered with their functioning in one or more domains, including general household organization/time management, child-rearing, and communication. Most studies have found that extramarital affairs, separation, and divorce are more frequent among couples in which one partner has ADHD.

ADHD is known to be highly heritable. That introduces further challenges. One study found that parents of children with ADHD are twice as likely to divorce by the time their child is eight years older than parents of children without ADHD. Another study found that disruptive child behavior is linked to parents arguing among themselves. This pattern was especially pronounced with parents who themselves had elevated ADHD symptoms. However, another study found that when both parents had ADHD symptoms, they were less likely to argue than when only one parent had such symptoms, or when neither did.

The authors note that there have been few longitudinal studies of the relationship to the behavior of adults with ADHD and that these are badly needed. This would help to understand how alcohol consumption relates to the development of relationship problems, for example.

Second, they point out that little is known about which subpopulations in the large population of adults with ADHD may be especially at risk for romantic relationship problems. Gender and history of maltreatment do not appear to be significant influences, but there is some evidence that alcohol and drug abuse may be a factor, as well as underachievement in adolescence. Moreover, the literature to date has focused on heterosexual Caucasian couples. There is a need for research with larger, more heterogeneous, population samples, and in particular with racial/ethnic minorities and LGBTQ+ adults.

Third, they suggest a need for further research on mediators between ADHD and romantic relationship problems. There are reasons to suspect a key role for emotion dysregulation and deficits in inhibitory controls. But studies to date have relied on self-reporting, which introduces respondent bias. Future studies should obtain ratings of ADHD and relationship functioning from other informants. There is also a need for studies focusing not just on younger adults, but also on older ones. Another critical need is for clinical trials testing the effectiveness of different interventions aiming to improve romantic relationship functioning.

The authors conclude, "Given that success in romantic relationships is considered by many to be a major developmental task and that ADHD persists for many affected individuals into adulthood, research on romantic adjustment of affected adults is surprisingly limited. The majority of existent published research points, however, to a robust association between ADHD and negative outcomes such as lower satisfaction in relationships, maladaptive conflict resolution styles, higher rates of relational dissolution, and behavioral issues such as unsafe sex and IPV."

February 19, 2022

Meta-Analysis Finds No Significant Benefit For ADHD Patients in tCDS

New meta-analysis finds no significant gains from transcranial direct stimulation (tCDS)

Based on current findings, repetitive transcranial magnetic stimulation cannot yet be officially recommended as an alternative neurotherapy for ADHD.

Noting that "despite a lack of solid evidence for their use, rTMS [repetitive transcranial magnetic stimulation]and tDCS [transcranial direct current stimulation] are already offered clinically and commercially in ADHD," and that a recent meta-analysis of ten tDCS studies found small but significant improvements in outcomes, but had several methodological shortcomings and did not include two studies reporting mostly null effects, a team of British neurologists performed a meta-analysis of all twelve sham-controlled, non-open-label, studies found in a comprehensive search of the peer-reviewed literature.

Ten of the twelve randomized-controlled trials used anodal stimulation of the dorsolateral prefrontal cortex, while the other two used anodal stimulation of the right inferior frontal cortex.

The trials explored several measures of cognition. The research team carried out a meta-analysis of all twelve trials, with a total of 232 participants, and found no significant improvement in attention scores from CDC, relative to sham stimulation. A second meta-analysis, of eleven trials with a total of 220 participants, assessed the efficacy of tDCS on improving inhibition scores, and again found no significant effect. A third meta-analysis, encompassing eight trials with a total of 124 participants, evaluated the efficacy of tDCS on improving processing speed scores, once again finding no significant effect.

The latter two meta-analyses approached the border of significance, prompting the authors to speculate that larger sample sizes could bring the results just over the threshold of significance. Even so, effect sizes would be small.

It is also possible that the trials focused on regions of the brain suboptimal for this objective, and thus the authors "cannot rule out the possibility that stimulation of other prefrontal regions (such as the right hemispheric inferior frontal cortex or dorsolateral prefrontal cortex or parietal regions), multiple session tDCS or tDCS in combination with cognitive training could improve clinically or cognitive functions in ADHD."

As to concerns about safety, on the other hand, "stimulation was well-tolerated overall."

The authors concluded that based on current evidence, tDCS of the dorsolateral prefrontal cortex cannot yet be recommended as an alternative Neurotherapy for ADHD.

February 15, 2022

Study Suggests Certain ADHD Meds May Have Protective Effect On The Brain

Might methylphenidate have a protective effect on brain development?

Methylphenidate, a psychostimulant, is among the drugs most frequently prescribed to children with ADHD.

Using magnetic resonance imaging(MRI), studies have shown that as children mature, those with ADHD differ from controls in developing regionally thinner cortices (the folded outer layer of the cerebrum that is essential to rational thought) and smaller lower basal ganglia(structures linked to the thalamus in the base of the brain and involved in the coordination of movement). The cortical differences were found in the right medial frontal motor region, the left middle/inferior frontal gyrus, and the right posterior parieto-occipital region in children with ADHD who were not taking psychostimulants.

A Dutch/Norwegian team of researchers conducted a randomized, double-blind, placebo-controlled trial with 96 males recruited from Dutch clinical programs. 48 were boys aged 10-12 years, and 47 were men between the ages of 23 and 40. None had previously been on methylphenidate. There were no significant differences in baseline age, ADHD symptom severity, estimated intelligence quotient, the proportion of right-handedness, or region of interest brain characteristics between the placebo and medication groups.

The trial was carried out during the standard 17-week waiting list time for evaluation and treatment to begin so that those receiving a placebo during the trial would not ultimately be at a disadvantage. The same MRI scanner was used for all measurements, both before and after treatment.

Among the boys, the methylphenidate group showed increased thickness in the right medial cortex, while the placebo group showed cortical thinning. In adults, both groups showed cortical thinning. When converted into an estimated mean rate of change in cortical thickness for the right medial cortex, boys taking methylphenidate could expect to lose about 0.01 mm per year, versus about 0.14 mm for boys not on methylphenidate.

In the right posterior cortex, scans also showed reduced thinning in the methylphenidate treatment group, though to a lesser extent. But there was no reduced thinning in the left frontal cortex.

The authors noted several limitations. The sample size was small. Second, "because we did not detect significant relationships between changes in cortical [regions of interest] and changes in symptom severity, the functional significance remains uncertain." Third, the follow-up period was relatively short, not allowing any assessment of the longer-term effects of the medication. Fourth, the differences in effects on the three brain regions examined were uneven, contrary to what had been expected from previous studies. They recommended replication with larger groups and longer follow-ups.

February 11, 2022

An Analysis Of ADHD Meds For ADHD Patients Also Receiving Opioid Treatment

Norwegian nationwide cohort study probes use of ADHD medication by ADHD patients undergoing treatment for opioid addiction

Despite roughly 1 in 5 patients in opioid recovery having ADHD, less than 1 in 20 of those patients will be treated with ADHD medication.

A key aspect of ADHD is greater difficulty controlling urges, so it is no surprise that there is a strong association between ADHD and substance use disorders, and opioid addiction in particular. It's also known that stimulants are effective in reducing ADHD symptoms. That would suggest that ADHD patients being treated for opioid addiction should also be treated for ADHD.

How extensive is such complementary treatment? A Norwegian research team used national register data from the Norwegian Prescription Database to find out. They began by identifying all 9,235 individuals who were dispensed at least one opioid agonist prescription from 2015 through 2017.

Opioid agonists, such as methadone and buprenorphine (Suboxone), while opioids have properties that prevent withdrawal and reduce cravings. They can do this precisely by substituting a less dangerous slow-acting opioid for a more dangerous rapid-acting one. They are also less addictive because they do not generate the intense highs of fast-acting opioids. That greatly reduces the risk of overdose, and risk of relapse to more hazardous opioid use, and promotes connections with the professional healthcare sector.

About 7,500 Norwegians are undergoing opioid agonist therapy at any given time. During the three-year study period, roughly three out of four were dispensed buprenorphine and the remainder methadone.

Although somewhere around one in five patients on opioid agonist therapy have ADHD (estimates range from11 to 33%), the team found that less than one in twenty were also dispensed ADHD medication. In 2015, only 3.5 percent received ADHD medication, rising slightly to 4.6 percent in 2017. In 2017, 62 percent received methylphenidate, 42 percent received various amphetamines, and only five percent received non-stimulant atomoxetine (there was some overlap).

Patients on buprenorphine were 60 percent more likely to be dispensed ADHD medications than those on methadone.

The authors concluded, "Co-prescribing of CAS [centrally acting stimulant] and atomoxetine was low in the OAT [opioid agonist therapy] population in Norway, relative to the expected prevalence of ADHD in this patient group. Considering that up to a third of the OAT population is estimated to have ADHD, only 3.5 to 4.6% of patients received both ADHD medication and OAT opioids in Norway in the period from 2015 to 2017. Randomized-controlled trials evaluating ADHD medication in different doses are needed to improve the treatment of ADHD in the OAT population."

February 9, 2022

Childhood Enterovirus Infection May Be a Risk Factor for ADHD

Taiwanese population study finds childhood enterovirus infection is associated with higher risk of ADHD

Population study finds that early enterovirus infection can put those individuals at a 25% higher risk for later ADHD diagnosis.

Enteroviruses (EV) are a class of RNA viruses. This group of viruses includes some no-longer endemic forms such as polio and some serious but rare forms that cause encephalitis and meningitis. The most common virus in this population and period (1999-2003) was EV71, which can have complications, sometimes fatal, especially for children under five years old. It has also been linked to various chronic diseases, many of them neurological.

Is it associated with the subsequent diagnosis of ADHD and, if so, to what extent?

Taiwan offers an excellent opportunity to study this in an entire population. This is because of its single-payer health care system. Its database "the National Health Insurance research database" covers 99.5 percent of the population.

The Taiwanese study team used a sub-database, the Longitudinal Health Insurance Database 2000, containing claims data from a million persons randomly sampled from the parent database.
From this database, the researchers identified over 49,000 EV patients. They excluded all who were 18 and older, were missing essential data or had been diagnosed with ADHD, epilepsy, topic diseases, coronary artery disease, stroke, rheumatoid arthritis, or systemic lupus erythematosus before being diagnosed with enterovirus. That left an EV cohort of 14,168,  who were matched with an equal number of non-EV individuals matched by age and sex.

After adjusting for age, sex, paternal occupation, and urbanization level of the residence, the EV cohort group was found to have a 25 percent greater risk for ADHD than the control group.

February 7, 2022

Exercise Found To Improve Certain ADHD Symptoms

Meta-analysis Finds Physical Activity Improves Executive Functions in Persons with ADHD

ADHD patients may substantially improve executive functions through persistent and protracted physical exercise.

Executive function(EF) is associated with the prefrontal cortex. It includes three core components: inhibitory control, cognitive flexibility, and working memory. Inhibitory control is the ability to avoid distractions, inhibit or control impulsive responses, and change to more thoughtful responses. Cognitive flexibility involves switching mental tasks or strategies, seeing problems from multiple perspectives, and identifying different ways of solving them. Working memory involves holding information in the mind ready for an ongoing processing.

Persons with neurodevelopmental disorders, including ADHD, are known to have EF deficits relative to their normally-developing counterparts.

An international research team conducted a comprehensive search of the peer-reviewed medical literature to identify studies that have explored how physical activity affects those deficits in persons with neurodevelopmental disorders, specifically ADHD.

They identified 34 studies with 1,058 participants, of which 13 with 400 looked specifically at ADHD. There was substantial geographic diversity in the ADHD studies, spanning the globe: the United States, Canada, Switzerland, Taiwan, South Korea, Iran, Israel, and Tunisia.

Among the ADHD studies, a meta-analysis found physical activity improved executive functions overall, with a large effect size. More specifically, it included twelve tests of inhibitory control, four for working memory, three for cognitive flexibility, and one each for switching and planning (there was often more than one tester in the study).

There was no sign of publication bias. There was, however, substantial heterogeneity between studies. A further breakdown indicated substantial divergence by type of physical activity, with a large effect size for sports, medium effect sizes for aerobic exercise and motor skills training, and small effect size for exergaming (video games that are also a form of exercise).

Session time also made a big difference. Sessions at least an hour long had large effect sizes, those between 45 minutes and an hour had medium effect sizes, and shorter sessions had smaller effect sizes.
Improvements in inhibitory control had large effect sizes, those in cognitive flexibility had medium-to-large effect sizes, and those in working memory had small-to-medium effect sizes. All of which suggest ADHD patients can substantially improve executive functions through persistent and protracted physical exercise.

February 5, 2022

Transcranial Direct Current Stimulation and Improving Response Inhibition

How effective is transcranial direct current stimulation at improving response inhibition?

Though initially offering some measurable results, further high-quality studies are needed to determine how effective tDCS may be in treating certain ADHD symptoms.

Inhibitory control is an essential cognitive control function whereby the prefrontal cortex blocks planned motor actions or interrupts motor actions already initiated by other parts of the brain. For example, someone might instinctually reach for a candy bar but then put it back upon thinking that eating it would conflict with a higher-level goal of cutting down on sugar consumption. Impairment of inhibitory control is a known characteristic of several psychiatric disorders, including ADHD.

Any generally safe treatment with the ability to at least partially reverse such impairment would therefore be useful. Researchers are currently experimenting with transcranial direct current stimulation, a non-invasive brain stimulation technique that uses a weak electrical current to stimulate specific regions of the brain.

What, then, do we know so far about its potential effectiveness for improving inhibitory control?

A team of experts at the University of Tübingen in Germany conducted a comprehensive search of the peer-reviewed medical literature to find out. They then performed a meta-analysis of 45 studies with a combined total of over 1,600 participants. All but four of the studies used sham or other active controls.

The overall meta-analysis found a significant but small improvement in response inhibition. But it also found evidence of publication bias. Adjusting for publication bias reduced the effect size in half, to a tiny but still significant improvement.

The meta-analysis relied on two behavioral tasks that require inhibitory control to measure response inhibition: the go-/no-task, and the stop-signal task. Separating these, there was no significant improvement in the go/no-go task performance. All the improvement was concentrated on the stop-signal task.

The authors noted, "A potential limitation of this meta-analysis is that we could not exhaustively model-dependent relationships between moderator variables (e.g., tDCS polarity and electrode placement)," and "Further high-quality studies are needed to investigate potential interactions between technical and functional parameters in tDCS research."

January 14, 2022

Transcranial Direct Current Stimulation: Can It Treat ADHD?

How effective and safe is transcranial direct current stimulation for treating ADHD?

ADHD is hypothesized to arise from 1) poor inhibitory control resulting from impaired executive functions which are associated with reduced activation in the dorsolateral prefrontal cortex and increased activation of some subcortical regions; and 2)hyperarousal to environmental stimuli, hampering the ability of the executive functioning system, particularly the medial frontal cortex, orbital and ventromedial prefrontal areas, and subcortical regions such as the caudate nucleus, amygdala, nucleus accumbens, and thalamus, to control the respective stimuli.

These brain anomalies, rendered visible through magnetic resonance imaging, have led researchers to try new means of treatment to directly address the deficits. Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique that uses a weak electrical current to stimulate specific regions of the brain.


A team of researchers from Europe and ran performed a systematic search of the literature and identified fourteen studies exploring the safety and efficacy of tDCS. Three of these studies examined the effects on ADHD symptoms. They found a large effect size for the inattention subscale and a medium effect size for the hyperactivity/impulsivity. Yet, as the authors cautioned, "a definite conclusion concerning the clinical efficacy of tDCS based on the results of these three studies is not possible."

The remaining studies investigated the effects on specific neuropsychological and cognitive deficits in ADHD:

  •  Working memory was improved by anodal stimulation - but not cathodal stimulation - of the left dorsolateral prefrontal cortex. Anodal stimulation of the right inferior frontal gyrus had no effect.
  •  Response inhibition: Anodal stimulation of the left or right dorsolateral prefrontal cortex was more effective than anodal stimulation of the bilateral prefrontal cortex.
  • Motivational and emotional processing was improved only with stimulation of both the dorsolateral prefrontal cortex and orbitofrontal cortex.

The fact that heterogeneity in the methodology of these studies made meta-analysis impossible means these results, while promising, cannot be seen as in any way definitive.


Ten studies examined childhood ADHD. Three found no adverse effects either during or after tDCS. One study reported a feeling of "shock" in a few patients during tDCS. Several more reported skin tingling and itching during tDCS. Several also reported mild headaches.

The four studies of adults with ADHD reported no major adverse events. One study reported a single incident of acute mood change, sadness, diminished motivation, and tension five hours after stimulation. Another reported mild instances of skin tingling and burning sensations.

To address side effects such as tingling and itching, the authors suggested reducing the intensity of the electrical current and increasing the duration. They also suggested placing electrodes at least 6 cm apart to reduce current shunting through the ski. For children, they recommended the use of smaller electrodes for better focus in smaller brains.

The authors concluded, "The findings of this systematic review suggest at least a partial improvement of symptoms and cognitive deficits in ADHD by tDCS. They further suggest that stimulation parameters such as polarity and site are relevant to the efficacy of tDCS in ADHD. Compared to cathodal stimulation, Anodal tDCS seems to have a superior effect on both the clinical symptoms and cognitive deficits. However, the routine clinical application of this method as an efficient therapeutic intervention cannot yet be recommended based on these studies ..."

January 10, 2022

Is There Any Hard Evidence in Support of Homeopathic Remedies for ADHD?

Is there any hard evidence in support of homeopathic remedies for ADHD?

According to Vox, "Homeopathy is a $1.2 billion industry in the US alone, used by an estimated 5 million adults and 1 million kids. It's become such a staple of America's wellness industry that leading brands such as Boiron and Hyland's are readily available at high-end health-focused chains like Whole Foods and sprouts, supermarkets like Ralph's, and superstores such as Walmart."

Yet, this highly profitable "wellness" industry has shown little to no interest in supporting randomized clinical trials (RCTs) to test the efficacy and safety of its products.

In a team of Italian physicians, Rana comprehensive search of the medical literature and found only nine RCTs exploring the efficacy and safety of homeopathic remedies for psychiatric disorders that met the selection criteria.

Only two of these RCTs addressed efficacy for ADHD, with a combined 99 participants. Neither reported any significant effect.

Combining them into a small meta-analysis likewise found no significant effect.

But that's not all. According to the study authors, "The paucity of published trials does not allow a reliable estimate of publication bias, which would require a larger number of studies. This is a major issue since it has been reported that, among completed trials of homeopathy registered on, only 46% were published within 2 years of completion, and among these, 25% altered or changed their primary outcomes. It is, therefore, possible that the results of the present meta-analysis are distorted because of selective publication."

The authors conclude, "The most surprising result of this meta-analysis is the paucity of available data from RCTs," and "Based on the very few available trials, homeopathy did not produce any relevant effect on symptoms of ADHD ... Ethical considerations should therefore prevent clinicians from recommending HRs [homeopathic remedies], which have a cost either for patients or for health care systems, until when a sufficient amount of solid evidence becomes available."

January 8, 2022

How Effective is Cognitive Training for Preschool Children?

How effective is cognitive training for preschool children?

Further study is needed, but meta-analysis shows small, but not insignificant, effects of pre-school interventions on core executive functions.

A German team of researchers performed a comprehensive search of the medical literature and identified 35randomized controlled trials (RCTs) published in English that explored this question. Participating children were between three and six years old. Children with intellectual disabilities, sensory disabilities, or specific neurological disorders such as epilepsy were excluded.

The total number of participating preschoolers was over three thousand, drawn almost exclusively from the general population, meaning these studies were not specifically evaluating effects on children with ADHD. But given that ADHD results in poorer executive functioning, evidence of the effectiveness of cognitive training would suggest it could help partially reverse such deficits.

RCTs assign participants randomly to a treatment group and a group not receiving treatment but often receiving a placebo. But RCTs themselves vary in risk of bias, depending on:

  • whether the control condition was passive (i.e. waiting list or no treatment) or active/sham (an activity of similar duration and intensity to the treatment condition)
  • whether the outcome was measured by subjective rating (e.g. by questionnaires, susceptible to reporting biases) or more objective neuropsychological testing;
  • whether the assessment of outcome was by blinded assessors unaware of participants' treatment conditions;
  • whether there was a risk of bias from participants dropping out of the trial.

After evaluating the RCTs by these criteria, the team performed a series of meta-analyses.

Combining the 23 RCTs with over 2,000 children that measured working memory, they found that cognitive training led to robust moderate improvements. Looking only at the eleven most rigorously controlled studies strengthened the effect, with moderate-to-large gains.

Twenty-six RCTs with over 2,200 children assessed inhibitory control. When pooled, they indicated a small-to-moderate improvement from cognitive training. Including only the seven most rigorously controlled studies again strengthened the effect, boosting it into the moderate effect zone.

Twelve RCTs with over 1,500 participants tested the effects of cognitive training on flexibility. When combined, they pointed to moderate gains. Looking at only the four well-controlled studies boosted the effect to strong gains. Yet here there was evidence of publication bias, so no firm conclusion can be drawn.

Only four studies with a combined total of 119 preschoolers tested the effects on ADHD ratings. The meta-analysis found a small but non-significant improvement, very likely due to insufficient sampling. As the authors noted, "some findings of the meta-analysis are limited by the insufficient number of eligible studies. Specifically, more studies are needed which use blinded assessments of subjective ratings of ADHD ... symptoms ..."

The authors concluded that their meta-analyses revealed significant, mostly medium-sized effects of the preschool interventions on core EFs [executive functions] in studies showing the low risk of bias."

January 2, 2022

Are There Short-term Effects of Air Pollution on Severity of ADHD symptoms?

Is there a short-term relationship between air pollution and severity of ADHD symptoms?

A South Korean research group studies associations between ADHD-related healthcare visits and short-term exposure to specific air pollutants.

Certain air pollutants can produce free radicals and inflammatory cytokines that can penetrate the central nervous system and affect behavior. Long-term exposure to air pollution has been associated with a higher risk of developing ADHD.

There has, however, been little focus on the short-term effects of exposure. Might there be any correlation between levels of air contaminants and subsequent healthcare visits of adolescents for severe spikes in ADHD symptoms (frequently but not always associated with comorbid conduct disorder, oppositional defiance disorder, or mood disorder), such as extreme hyperactivity, serious rule violations, theft, or aggression to people or animals?

A South Korean (Republic of Korea) research team explored this question through a nationwide cohort study using the database of the National Health Insurance Service, a single-payer system, that covers the entire population.

Using a time-series approach, they compared measured levels of three airborne pollutants - particulate matter with a diameter ≤ 10 μm (PM10), nitrogen oxide (NO2), produced by vehicular traffic, and sulfur dioxide (SO2), produced by manufacturing industries- with healthcare visits with a principal diagnosis of ADHD. They chose these three contaminants because they have been associated with ADHD in long-term studies. What made this approach feasible is that healthcare visits are typically unscheduled in Korea, making it possible to get quick medical attention.

The team divided the country into sixteen regions, looked at boys and girls separately, and also split adolescents into two age groups (10 to 14 years and 15 to 19 years). They estimated region-specific daily concentrations of the three pollutants from 318 government-run monitoring sites, located according to population density and distribution.

The researchers next calculated zero(same day) to five-day lag figures for ADHD-related healthcare visits in each region and ran meta-analyses on the time-series data.

There were 7,200 ADHD-related healthcare visits in the 2013-2015 study period. Major increases in PM10 levels were associated with increased ADHD-related healthcare visits from the day of the spike to three days later, peaking the day after the upturn. Major increases in SO2 levels were associated with increased ADHD-related healthcare visits from one to four days later, peaking the day following the upturn. Major increases in NO2 levels were associated with increased ADHD-related healthcare visits from one to four days later, peaking three days after the spike.

There were no significant differences between male and female adolescents, and between younger and older adolescents.

The strongest increased risk for ADHD-related healthcare visits was for NO2 spikes (up 47 percent), followed by SO2 spikes (up 27 percent), with PM10 spikes coming in last (up 12 percent).

Among the limitations, the authors were unable to evaluate the most hazardous types of particulate emissions, because the smaller-diameter PM2.5 particles (≤2.5 μm) have only been measured partially in South Korea since 2015. On the other hand, they pointed out that this was the first study to investigate associations between short-term air pollution exposure and ADHD-related healthcare visits, and that it included all ADHD-related healthcare visits in South Korea, making the possibility of selection bias negligible. They recommended conducting similar studies on other national populations.

December 31, 2021

ADHD Medication Least Likely to be Associated With Headache

Which ADHD medications are least likely to be associated with headaches?

A large-scale international research team conducts a systemic review of literature on ADHD medication and headaches.

There is strong evidence of the effectiveness of a variety of ADHD medicines in reducing ADHD symptoms. While some are more effective than others, another factor in deciding on a course of treatment is minimizing noxious side effects.

One of those side effects is a headache.

An international team of researchers from Sweden, Germany, the Netherlands, the United Kingdom, the United States, and Australia conducted a systematic review of the peer-reviewed medical literature about ADHD and headaches on the one hand, and ADHD medications and headaches on the other.

As a baseline, they performed a meta-analysis of twelve studies with a combined total of over 2.7 million participants that compared headache rates between youths with and without ADHD. Those with ADHD were twice as likely to suffer from headaches. This held even after limiting the meta-analysis to the four studies that adjusted for confounders.

Breaking down the results by type of headache revealed a fascinating distinction. There was no significant difference in rates of tension headaches, but migraines were 2.2 times as frequent among youths with ADHD.

This strong association between ADHD and migraines suggests looking for medications that are both effective and unlikely to further contribute to the odds of migraine.

Accordingly, the team examined associations between specific ADHD medications and headaches.

Stimulant medications are generally considered the most effective medications for treating ADHD. A meta-analysis of ten studies with 2,672 participants found no association between amphetamines and headaches. On the other hand, a meta-analysis of 17 studies with 3,371 participants found that methylphenidate increased the odds of headache by one-third (33%).

The non-stimulant atomoxetine is usually considered a second-tier treatment for those among whom stimulants are contraindicated. A meta-analysis of 22 studies encompassing 3,857 participants found it increased the odds of headache by 29%.

Guanfacine fared worst of the bunch. A meta-analysis of eight studies combining 1,956 participants found it increased the odds of headache by 43%.

Finally, a meta-analysis of six studies with a combined total of 818 participants found no association with headaches.

There was no indication of publication bias in any of the meta-analyses.

December 29, 2021

Youth ADHD is associated with elevated risks of subsequent psychotic disorder

Youth ADHD is associated with elevated risks of subsequent psychotic disorder

A French team of physicians conducted a systematic search of peer-reviewed literature to conduct a meta-analysis to examine the relationship between childhood ADHD and subsequent psychotic disorders.

What relationship, if any, might there be between childhood ADHD and subsequent psychotic disorders? Previous epidemiological studies have produced conflicting results.

A French team of physicians conducted a systematic search of the peer-reviewed literature to conduct a meta-analysis to examine this question in greater depth.
They pooled twelve studies with a combined total of 1.85 million participants, consisting of 124,095 with ADHD and just over 1.72 million controls.

The psychotic disorders analyzed included schizophrenia, schizophreniform disorder, schizotypal personality disorder, schizoaffective disorder, delusional disorder, brief psychotic disorder, and psychotic disorder not otherwise specified. These disorders had to be diagnosed after the diagnosis of ADHD in children and adolescents under 18 years old.

The meta-analysis found that persons diagnosed in childhood or adolescence with ADHD were well over four times more likely to have subsequent diagnoses of psychotic disorders than those without a diagnosis of ADHD. Limiting the meta-analysis to the six studies that were adjusted for confounders produced an identical result.

There were no statistically significant between-group differences for subgroup analyses comparing psychotic disorder or schizophrenia outcomes, cohort or case-control study design, and adjusted or unadjusted estimates. There were no significant differences between males and females.

Heterogeneity among studies was moderate (43%), and there was no sign of publication bias. Removing one study reduced heterogeneity to low levels (18%), while very slightly raising the odds of subsequent diagnosis of psychotic disorder. Looking only at the more restrictive diagnosis of schizophrenia also made no difference in the odds.

No matter how the data were analyzed, in all instances, the odds of subsequent diagnosis of psychotic disorder rose well over fourfold for those diagnosed with ADHD in their youth.

The authors concluded, "To improve our knowledge, further cohort studies should be conducted. Ideally, these studies would ensure a sufficiently long follow-up to account for the mean age at which P [psychotic disorders] develop. Such studies should consider the use of psychostimulants and the role of SUD [substance use disorder] in the causal path between ADHD and PD."

December 25, 2021

How Effective and Safe are Stimulant Medications for Older Adults?

How effective and safe are stimulant medications for older adults?

Older adults are at greater risk for cardiovascular disease. Psychostimulants may contribute to that risk through side effects, such as elevation of systolic blood pressure, diastolic blood pressure, and heart rate.

On the other hand, smoking, substance abuse, obesity, and chronic sleep loss - all of which are associated with ADHD - are known to increase cardiovascular risk, and stimulant medications are an effective treatment for ADHD.

So how does this all shake out? A Dutch team of researchers sets out to explore this. Using electronic health records, they compared all 139 patients 55 years and older at PsyQ outpatient clinic, Program Adult ADHD, in The Hague. Because a principal aim of the study was to evaluate the effect of medication on cardiovascular functioning after first medication use, the 26 patients who had previously been prescribed ADHD medication were excluded from the study, leaving a sample size of 113.

The ages of participants ranged from 55 from 79, with a mean of 61. Slightly over half were women. At the outset, 13 percent had elevated systolic and/or diastolic blood pressure, 2 percent had an irregular heart rate, 15 percent had an abnormal electrocardiogram, and 29 percent had some combination of these (a "cardiovascular risk profile"), and 21 percent used antihypertensive medication.

Three out of four participants had at least e comorbid disorder. The most common are sleep disorders, affecting a quarter of participants, and unipolar mood disorders (depressive or more rarely manic episodes, but not both), also affecting a quarter of participants.

Twenty-four patients did not initiate pharmacological treatment. Of the 89 who received ADHD medication, 58 (65%) reported positive effects, and five experienced no effect. Thirty-eight (43%) discontinued ADHD medication while at the clinic due to lack of effect or to side effects. The most commonly reported positive effects were enhanced concentration, more overview, less restlessness, more stable mood, and having more energy. The principal reasons for discontinuing medication were anxiety/depression, cardiovascular complaints, and lack of effect.

Methylphenidate raised heart rate and lowered weight, but had no significant effect on systolic and diastolic blood pressure. Moreover, there was no significant correlation between methylphenidate dosage and any of these variables, nor between methylphenidate users taking hypertensive medication and those not taking such medication. There was no significant difference in systolic or diastolic blood pressure and heart rate before and after the use of methylphenidate among patients with the cardiovascular risk profiles.

Systolic blood pressure rose in ten out of 64 patients, with two experiencing an increase of at least 20 mmHg. It descended in five patients, with three having a decrease of at least 20 mmHg. Diastolic blood pressure rose by at least 10 mmHg in four patients, while dropping at least 10 mmHg in five others.

The authors concluded "that the use of a low dose of ADHD-medication is well tolerated and does not cause clinically significant cardiovascular changes among older adults with ADHD, even among those with an increased cardiovascular risk profile. Furthermore, our older patients experienced significant and clinically relevant improvement of their ADHD symptoms using stimulants, comparable with what is found among the younger age group," and that "the use of methylphenidate may be a relatively safe and effective treatment for older adults with ADHD, under the condition that all somatic complaints and especially cardiovascular parameters are monitored before and during pharmacological treatment."

Yet they cautioned that "due to the observational nature of the study and the lack of a control group, no firm conclusions can be drawn as to the effectiveness of the stimulants used. ... Important factors that were not systematically reported were the presence of other risk factors, such as smoking, substance (ab)use, aspirin use, and level of physical activity. In addition, the response to medication was not systematically measured"

December 21, 2021

Can Neurofeedback Improve Executive Functions? New Meta-Analysis

New meta-analysis finds no improvement in executive functions from neurofeedback in children and adolescents

Meta-analysis show neurofeedback treatments resulted in no noticeable improvements in the working memory, response inhibition, or sustained attention of youth with ADHD.

Neurofeedback, also known as electroencephalogram (EEG) biofeedback, aims to help persons with ADHD train themselves to self-regulate patterns of brain activity associated with the disorder.

An example is theta-beta ratio frequency (TBR) training. Beta waves, with a frequency of 18 to 25 Hz, are associated with electrical activity when the brain is conscious or alert. Theta waves, with a frequency of 4 to 7 Hz, are associated with meditative, daydreaming, or drowsy states. In youths with ADHD, the theta to beta ratio tends to be elevated. TBR training seeks to reduce it.

Neurofeedback is often described as a promising emerging alternative or complement to pharmaceutical treatment. Previous meta-analyses have found neurofeedback can reduce symptoms of ADHD.

But what effect does it have on executive functions? A Thai research team based at Chiang Mai University conducted a comprehensive search of the peer-reviewed journal literature and identified ten studies with results suitable for meta-analysis.

A meta-analysis of all ten studies with a combined total, of 378 participants found no improvement whatsoever in response inhibition.

A second meta-analysis, of nine studies with a combined total of 349 participants, found no improvement in sustained attention.

Finally, a meta-analysis of three studies with a total of 121 participants likewise found no improvement in working memory.

In all three cases, there was no evidence of publication bias.

The authors concluded, "Results did not show the benefits of neurofeedback on executive functions assessed by neuropsychological tests."

December 15, 2021

ADHD and Poor Blood Sugar Management in Type-1 Childhood-onset Diabetes

Nationwide population study finds association between ADHD and poor blood sugar management in type-1 childhood onset diabetes

It is difficult enough for a typical child to manage type-1 diabetes. For a child that also has ADHD, with learning difficulties, attention and memory problems, and limitations in social communication, it can be all the more challenging to carry out the complex tasks necessary to maintain glycemic control (control of blood sugar levels) and avoid diabetic harm.

To explore the additional risk associated with ADHD among children with type-1 diabetes, an international research team used the Swedish national registers to conduct a nationwide population study. Sweden has a single-payer national health insurance system, and assigns unique personal identification numbers to all residents, making it easy to cross-reference through various population and health registers.

The team used the Swedish Diabetes Register to identify all individuals born in Sweden from 1973 onwards with childhood-onset type 1 diabetes diagnosed before age 18. They then restricted the cohort to those who had no diabetic complications at diagnosis and whose HbA1c values had been recorded within 5 years of diagnosis.

Also known as the glycated hemoglobin test, HbA1c is an indicator of the average blood sugar (glucose) level over the past three months. When glucose builds up in the blood, it binds to the hemoglobin in red blood cells. The HbA1ctest measures bound glucose. Since red blood cells live for about 3 months, the test shows the average blood glucose over that period.

The team also searched for records of diabetes-related kidney damage (nephropathy) and damage to the retina (retinopathy). Diabetic retinopathy is the leading cause of blindness among working-age adults.

The nationwide cohort consisted of 11,326 Swedish youths diagnosed with type-1 diabetes, of whom 415 (3.7%) were also diagnosed with ADHD.

Poor glycemic control, defined as mean HbA1c greater than 8.5%, was found in 38% of those with ADHD, twice the 19% found in those without neurodevelopmental disorders. After adjusting for confounders(sex, age at diabetes diagnosis, year of birth and year of diabetes diagnosis, another psychiatric morbidity, parental highest education level, parental psychiatric morbidity, smoking status, mean BMI [body mass index], and mean systolic and diastolic blood pressure), those with ADHD were 2.3 times as likely to have poor glycemic control.

Patients with ADHD were also almost twice as likely to suffer kidney damage, after adjusting for sex, age at diabetes diagnosis, year of birth, year of diabetes diagnosis, another psychiatric morbidity, parental highest education level, parental psychiatric morbidity, mean HbA1c levels, mean BMI, systolic and diastolic blood pressure, and smoking status.

After the same adjustments, patients with ADHD were found to be a third (33%) more likely to suffer retinal damage.

The team concluded, "childhood-onset type 1 diabetes patients with neurodevelopmental disorders, especially those with ADHD or intellectual disability, are more prone to poor glycemic control and a higher risk of chronic diabetic complications compared with those without neurodevelopmental disorders.

Further longitudinal studies with a more comprehensive evaluation of diabetes management and molecular data are needed to provide insight into potential mediators in the association between comorbid neurodevelopmental disorder and diabetes complications in type 1 diabetes."

December 9, 2021

Parents of Children With ADHD at Higher Risk for Traumatic Injury

Nationwide population study finds higher risk of traumatic injury among parents of children with ADHD

Previous population studies have shown that children with ADHD have a much higher risk of traumatic injuries than their normally developing peers, and that such risk can be greatly reduced with methylphenidate treatment.

But what about the parents of children with ADHD? How does their risk compare with that of parents of normally developing children?

Taiwan has a single-payer public health insurance system that maintains comprehensive healthcare records of virtually every resident.

A Taiwanese research team availed itself of the Taiwan Maternal and Child Health Database, which covers 99.8% of all births, to identify 81,401 fathers and 87,549 mothers who had at least one offspring with ADHD and 1,646,100 fathers and 1,730,941 mothers with no offspring with ADHD.

The team determined children's ADHD status based on either an inpatient diagnosis or four or more  diagnoses.

It looked for parental traumatic injuries including burn injury, fracture, and traumatic brain injury.

To address covariates, it adjusted for age, urbanicity, low-income level, and competing risk of death.

Adjusted for those covariates, parents of children with ADHD were 20% more likely to suffer bone fractures, 27% more likely to have traumatic brain injuries, and 30% more likely to have burn injuries requiring medical treatment than parents of normally developing children.

The elevated risks were significant across the board, but roughly twice as much s for mothers as for fathers of children with ADHD - up 30% vs 15% for bone fractures, up 35% vs 23% for burn injuries, and up 45% vs 21% for traumatic brain injuries.

The authors noted that ADHD is highly heritable and that the findings may in part point to undiagnosed adult ADHD.

Another contributing factor, they suggested, is that "studies have revealed that a high proportion of parents having children with ADHD experience depression and anxiety. Stress-related negative emotions (depression and anxiety) were shown to cause loss of concentration, thereby increasing the likelihood of accidental events such as traffic accidents and contributing to the increased risks of traumatic injury among parents of children  ADHD."

The much-higher elevated risk for mothers seems to support this hypothesis, because mothers continue to be the principal caregivers in Taiwan, and are thus more exposed to the behaviors of their children. The authors cited a study indicating that "diagnosis of ADHD for children was reported to be a predictor of increased caregiver burden."

They concluded, "Given that knowledge is fundamental to act, it is essential to educate the parents of children with ADHD on the increased risk of traumatic injuries they may have. ... The need for behavioral and pharmacological intervention in parents of children with ADHD should be evaluated, especially in the parents with undiagnosed ADHD or sub-threshold ADHD symptoms. It deserves further prospective studies with longer follow-up periods to explore whether undiagnosed ADHD, care burden of parents, and children's aggressive behaviors contribute to the increased risks of traumatic injuries in parents of children with ADHD."

December 7, 2023

Safety of Long-term Methylphenidate Treatment of Adults with ADHD

Safety of long-term methylphenidate treatment of adults with ADHD

The Comparison of Methylphenidate and Psychotherapy in adult ADHD Study (COMPAS) was a prospective, randomized multicenter clinical trial, comparing methylphenidate (MPH) with placebo in combination with cognitive-behavioral group psychotherapy or (GPT) individual clinical management (CM), the latter two being active controls. This was a year-long trial.

The German study team randomly assigned 433 participants with adult ADHD to each of the four study groups. As this was a 2 x 2 matrix trial, each study group included both one pharmacological intervention (MPH or placebo) and one psychological intervention (GPT or CM).

GPT included mindfulness training, skills for stress management, emotion regulation, and time management as well as behavioral analyses. CM sessions focused on participants' current concerns and medication.

As is usual in such trials, the number of participants decreased throughout the study as some individuals dropped out. At 13 weeks, 337 participants were still taking their study medication.

Both MPH and placebo were started at 10 mg doses, then up-titrated depending on clinical response. After 13 weeks, the mean MPH dose had risen to 50 mg, and the mean dose of placebo to 58 mg.


Among those taking MPH, 96 percent of participants reported at least one adverse event. Among those on placebo, the equivalent figure was 88 percent.

The principal adverse events occurring significantly more frequently in the MPH group were decreased appetite (22 vs. 3.8 %), dry mouth (15 vs. 4.8 %), palpitations (13 vs. 3.3 %), gastrointestinal infection (11 vs. 4.8 %), agitation (11 vs. 3.3 %), restlessness (10 vs. 2.9 %), excessive sweating, rapid heartbeat, and weight decrease (all 6.3 vs. 1.9 %).

The only adverse event that occurred significantly more frequently in the placebo group was a temporary loss of consciousness caused by a fall in blood pressure (2.4 vs. 0%).

Serious adverse events were infrequent in both groups, affecting 7.3 percent of those in the MPH group and 4.3 percent of those in the placebo group. The difference between groups was not statistically significant. There were no deaths.

While patients on MPH lost an average of 1.2 Kg during the year, those on placebo remained constant (gained 0.3 Kg). Changes in blood pressure were negligible in both groups. Average heart rate rose by 3 beats per minute in the MPH group, versus a 1 beat per minute decline in the placebo group. There were no significant differences in clinically relevant electrocardiogram abnormalities between the two treatment groups.

Turning to psychological interventions, 90 percent of participants in the GPT group and 94 percent in the CM group experienced at least one adverse event. Differences between the two groups were not statistically significant. Serious adverse events occurred in 3.9% of the GPT participants and 7.7 percent of the CN participants, but again the difference between groups was not statistically significant. There were no clinically relevant changes in weight, blood pressure, or heart rates in these groups throughout the study.

The study team found no modulating effects of either form of psychological treatment on the distribution of adverse events under MPH and placebo treatment.

The authors concluded, "adverse events were found more frequently in patients receiving MPH compared to placebo and were mostly attributable to the centrally stimulating and sympathomimetic action of MPH, including agitation, restlessness, dry mouth, decreased appetite, palpitations, tachycardia [rapid heartbeat], and hyperhidrosis [excessive sweating]. About these adverse events, a causal relationship with MPH seems likely, supported by both the pharmacological effects of MPH as well as previous safety data. ... It is important to note that patients receiving MPH in COMPAS significantly profited from the medication about the reduction of ADHD symptom load, thus the risks of adverse events have to be weighed against the clear benefits. ... Premature termination of MPH due to an adverse event as major reason occurred in less than 10 % of patients and was not statistically significantly different from placebo."

November 21, 2021

Supplements Helping ADHD Symptoms: Anecdotal or Proven?

Meta-analysis claims effectiveness of multi-nutrient supplements in treating ADHD, but reports inconsistent results and has methodological shortcomings

A recently published meta-analysis compared the treatment of ADHD with multi-nutrient supplements versus placebo.

Children received either placebo or Daily Essential Nutrients(Vit A 384 IU, Vit C 40 mg, Vit D 200 IU, Vit E 24 IU, Vit K 8 μg, B1 4 mg, B21.2 mg, B3 6 mg, B6 4.67 mg, B9 50 μg, B12 60 μg, B7 72 μg, B5 2 mg, Ca 88 mg, Fe 0.92 mg, P 56 mg, I 13.6 μg, Mg 40 mg, Zn 3.2 mg, Se 13.6 μg, Cu 0.48 mg, Mn0.64 mg, Cr 41.6 μg, Mo 9.6 μg, P 16 mg. Proprietary blend: Choline bitartrate, Alpha-lipoic acid, Inositol, Acety-l-carnitine (as acetyl-L-carnitine hydrochloride), Grape seed extract, Ginkgo biloba leaf extract, Methionine (asL-methionine hydrochloride), Cysteine (as N-acetyl-L-cysteine), Germanium sesquioxide (as chelate), Boron, Vanadium, Lithium orotate, Nickel. Other ingredients: Cellulose glycine 45 mg, Citric acid 26.814 mg, Magnesium stearate24 mg, Silicon dioxide 20 mg).

Adults received either placebo or EMP+ (Vit A 5760IU, Vit C 600 mg, Vit D 1440 IU, Vit E 360 IU, B1 18 mg, B2 13.5 mg, B3 90 mg,B5 21.6 mg, B6 36 mg, B9 1440 μg, B12 900 μg, Biotin 1080 μg, Pantothenic acid21.6 mg, Ca 1320 mg, Fe 13.74 mg, P 840mg, I 204 μg, Mg 600 mg, Zn 48 mg, Se204 μg, Cu 7.2 mg, Mn 9.6 mg, Cr 624 μg, Mo 144 μg, K 240 mg, Germaniumsesquioxide 20.7 mg, B 2400 μg, V 1194 μg, Ni 29.4 μg, Choline bitartrate 540mg, DL-phenylalanine 360 mg, Citrus bioflavonoids 240 mg, Inositol 180 mg,Glutamine 180 mg, L-methionine 60 mg, Gingko biloba 36 mg, grape seed extract45 mg).

Using the Global Assessment of Functioning (GAF) scale for adults, and the Children's Global Assessment Scale (CGAS) for children, the study team reported moderate improvements in overall functioning from the use of the supplements. GAF and CGAF are used by mental health clinicians and physicians to rate subjectively the social, occupational, and psychological functioning of an individual.

Yet no significant improvements were found for either clinician-rated or observer-rated ADHD Change Scores.

Moreover, the positive finding was compromised by a series of methodological shortcomings:

·        It was just barely a meta-analysis, involving only two studies.
·        The combined number of participants in the two studies was small, 173, consisting of 93 children in one study and 80 adults in the other.
·        Both studies had the same lead author, Julia J. Rucklidge, who was also a member of the meta-analysis team.

With only two studies, there was no way to evaluate publication bias.

October 25, 2023

Meta-analysis Finds Narrative Language Impairment in Youths with ADHD

Meta-analysis Finds Narrative Language Impairment in Youths with ADHD

Youths with ADHD are known to be more prone to language problems when compared with typically developing peers. To what extent does that affect their ability to share a narrative with others?

A Danish research team conducted a systematic review and meta-analysis of the peer-reviewed medical literature to explore this question. They stressed that this ability is important because "a narrative is a genre of discourse - a form of social communication used to derive meaning from experiences and to construct a shared understanding of events. In other words, it is the fundamental ability of orally producing a coherent story." They focused on the production of narratives rather than comprehension.

Studies had to have a minimum of 10 participants. They had to compare aspects of oral narrative production in children and adolescents with either a formal ADHD diagnosis or a score above a clinical cut-off on a validated ADHD rating scale to a control group of typically developing youths. Youths with confirmed autism spectrum disorder (ASD) or language impairment diagnoses were excluded. There were no constraints on IQ.

The team found sixteen studies with a combined total of 1,015 youths that met these criteria and were suitable for meta-analysis.

They examined seven aspects of oral narrative production:

·        Coherence: A story structure that is logical and easy to follow in cause and sequence. There is a clear beginning, middle, and end. There are goals, attempts, and outcomes. A meta-analysis of nine studies with a combined total of 750 participants found youths with ADHD less coherent than their typically developing peers, with a medium effect size. There was virtually no between-study heterogeneity and no sign of publication bias.
·        Cohesion: This ensures referencing of events and characters in a manner that enables the listener to grasp how characters, events, and ideas in a story are related. Ambiguous or contradictory references get in the way of this. A meta-analysis of eight studies with a combined total of 501 participants found youths with ADHD showed less cohesion than their typically developing peers, with a medium effect size. Again, with virtually no between-study heterogeneity, and no sign of publication bias.
·        Disruptions: These can be sequence errors, misinterpretations, embellishments, or confabulations - fabricating imaginary experiences as compensation for loss of memory. A meta-analysis of six studies with 389 participants found youths with ADHD had more disruptions than their typically developing peers, with a small-to-medium effect size. There was virtually no between-study heterogeneity and no sign of publication bias.
·        Fluency: Best explained in terms of errors that interfere with this quality, such as false starts, repeating words or sentences, and abandoning sentences without completing them. A meta-analysis of four studies with 220 participants found no difference in fluency between youths with ADHD and their typically developing peers.
·        Production: This is a measure of output -overall length of the story, number of sentences, number of words. After adjusting for evidence of publication bias, a meta-analysis of twelve studies with 645 participants found no difference here.
·        Syntactic complexity: This includes the extent of vocabulary and the use of proper grammar. A meta-analysis of six studies with 272 participants found youths with ADHD displayed less syntactic complexity than their typically developing peers, with a small-to-medium effect size. There was virtually no between-study heterogeneity and no sign of publication bi
·        Internal state language: References to perceptions, thoughts, beliefs, and feelings. There were only two studies with 130 participants, so no meta-analysis was performed.

The authors concluded, "the results from the current meta-analysis suggest that children with ADHD have impairments in their narrative language. In particular, children with ADHD produce narratives that are less coherent, less cohesive, less syntactically complex, and include more disruptive errors than typically developing children do."

December 4, 2023

Safety and Efficacy of Long-term Use of Guanfacine for Adults with ADHD

Safety and efficacy of long-term use of guanfacine for adults with ADHD

Guanfacine extended-release(GXR) is a non-stimulant α2A-adrenergic receptor agonist, approved worldwide for ADHD in children and adolescents.

A Japanese research team set out to explore the long-term administration of once-daily GXR in adults with ADHD over a year of treatment. Their primary objective was to evaluate the safety, and the secondary objective was to evaluate efficacy.

This was an open-label trial. Open-label trials are the opposite of double-blind trials. In a double-blind trial, neither the researchers nor the participants know what treatment they participants are receiving. In an open-label trial, on the other hand, both the researchers and participants know what treatment the participant is receiving, which can introduce significant bias. These studies are therefore at the lowest rung in the evidentiary base.

It is worth noting, however, that the risk of bias would be primarily for efficacy, and the primary aim of the trial was to evaluate safety.

The trial was funded by the manufacturer, but preregistered, a way of assuring that results would be released regardless of the outcome.

The study population consisted of 191 ADHD patients 18 and older at 71 locations in Japan. There was no control population. The 50-week flexible titrated dosing treatment period was followed by a 2-week period over which doses were gradually reduced, and then a one-week follow-up period. That means the trial covered an entire year. Of the enrolled patients, 67 dropped out, mostly due to adverse events, leaving 124 patients after the trial.

A total of 830 treatment-emergent adverse events (TEAEs) were reported by 180 patients. One in five patients (34)discontinued treatment due to adverse events. The most commonly reported adverse events were somnolence, thirst, nasopharyngitis, decreased blood pressure, postural dizziness, bradycardia (abnormally slow heartbeat), malaise, constipation, and dizziness. Except for nasopharyngitis, all were considered related to the medication. There were two serious adverse events, one unrelated to the medication, the other a supraventricular tachycardia (abnormally fast heart rhythm arising from improper electrical activity in the upper part of the heart) in a patient simultaneously medicated for a preexisting condition. The patient recovered after treatment and discontinuation of GXR.

The main TEAEs resulting in Discontinuation were somnolence (nine patients), blood pressure reduction (eight patients), malaise (six patients), and bradycardia (four patients, with only one case considered severe), and postural dizziness (three patients) or dizziness(three patients).

Significant reductions in ADHD scores and improvements in executive functioning were measured across the study population following a year's GXR treatment. Again, this was not the primary aim of the trial, and double-blinded randomized controlled trials are the gold standard.

The authors concluded that "there were no new or unexpected safety concerns" and "patients who received dose-optimized GXR had improvements in multiple aspects of ADHD, including symptoms, QoL [Quality of Life], and executive functioning," but acknowledged, "There was a potential for observer bias because of the open-label nature of the study, and the findings may not be representative of real-world settings because patients with psychiatric or cardiovascular comorbidities, which are common in patients with ADHD, were excluded. In addition, there was a potential bias favoring safety and efficacy for continuing patients because those who discontinued owing to adverse events or lack of efficacy were not eligible for inclusion."

October 23, 2023

Meta-analysis Finds Association Between Postnatal Secondhand Smoke and ADHD

Meta-analysis finds association between postnatal secondhand smoke and ADHD

Secondhand smoke (SHS) is tobacco smoke inhaled by nonsmokers sharing enclosed spaces with smokers. It contains well over two hundred toxic chemicals, including some toxic metals known to cause serious harm to humans. It is among the most common indoor air pollutants worldwide, with roughly two in five children exposed.

Until now, studies have focused primarily on maternal smoking before childbirth. A Chinese research team set out to explore what, if any, association there might be between childhood exposure to SHS and ADHD. They conducted a comprehensive search of the peer-reviewed literature and identified nine studies with a combined total of over a hundred thousand participants that looked for such effects. The studies were carried out in the United States, Germany, Spain, and the Republic of Korea.

Merging these studies into a meta-analysis, the team found that children exposed to secondhand smoke were 60 percent more likely to develop ADHD. The same overall pattern held true on all three continents.

A further meta-analysis of four of the studies with over 12,000 participants found children exposed to secondhand smoke were 33% more likely to exhibit conduct problems.

The authors concluded, "The results of our meta-analysis suggest that postnatal exposure to SHS may be associated with ADHD in children. Exposure to SHS can also lead to a variety of adverse behavioral outcomes in children. Therefore, parents should stop smoking to create a good growing environment for their children. Further prospective studies should fully adjust for potential confounding factors to determine whether there is a causal relationship between SHS and ADHD."

December 4, 2023

Why are children born in August more likely to be diagnosed with ADHD?

Why are children born in August more likely to be diagnosed with ADHD?

Taiwan's single-payer National Health Insurance system encompasses its entire population, and it's National Health Insurance Research Database tracks all medical claims in the system. That makes it easy to conduct nationwide population studies.

Two Taiwanese research teams availed themselves of that database to explore in-depth a surprising relationship between the birth month of children and rates of ADHD diagnosis.

In principle, the two should be unrelated. The likelihood of diagnosis should be the same regardless of the month a child is born. But the data are clear that this is not so. Children born late in summer are the most likely to be diagnosed with ADHD, and those in autumn are the least likely.

Using a nationwide database of over 29 million persons, one of the teams (Hsu et al.) found that children born in April were 6% more likely to be diagnosed with ADHD than the year-round mean, those in May 12% more likely, those in June 20% more likely, and those in July and August well over 25% more likely.

Conversely, children born in September were 19% less likely to be diagnosed with ADHD than the year-round mean, followed by a gradual increase in likelihood with each succeeding month until the following September.

The second team (Chen et al.) analyzed some 9.5 million children and adolescents in the same reserch database, and found that those born in August were 67% more likely to be diagnosed with ADHD than those born in September, after adjusting for age, sex, residence, and income. August births were also almost twice as likely (80% more likely) as September births to be on long-term treatment with ADHD medications.

The first team also performed a meta-analysis of eleven studies with a combined total of over 580,000 participants in North America (the U.S. and Canada), Europe (U.K., Germany, Norway, Sweden, Denmark), Asia (China, Taiwan, South Korea), and Oceania (Australia). Children born in the summer (June through August) were 13% more likely to be diagnosed with ADHD than the year-round mean, whereas those born in autumn were 13% less likely to be diagnosed with ADHD. This confirms that this pattern is not confined to Taiwan. It is worldwide.

Note carefully that the sharp discontinuity between August and September corresponds with the break-of point that decides which children get assigned to which school class. Anyone who turns a certain age by the start of the school year in September is included in the class associated with that age, whereas those turning the same age later are held back in the following class. That means that in any given class, those born in September are the oldest children and those born in August the youngest.

As signaled earlier, the likelihood of an ADHD diagnosis should be independent of something as obviously arbitrary as a birth month. That suggests there may be an unconscious bias trending against younger students when it comes to diagnosis.

Chen et al. concluded, "The effect of relative age on diagnoses and prescriptions was determined to last from childhood to adolescence but attenuated with age. Relative age is an indicator of brain maturity in cognition, behavior, and emotion and may thus play a critical role in the likelihood of being diagnosed as having childhood mental disorders and subsequently being prescribed psychotropic medication. Therefore, clinicians should consider the relative age effect in the childhood mental health care context."

September 14, 2023

Associations Between ADHD and Suicidality in Canadian Cohort Study

Ambiguous associations between ADHD and suicidality in a Canadian cohort study

The National Longitudinal Survey of Children and Youth is a prospective cohort of Canadian children followed from childhood to early adulthood. It is considered nationally representative, except for children living on First Nations (indigenous) reserves, in institutions, and in remote regions. Keep in mind that suicide rates among indigenous youth are way higher than in the general population.

The initial cohort included 8,698 participants aged 7- 11 years, of which 6,465 had to be excluded for lack of answers to questions on suicide attempts, leaving 2,233 participants. Again, by comparison with the excluded group, these participants were less likely to be from higher-risk backgrounds, including having a mother who did not complete high school or coming from low-income families.

The share of adolescents who attempted suicide in the previous year increased from 3.6% at ages 12-13 years to 5.6% at ages 14-15 years, then gradually declined to 1% of young adults at ages 22-23 years.

The overwhelming majority (96%)reported never attempting suicide. One in fifty (2%) reported suicide attempts limited to adolescence, and another one in fifty reported suicide attempts persisting into adulthood.

The study team performed a multivariable regression model examining the contributions of sex and ten risk factors, including various psychiatric disorders, for suicidality. One of those risk factors was ADHD, split into two subcategories: symptoms at 10-11 years, and symptoms at 12-13 years. Those in the former group were twice as likely -for each standard deviation increase in symptoms - as those without such symptoms to report suicide attempts persisting into adulthood versus never attempted. But they were no more likely to report adolescence-limited attempts versus never-attempted, or attempts persisting into adulthood versus adolescence-limited. Furthermore, there were no significant associations between ADHD symptoms at 12-13 years and any of the three foregoing categories.

The authors acknowledged, "despite the large sample size, the number of individuals who attempted suicide was low, limiting the statistical power ..."

September 29, 2023

Is There an Association Between Perfluoroalkyl Substances (PFAS)-exposure in Infancy and ADHD?

Is There an Association Between Perfluoroalkyl Substances (PFAS)-Exposure in Infancy and ADHD?

Although there are numerous kinds of perfluoroalkyl substances (PFAS), the primary ones used in the manufacture of fluoropolymers are perfluorooctanesulfonic acid (PFOS) and perfluorooctanoic acid (PFOA). Because of their strong water-repelling properties, fluoropolymers are used in stain repellents, polishes, paints, and other coatings, as well as in water-resistant outdoor clothing. They are long-lasting and therefore both pervasive in the home and environment and subject to accumulation in our bodies, especially in urbanized and industrialized areas. These substances can be passed from mother to child both through the placenta and through breastfeeding.

With support from the European Union, a large international team of European and North American researchers set out to investigate possible associations between early-life exposure to PFOS and PFOA and subsequent ADHD. They performed a meta-analysis on nine European population studies encompassing 4,826 mother-child pairs.

Participants were restricted to live-born single births with data on concentrations of PFOS and/or PFOA, and available information on ADHD diagnosis or symptoms.

Because a) some studies looked at maternal serum/plasma, others at maternal breast milk; b) timing of sample collection varied (first trimester, delivery); and c) children's levels during the first two years of life were unavailable (ethical constraints limit drawing blood samples from infants), the team used a validated pharmacokinetic model of pregnancy and lactation to estimate pre-and postnatal concentrations of PFASs in offspring.

The team adjusted for seven potential confounders: maternal pre-pregnancy body mass index, maternal age at delivery, maternal education, maternal smoking, number of previous children, duration of breastfeeding, and child sex.

With these adjustments, no association was found between estimated exposures to either PFOS or PFOA at birth, at three months, and at two years and subsequent diagnosis or symptoms of ADHD. While the raw data showed slightly higher odds for girls than for boys to develop ADHD with identical exposures, the differences were statistically non-significant.

November 27, 2023

Does Sugar Actually Worsen ADHD Symptoms? A Meta-Analysis

Meta-analysis finds no association between sugar consumption and ADHD, but a possible link with sugar-sweetened beverages

There's a widespread, but so far unsupported, popular belief that sugar consumption, and sugar-sweetened beverages, in particular, trigger symptoms, especially hyperactivity, in youth.

Given the steep rise of sugar consumption by youth, what evidence is there of a link to ADHD?  

An Iranian team of researchers carried out a comprehensive search of the peer-reviewed literature on this subject. It identified seven studies - two cross-sectional, two case-control, and three prospective " with a combined total of over 25,000 participants that were amenable to meta-analysis. The studies spanned the globe, including the United States, Brazil, Taiwan, the U. K., Spain, and Norway.

Using a fixed-effects model, they found a tiny 7.5% increase in ADHD associated with sugar consumption. With a random-effects model, that rose to a 22% increase. But correcting for publication bias with a trim-and-fill adjustment removed any evidence of an association (p = 0.8).

Even without adjusting for publication bias, subgroup analysis found no evidence of an association with sugar consumption per se.

On the other hand, two studies that looked exclusively at sugar-sweetened beverages reported an 80% increase in the odds of ADHD. There was no way to evaluate publication bias for just two studies. Furthermore, two studies are insufficient for a proper meta-analysis.

There are two conclusions to be drawn from this meta-analysis: 1) It reinforces previous findings of no significant association between sugar consumption and ADHD; 2) It suggests it would be worth conducting more studies, specifically focusing on sugar-sweetened beverages.

November 13, 2023

How prevalent is ADHD in older adults?

How prevalent is ADHD in older adults?

An international team of researchers recently published the first meta-analysis of studies examining the prevalence of ADHD in older adults, with a particular focus on those fifty and older. They also looked at rates of treatment.

Since clinical evaluations a reconsidered the gold standard in diagnosing ADHD, and validated rating scales are considered more of a preliminary screening tool, the team distinguished between the two and ran two separate meta-analyses:

·        Using validated ADHD rating scales. Combining nine studies with just over 32,000 participants, the team reported a prevalence of 2.2 percent. However, since the studies were not uniform in fixing the minimum end of their age ranges, constraining the results to persons 50 and older lowered the prevalence to 1.5 percent.

·        Using clinical diagnoses. Combining seven studies with 11.7 million participants, they found a crude prevalence of 0.23 percent, which, after removing persons under 50, was adjusted to 0.19 percent. Limiting the results to the use of national registries further reduced the prevalence to 0.14 percent.

That means there's an order of magnitude (tenfold) difference between the two estimates of prevalence.

Recognizing that clinical diagnoses are the preferred means of diagnosis, the authors wrote, "methodological aspects need to be considered when interpreting the gap between the pooled prevalence estimates based on different assessment methods. The estimates from studies based on research diagnosis [ADHD rating scales] may overestimate the prevalence of ADHD in older adults. ... Thus, screening assessment tools for ADHD should only be used as the first step of a more comprehensive clinical ADHD assessment."

On the other hand, the authors also see an indication "that clinicians, to some extent, might fail to recognize and properly treat ADHD symptoms in older adults. Clinical presentation of ADHD may change with age, with inattentive symptoms becoming more prevalent than hyperactivity and impulsivity."

The team also performed a third meta-analysis, to look at ADHD pharmacological treatment rates among older adults. For this one, they pooled four studies encompassing over 9.2 million persons. After constraining the results to those fifty and older, they found a prevalence of only 0.02%. This points to a wide gap between rates of diagnosis and rates of treatment, even after noting that only one of the studies included data on non-pharmacological treatment.

November 1, 2023

Certain Stimulants May Reduce Risk of Intentional Abuse and Harm

Modified release stimulants reduce risk of intentional abuse and harm, based on data from U.S. poison control centers

Modified release (MR) formulations of ADHD stimulant medications simplify adherence over immediate-release (IR) formulations, by only requiring a single dosing per day. They are also intended to reduce diversion to nonmedical usage and the development of drug abuse or dependency. Is there evidence they deliver on this promise?

There are 55 poison control centers distributed throughout the United States, and they all report through the National Poison Data System (NPDS).

A pair of researchers used the NPDS to obtain all 15,796 single-substance MR ingestion and single-substance 23,418 IR ingestion reported to poison control centers over the eleven years from January 1, 2007, through December 31, 2017. The medications were either amphetamine or methylphenidate-based.

IR ingestion was more commonly associated with more serious outcomes than were MR ingestion. No deaths were reported from MR stimulant ingestion, versus three deaths (a rate of one in 7,800 reports) from IR stimulant ingestion. While there were no observed differences between youth MR and IR ingestion about admission to critical care units, adult IR ingestion was more commonly admitted to a critical care unit than was adult MR ingestion. Moreover, adults were more commonly admitted to critical care units for both MR and IR ingestion than were youths.

Among youths, the vast majority of MR ingestion was unintentional, with only one in eleven attributed to intentions of suicide. Among adults, however, almost half were intentional, with just over a quarter attributed to intentions of suicide, and another one in six to intentional misuse.

Turning to IR ingestion, the vast majority were again unintentional among youths, with less than one in twelve attributed to suspected suicide attempts. But among adults, the majority were intentional, with almost one in three attributed to suspected suicide attempts, plus another one in five to intentional misuse.

More than four out of five IR ingestion among both youths and adults were of amphetamine medications. For MR ingestion, methylphenidate was most common in youths and amphetamine medications in adults, but only by slight margins.

The most commonly reported symptoms in adults and youths alike for both IR and MR ingestion were agitation, abnormally rapid heart rates, and high blood pressure.

The authors concluded, "More serious outcomes were associated with advancing age, intentional ingestion, and IR preparations. Higher rates of hyperadrenergic symptoms (tachycardia, agitation, and hypertension) were observed with IR ingestion."

On balance, this suggests MR formulations are safer, but both formulations are subject to abuse by a small minority of users.

October 18, 2023

Children with ADHD have considerably greater odds of being victimized in reported sexual crimes

Children with ADHD have considerably greater odds of being victimized in reported sexual crimes

Youths with disabilities face varying degrees of social exclusion and mental, physical, and sexual violence.

A Danish researcher used the country's extensive national registers to explore reported sexual crimes against youths across the entire population. Of 679,683 youths born from 1984to 1994 and between the ages of seven and eighteen, 8,039 (1.2 percent) were victims of at least one reported sex crime.

The sexual offenses in question included rape, sexual assault, sexual exploitation, incest, and indecent exposure. Sexual assault encompassed both intercourse/penetration without consent or engaged in with a youth not old enough to consent (statutory rape).

The study examined numerous disabilities, including ADHD, which was the most common one. It also performed a regression analysis to tease out other covariants, such as parental violence, parental inpatient mental illness, parental suicidal behavior or alcohol abuse, parental long-term unemployment, family separation, and children in public care outside the family.

In the raw data, youths with ADHD were 3.7 times more likely to be a victim of sexual crimes than normally developing youths. That was roughly equal to the odds for youths with an autism spectrum disorder or mental retardation, but considerably higher than for blindness, stuttering, dyslexia, and epilepsy (all roughly twice as likely to be victims of such crimes), and even higher than for the loss of hearing, brain injury, or speech or physical disabilities.

Looking at covariate, family separation, having a teenage mother, or being in public care almost doubled the risk of being a victim of sexual crimes. Parental violence or parental substance abuse increased the risk by 40 percent, and parental unemployment for over 21 weeks increased the risk by 30 percent. Girls were nine times more likely to be victimized than boys. Living in a disadvantaged neighborhood made no difference, and living in immigrant neighborhoods actually reduced the odds of being victimized by about 30 percent.

After adjusting for other risk factors, youths with ADHD were still almost twice as likely to be victims of reported sex crimes than normally developing youths. All other youths with disabilities registered significantly lower levels of risk after adjusting for other risk factors: for those who were blind, 60 percent higher risk; for those with autism, hearing loss, or epilepsy, 40 percent higher risk. Communicative disabilities - speech disability, stuttering, and dyslexia - actually turned out to have protective effects.

This points to a need to be particularly vigilant for signs of sexual abuse among youths with ADHD.

September 28, 2023

How Acupuncture Compares with Methylphenidate for Reducing ADHD Symptoms

Meta-analysis compares efficacy of acupuncture with methylphenidate for reducing ADHD symptoms

A team of Taiwanese researchers conducted a comprehensive search of the peer-reviewed literature to identify all randomized controlled trials (RCTs) performed to date exploring the efficacy of acupuncture treatment (AT) in reducing ADHD symptoms. They found ten studies with a combined total of 876 participants that met their search criteria. Seven were performed in China, one in South Korea, one in Iran, and one in the U.S. All involved youths, ranging from ages 3 to 18.

All required either a DSM-IV or DSM-V diagnosis of ADHD for inclusion. The controls varied. One used waitlist. Eight compared acupuncture treatment with methylphenidate treatment, with dosages varying from as little as 10-20 mg/day to 1,020 mg/day and 1,854 mg/day. Only one study was double-blind, meaning that both participants and investigators were blinded as to who was getting which treatment. It is of course essentially impossible to blind participants in RCTs involving AT unless sham-At is used as a control. Only one RCT compared AT with sham-AT, and it was not used in either meta-analysis.

Keeping these limitations in mind, a meta-analysis of the eight studies with 716 participants that compared AT with MPH found AT to be more than twice as effective in reducing ADHD symptoms as MPH. Heterogeneity between studies was low, with no sign of publication bias.

However, none of these studies reported ADHD rating scale scores, an additional major limitation. Instead, because outcome measurements varied across RCTs, the authors relied on "effective rate" (ER): The evaluation was divided into cured, markedly effective, effective, and ineffective. We merged the number of "cured," "markedly effective," and "effective" patients to be divided by the sample size to calculate the proportion of subjects who experienced at least some improvement in their ADHD symptoms in the ER.

On the other hand, a meta-analysis of three studies with 232 participants compared the effects of AT and MPH on actual hyperactivity scores and found MPH was much more effective than AT. Homogeneity was moderate, again with no sign of publication bias.

The author cautioned, "The quality of the evidence was low for the ER assessment because of the selection, performance, and detection biases. For hyperactivity scores, the quality of evidence was very low because of the selection and performance biases and significant heterogeneity." Due to the various limitations, they concluded, "AT may be more effective than methylphenidate for the treatment of ADHD in children and adolescents," but "firm conclusions still can not be drawn."

November 15, 2023

Methylphenidate May Reduce Risk of Burn Injury in Children with ADHD

Methylphenidate reduces risk of burn injury in children with ADHD in nationwide population cohort study

Children with ADHD are at higher risk of getting severe burns than normally-developing children. Burn injuries can be traumatic, imposing physical, psychological, and economic burdens on children, their families, and society. Methylphenidate is known to be effective in reducing ADHD symptoms. Can it also reduce the risk of burn injuries?

A team of Taiwanese researchers collaborating with two British researchers explored that question by looking at a nationwide population cohort. Taiwan has a single-payer national health insurance system that includes the entire population (99.6 percent coverage). Using Taiwan's National Health Insurance Research Database(NHIRD), they identified over 90,000 youths under 18 years old with a diagnosis of ADHD. Youths who had burned injuries before diagnosis were excluded. ADHD youths were further divided into three groups: those not prescribed methylphenidate (over 22,000), those prescribed methylphenidate for less than 90 days (over 17,500), and those prescribed methylphenidates for 90 days or more(over 50,000).

Because methylphenidate is the only approved stimulant in Taiwan, it was the only stimulant analyzed in this study. Atomoxetine, a non-stimulant, is also approved in Taiwan, but only for those whose, outcomes with methylphenidate are suboptimal. It was only used by 4 percent of those on ADHD medication, and generally after prior use of methylphenidate, so there was no way to evaluate its effectiveness. Among ADHD youths not on methylphenidate, the proportion who got burn injuries was 6.7 percent. That dropped to 4.5 percent for those medicated for under 90 days, and to 2.9 percent for those on longer-term medication.

Calculations indicated that half of all burn injuries could have been prevented if all youths had been on methylphenidate. After adjusting for multiple confounders - seizure, intellectual disability, autism, conduct disorder, opposition defiant disorder, anxiety, depression, and psychotropic use (benzodiazepine, Z-drugs, antipsychotics, and antidepressants) that taking methylphenidate for any length of time was 38 percent less likely to suffer burn injuries. Moreover, longer-term medication had a greater beneficial effect. Those taking methylphenidate for under 90 days were 30 percent less likely to get burn injuries, whereas those taking it for 90 or more days were less than half as likely to get burn injuries as those not on methylphenidate.

The authors emphasized, "This nationwide population-based study has several strengths. First, the nationally representative sample was substantial and minimized selection bias. Second, patients with ADHD were identified through physician-based diagnoses. Third, all MPH [methylphenidate] prescriptions are recorded in the NHIRD, avoiding misclassification bias. Also, by excluding burn injuries before ADHD diagnosis, the reverse causal relationship between ADHD and burn injury was eliminated."

December 6, 2023

Sex Differences in ADHD Symptoms and Related Cognitive Deficits in Youths

Sex Differences in ADHD Symptoms and Related Cognitive Deficits in Youths

To what extent does sex matter in the expression of ADHD symptoms and associated cognitive deficits among youths with ADHD?

A recently published meta-analysis of 54 studies by a Canadian team of researchers at the University of Quebec at Montreal suggests it makes little to no difference. A meta-analysis of 26 studies with over 5,900 youths found no significant difference in inattention symptoms, and a meta-analysis of 24 studies with over 5,500 youths likewise found no difference in hyperactivity-impulsivity symptoms. Separating out hyperactivity and impulsivity made no difference.

Given these results, it's no surprise that a meta-analysis of 15 studies with over 3,500 youths again found no significant divergence between the sexes for total ADHD symptoms. Parents and teachers differed, however, in their ratings of symptoms. Whereas parents observed no differences, teachers reported boys had slightly more inattention and hyperactive-impulsive behaviors than girls. Turning to cognitive functions, a series of meta-analyses found no significant sex differences for interference control, working memory, and planning scores. But boys performed slightly worse on inhibition and motor response inhibition. While the raw data also showed boys slightly under-performing girls on cognitive flexibility, strong evidence of publication bias made this unreliable.

The team also compared youths with ADHD and youths without ADHD. Both for females and for males, those differences in ADHD symptoms were - as would be expected - extremely large, whether for total symptoms, inattention, or hyperactivity-impulsivity. All cognitive function scores were moderately better for normally developing boys compared with boys with ADHD, and for normally developing girls compared with girls with ADHD. Yet once again, when comparing these effect sizes between girls and boys, there were no significant differences for any of the symptom and cognitive function effects.

"In other words," the authors wrote, "boys and girls with ADHD presented significantly more primary symptoms and executive and attention deficits than did their peers without ADHD, and effect sizes were not significantly different between the sexes." They concluded, "girls with ADHD do not differ from boys with ADHD in many domains of cognitive functioning, and they have significantly more severe difficulties across the executive and attentional functions measured relative to girls without ADHD. This meta-analysis is the first to examine sex differences in cognitive flexibility, working memory, and planning."

December 11, 2023

Hypertensive Disorders of Pregnancy and Offspring ADHD: An Exploration

Two nationwide population studies explore relationship between maternal hypertensive disorders of pregnancy and ADHD in offspring

Two new studies, examining entire nationwide populations on opposite sides of the world, have just reported findings on the association between hypertensive disorders of pregnancy (HDP) and subsequent ADHD in off spring. HDP includes chronic hypertension, pre-eclampsia, pre-eclampsia superimposed on chronic hypertension, and gestational hypertension.

According to the Mayo Clinic, Preeclampsia is a pregnancy complication characterized by high blood pressure and signs of damage to another organ system, most often the liver and kidneys. Preeclampsia usually begins after 20 weeks of pregnancy in women whose blood pressure had been normal. Left untreated, it can lead to serious complications for both mother and baby and can be fatal. This range of conditions affects more than one in twenty pregnancies worldwide. HDP hampers permeability of the placenta, which may reduce delivery of blood-borne oxygen and nutrients to the fetus, potentially affecting brain development. ADHD could thus theoretically emerge as a neurodevelopmental outcome.

To what extent is this borne out in national-wide population studies? Both Taiwan and Sweden have single-payer national health insurance systems that systematically track virtually every resident. One study team used the Taiwan National Health Insurance research database to examine a cohort of 877,233 children born between 2004 and 2008. The other study team used the Swedish national registers to explore a cohort of 1,085,024 individuals born between 1987 and 1996.

The Taiwanese study adjusted for the following covariate/confounders: year of birth, fetal sex, paternal age, maternal age, family income, urbanization level, maternal diabetes diagnosis, preterm birth, small for gestational age, and parental psychiatric disorders. The Swedish study adjusted for the calendar year of birth, offspring sex, maternal age, parity, height, body mass index, smoking, presentational diabetes, parental educational level, occupation, and marital status. In the Taiwanese population, children of mothers with hypertensive disorders during pregnancy were about 20% more likely to develop ADHD than those of mothers without such disorders. There was no significant difference between chronic hypertension and pregnancy-induced hypertension/pre-eclampsia.

In the Swedish population, children of mothers with hypertensive disorders during pregnancy were about 10% more likely to develop ADHD than those of mothers without such disorders. But the Swedish study also went a step further. It is incredibly difficult to identify all significant confounding variables. But if you have a large enough study population, one can examine the effect of restricting the analysis to siblings within the same families. In that way, one can control in large measure for familial confounding “ shared environment and heredity. In the subsample of siblings “ 1,279 exposed to HDP versus 1,607 not exposed “ those exposed to outerwear were 9% more likely to develop ADHD, but this outcome was not statistically significant.

Noting the reduced statistical power of the subsample, the authors nonetheless concluded, the magnitude of these associations might be too weak(for ADHD in particular) to be considered an important risk factor at the level of the general population  Moreover, in a separate cohort of 285,901 Swedish men born between 1982 and 1992 who attended assessments for military conscription, mildly lower cognitive scores among those exposed to HDP in uteri vanished altogether (mean difference = 0) when limited to comparisons between full siblings (1,917 exposed versus 2,044 not exposed).

November 14, 2023

ADHD symptoms and suicidal ideation in college

ADHD symptoms and suicidal ideation in college

The mechanisms underlying the association between ADHD symptoms and suicidal ideation are poorly understood. A team of researchers from France and Montreal set out to explore this relationship with 2,331 French college students.

The students were participants in the internet-based student Health Research Enterprise project, a prospective population-based cohort study of students in higher education institutions in France. The i-Share study includes a longitudinal collection of data on childhood and family history, lifestyle, health information, and psychosocial examinations during the college years and beyond. 15,528 participants were included in the initial cohort, of which 2,331 completed all the questionnaires and did not have any missing data at the one-year follow-up. The mean age was 21, and four out of five were women. ADHD symptoms were assessed at the initiation of the study. Suicidal ideation was evaluated through a questionnaire completed a year later. Before that, three months after initiation, participants filled out a mental health survey that inquired about two potential mediators of suicidal ideation: depressive symptoms and self-esteem.

After adjusting for potential confounding factors (e.g., sex, childhood adversity, living conditions, and substance use) and taking into account the role of the mediators, the effect of ADHD symptoms on suicidal ideation (i.e., the direct effect) was no longer statistically significant, whereas pathways through depressive symptoms and self-esteem were both statistically significant. The pathway through depressive symptoms accounted for 25% of the total effect, while the pathway through self-esteem accounted for 64% of the total effect. Most of this indirect effect of self-esteem was in turn explained by the unique effect of self-esteem (not explained by depression), which accounted for 45% of the association, whereas a smaller part was explained by the effect of self-esteem through depression (accounting for 19% of the total effect). Ultimately, both mediators had the same effect (45% vs. 44%). Patterns were similar for males and females.

The authors caution that the study sample was not representative of the population of college students. It relied on volunteers, females were overrepresented, and the dropout ratio was very high. Participants in the final sample were more satisfied with their financial resources during their college years and during childhood, and less frequently consumed tobacco, than those in the initial cohort. The researchers recommend that ADHD patients be screened for self-esteem, and point out that other studies have indicated that exercise, Internet support groups, and interpersonal group therapy can build self-esteem in young people.

October 19, 2021

Comorbidities and Risk of Premature Death in Individuals With ADHD

How do psychiatric comorbidities affect risk of premature death among children and adults with ADHD?

Comorbidities contribute substantially to premature mortality risks in ADHD patients, but even those with ADHD alone are at a 40% greater risk.

The Nordic countries maintain detailed registers of their inhabitants. This enables researchers to examine patterns over entire nations. An international research team used the Swedish national registers for a prospective cohort study of 2,675,615 persons in the Medical Birth Register born in Sweden over 27 years from January 1, 1983, through December 31, 2009. Follow-up was completed in December 2013, with the oldest cohort member aged 31. The mean age at study entry was 6, and the mean at follow-up was 11.

Using personal identification numbers, researchers were able to cross-reference with the National Patient Register and the National Drug Register. From this, they determined that 86,670 members of the cohort (3.2 percent) had ADHD, based either on records of clinical diagnosis or of prescription of ADHD drugs. Psychiatric comorbidities were likewise identified in the National Patient Register.

These comorbidities were significantly more prevalent in the ADHD population than in the rest of the cohort. For example, whereas only 2.2% of the non-ADHD group was diagnosed with substance use disorder (SUD), 13.3% of the ADHD group also had SUD, a six-fold difference. For depression, it was a seven-fold difference; for schizophrenia a nine-fold difference.

The ADHD group had a significantly higher risk of premature death from all causes than the non-ADHD group, with an adjusted hazard ratio(HR) of 3.94 (95% CI 3.51-4.43). Unintentional injury (36%) and suicide (31%)were the leading causes of death in the ADHD group. Those with ADHD were more than eight times more likely to die by suicide than non-ADHD individuals and roughly four times more likely to die from unintentional injury.

The vast majority of the increased risk appears to be associated with comorbid psychiatric conditions. Those with ADHD but no diagnosed comorbidities had an adjusted HR of 1.41 (95% CI 1.01-1.97). With a single comorbidity, the HR more than doubled to 3.71 (95% CI 2.88-4.78). With four or more comorbidities, it rose to a staggering 25.22 (95% CI 19.6-32.46).

The comorbid condition with the greatest impact was SUD, which increased the risk eight-fold by comparison with those with only ADHD (HR= 8.01, 95% CI 6.16-10.41). Anxiety disorder, schizophrenia, and personality disorder increased the risk about fourfold. Bipolar disorder, depression, and eating disorders increased risk by roughly two and a half times.

The co-variate analysis helped tease out what portion of the risk was associated with ADHD alone versus comorbid conditions. Adjusting for the year of birth, sex, birth weight, maternal age at birth, parental educational level, and parental employment status, those with ADHD (including comorbid conditions)were 2.7 times more likely to prematurely die of natural causes than those without. Adjusting for comorbid psychiatric conditions completely eliminated the risk from ADHD alone (HR = 1.01, 95% CI.72-1.42).

Likewise, those with ADHD (including comorbid conditions)were six times as likely to die of unnatural causes. Adjusting for early-onset comorbid disorders (such as conduct disorders, autism spectrum disorder, and intellectual disability) only modestly reduced the HR to 5.3, but further adjusting for later-onset comorbid disorders(including substance use disorder, depressive disorder, bipolar disorder, anxiety disorder, schizophrenia, personality disorder, and eating disorders)reduced the HR to 1.57 (95% CI 1.35-1.83), and reduced it to insignificance in the case of suicide (HR = 1.13, 95% CI .88-1.45).

Summing up, the lion's share of the greater risk of premature death in persons with ADHD is attributable to psychiatric comorbidities. Nevertheless, those with ADHD alone still face a 40 percent greater risk than those without ADHD.

The study did not examine the effects of ADHD medication, which the authors state should be analyzed because of documented potential benefits on ADHD symptoms and comorbid disorders.

The authors concluded, Among adults, early-onset psychiatric comorbidity contributed substantially to the premature mortality risks due to natural causes. On the other hand, later-onset psychiatric comorbidity, especially SUD, explained a substantial part of the risk for unnatural deaths, including all the risk of suicide deaths and most of the deaths due to unintentional injuries. These results suggest that overall health conditions and risk of psychiatric comorbidity should be evaluated clinically to identify high-risk groups among individuals with ADHD.

September 8, 2021

Exploring The Long-term Effects of Treating ADHD with Methylphenidate

Are there adverse effects to long-term treatment of ADHD with methylphenidate?

Although this review highlights the need for further research, it also upholds previous studies which support Methylphenidate as a safe and effective ADHD medication.

Methylphenidate (MPH) is one of the most widely-prescribed medications for children. Given that ADHD frequently persists over a large part of an individual’s lifespan, any side effects of medication initiated during childhood may well be compounded over time. With funding from the European Union, a recently released review of the evidence looked for possible adverse neurological and psychiatric outcomes.

From the outset, the international team recognized a challenge: “ADHD severity may be an important potential confounder, as it may be associated with both the need for long-term MPH therapy and high levels of underlying neuropsychiatric comorbidity.” Their searches found a highly heterogeneous evidence base, which made meta-analysis inadvisable. For example, only 25 of 39 group studies reported the presence or absence of comorbid psychiatric conditions; even among those, only one excluded participants with comorbidities. Moreover in only 24 of 67 studies was the type of MPH used (immediate or extended-release) specified. The team, therefore, focused on laying out an “evidence map” to help determine priorities for further research.

The team found the following breakdown for specific types of adverse events:

·  Low mood/depression. All three non-comparative studies found MPH safe. Two large cohort studies, one with over 2,300 participants, and the other with 142,000, favored MPH over the non-stimulant atomoxetine. But many other studies, including a randomized controlled trial (RCT), had unclear results. Conclusion: “the evidence base regarding mood outcomes from long-term MPH treatment is relatively strong, includes two well-powered comparative studies, and tends to favor MPH.”

·  Anxiety. Here again, all three non-comparative studies found MPH safe. But only two of seven comparative studies favored MPH, with the other five having unclear results. Conclusion: “while the evidence about anxiety as an outcome of long-term MPH treatment tends to favor MPH, the evidence base is relatively weak.”

·   Irritability/emotional reactivity. A large cohort study with over 2,300 participants favored MPH over atomoxetine. Conclusion: “the evidence base  is limited, although it includes one well-powered study that found in favor of MPH over atomoxetine.”

·  Suicidal behavior/ideation. There were no non-comparative studies, but all five comparative studies favored MPH. That included three large cohort studies, with a combined total of over a hundred thousand participants, that favored MPH over atomoxetine. Conclusion: “the evidence base  is relatively strong, and tends to favor MPH.”

·  Bipolar disorder. A very large cohort study, with well over a quarter-million participants, favored MPH over atomoxetine. A much smaller cohort study comparing MPH with atomoxetine, with less than a tenth the number of participants, pointed toward caution. Conclusion: “the evidence base  is limited and unclear, although it includes two well-powered studies.”

·  Psychosis/psychotic-like symptoms. By far the largest study, with over 145,000 participants, compared MPH with no treatment and pointed toward caution. A cohort study with over 2,300 participants favored MPH over atomoxetine. Conclusion: “These findings indicate that more research is needed into the relationship between ADHD and psychosis, and into whether MPH moderates that risk, as well as research into individual risk factors for MPH-related psychosis in young people with ADHD.”

· Substance use disorders. A cohort study with over 20,000 participants favored MPH over anti-depressants, anti-psychotics, and no medication. Other studies looking at dosages and durations of treatment, age at treatment initiation, or comparing with no treatment or “alternative” treatment, all favored MPH except a single study with unclear results. Conclusion: “the evidence base … is relatively strong, includes one well-powered study that compared MPH with antipsychotic and antidepressant treatment, and tends to favor MPH.”

·Tics and other dyskinesias. Of four non-comparative studies, three favored MPH, the other, with the smallest sample size, urged caution. In studies comparing with dexamphetamine, pemoline, Adderall, or no active treatment, three had unclear results and two pointed towards caution. Conclusion: “more research is needed regarding the safety and management of long-term MPH in those with comorbidities or tic disorder.”

·  Seizures or EEG abnormalities. With one exception, the studies had small sample sizes. The largest, with over 2,300 participants, compared MPH with atomoxetine, with inconclusive results. Two small studies found MPH safe, one had unclear results, and two others pointed towards caution. Conclusion: “While the evidence is limited and unclear, the studies do not indicate evidence for seizures as an AE of MPH treatment in children with no prior history  more research is needed into the safety of long-term MPH in children and young people at risk of seizures.”

·  Sleep Disorders. All three non-comparative studies found MPH safe, but the largest cohort study, with over 2,300 participants, clearly favored atomoxetine. Conclusion: “more research is needed into the relationship between ADHD, sleep, and long-term MPH treatment.”

· Other notable psychiatric outcomes. Two non-comparative studies, with 118 and 289 participants, found MPH safe. A cohort study with over 700 participants compared with atomoxetine, with inconclusive results. Conclusion: “there is limited evidence regarding long-term MPH treatment and other neuropsychiatric outcomes, and that further research may be needed into the relationship between long-term MPH treatment and aggression/hostility.”

Although this landmark review points to several gaps in the evidence base, it mainly supports prior conclusions of the US Food and Drug Administration) and other regulatory agencies (based on short-term randomized controlled trials) that MPH is safe for the treatment of ADHD in children and adults. Given that MPH has been used for ADHD for over fifty years and that the FDA monitors the emergence of rare adverse events, patients, parents, and prescribers can feel confident that the medication is safe when used as prescribed.

September 6, 2021

Adult ADHD: Diagnoses Versus Undiagnosed

How do undiagnosed but symptomatic adults compare with those diagnosed with ADHD?

The study team began with a representative sample of 69,972U. S. adults aged 18 years or older who completed the 2012 and 2013 U.S. National Health and Wellness Survey. These adults were invited to complete the Validate Attitudes and Lifestyle Issues in Depression, ADHD, and Troubles with Eating(VALIDATE) study, which included 1) a customized questionnaire designed to collect data on sociodemographic and clinical characteristics and lifestyle, and2) several validated work productivity, daily functioning, self-esteem, and health-related quality of life (HRQoL) questionnaires. Of the 22,937 respondents, 444 had been previously diagnosed with ADHD, and 1,055 reported ADHD-like symptoms but had no previous clinical diagnosis.

There were no significant differences between the two groups in terms of age, education, income, health insurance, and most comorbid disorders. But those who had not been previously diagnosed were significantly more likely to be first-generation Americans (p<.001), nonwhite (p<.001), unemployed (p=.024), or suffer from depression, insomnia, or hypertension.

After matching the two groups for sociodemographic characteristics and comorbid conditions, covariate comparisons were made between 436 respondents diagnosed with ADHD and 867 previously undiagnosed respondents. Among respondents who were employed, diagnosed individuals registered a mean work productivity loss of 29% as opposed to 49% for the previously undiagnosed (p<.001). They also registered a 37% level of activity impairment versus a 53% level among the undiagnosed(p<.001). On the Sheehan Disability Scale, which ranges from 0 (no impairment) to 30 (highly impaired), the diagnosed group had a mean of 10, as opposed to a mean of 15 for the undiagnosed (p<.001). Diagnosed respondents also significantly outperformed undiagnosed ones on the Rosenberg Self-Esteem Scale (19 versus 15, on a scale of 0 to 30, p<.001), and on two quality-of-life scales (p<.001).

Applying a linear regression mixed model to the matched sets, the diagnosed still scored 16 points better than the undiagnosed on the WPA I: GH Productivity Loss scale (p<.001), 14 points better on the WPA I: GH Activity Impairment scale (p<.001), 4.5 points better on the Sheehan Disability Scale(p<.001), almost 4 points on the Rosenberg Self-Esteem Scale (p<.0001), with comparable gains on the two quality-of-life scales (p<.001 and p<.0001).

The authors concluded, This comparison revealed that individuals who had been diagnosed with ADHD were more likely to experience better functioning, HRQoL [health related quality-of-life], and self-esteem than those with symptomatic ADHD. This result appears to be robust, withstanding several levels of increasingly rigorous statistical adjustment. That points to substantial benefits from the treatment that follows a diagnosis of adult ADHD.

September 4, 2021

Meta-analysis Finds Association Between ADHD and Suicidal Behaviors

Meta-analysis finds association between ADHD and suicidal behaviors

A newly published meta-analysis of 57 studies encompassing almost a third of a million participants has uncovered a very strong association between ADHD and suicide, a strong association with suicidal ideation, and a small-to-medium association with suicide attempts.

The population examined included children, adolescents, and adults. Only persons formally diagnosed were considered to have ADHD. Studies that included self-injuries without suicidal intent were excluded. Most of the studies focused on European and American populations, with one in six from other locations, mostly Asian.

The most striking result was for actual suicides. The odds ratio (OR) for four datasets encompassing roughly one hundred forty thousand participants was 6.69 (95% CI 3.24 to 17.39, p <.0001). As a frame of reference, an OR of 1.5 is a small effect size, 2.5 is a medium one, and 4.3 is a large one. That means the effect size, in this case, is very large.

For suicidal ideation, 23 datasets with a combined total of just over 73,000 participants produced a medium-to-large OR of 3.5 (95% CI 2.94 to 4.25, p < .0001). In three datasets with more than nine thousand participants that adjusted for confounders, the adjusted OR was 4.5 (95% CI 1.72 to 11.63, p < .0001), indicating a large effect size.

For suicide attempts, 44 datasets encompassing over 228,000 participants produced an OR of 2.4 (95% CI1.64 to 3.43, p < .0001). In six datasets with over 65,000 participants that adjusted for confounders, the adjusted OR dropped to 2.1 (95% CI 1.27 to 3.47,p = .005).

There was no evidence of publication bias for studies on suicides or suicidal ideation, but significant evidence of bias for studies on suicide attempts (Eager's p = .03). This means that studies with positive findings were more likely to be published than negative studies.

There was, however, strong statistical evidence for differences between studies in the size of their ORS.  This indicates that the pooled OR cannot summarize results from all datasets, and more work is needed to clarify why the ORS differs among studies.

The authors appropriately caution that their meta-analysis is not informative on cause-effect relationships, but offer as a hypothesis that ADHD contributes to suicidal spectrum behaviors (SSBs) through Impulsivity, a core symptom of ADHD, along with impaired decision-making and risk-taking, that characterize several individuals with ADHD Additionally, a sizeable portion of individuals with ADHD present with deficits in executive functions. As executive functions are implicated in the regulation of impulse control and emotions, executive dysfunctions may contribute to SSBs.

Given the large to very large effect sizes for suicide and suicidal ideation, the authors advise: Awareness of this association should prompt practitioners to systematically screen for SSBs in patients with ADHD at the first assessment and at each follow-up, which in turn should contribute to decreasing the risk of SSB's. This is particularly noteworthy considering that questionnaires/scales commonly used to screen/assess ADHD symptoms generally do not include suicide-related items.

August 29, 2021

Exploring The Long-term Effects of Treating ADHD with Methylphenidate

Are there adverse effects to long-term treatment of ADHD with methylphenidate?

Methylphenidate (MPH) is one of the most widely-prescribed medications for children. Given that ADHD frequently persists over a large part of an individual's lifespan, any side effects of medication initiated during childhood may well be compounded over time. With funding from the European Union, a recently released review of the evidence looked for possible adverse neurological and psychiatric outcomes.

From the outset, the international team recognized a challenge: ADHD severity may be an important potential confounder, as it may be associated with both the need for long-term MPH therapy and high levels of underlying neuropsychiatric comorbidity. Their searches found a highly heterogeneous evidence base, which made meta-analysis inadvisable. For example, only 25 of 39 group studies reported the presence or absence of comorbid psychiatric conditions, and even among those, only one excluded participants with comorbidities. Moreover, in only 24 of 67 studies was the type of MPH used (immediate or extended-release) specified. The team, therefore, focused on laying out an evidence map to help determine priorities for further research.

The team found the following breakdown for specific types of adverse events:

·        Low mood/depression. All three non-comparative studies found MPH safe. Two large cohort studies, one with over 2,300 participants, and the other with 142,000, favored MPH over the non-stimulant atomoxetine. But many other studies, including a randomized controlled trial (RCT), had unclear results. Conclusion: the evidence base regarding mood outcomes from long-term MPH treatment is relatively strong, includes two well-powered comparative studies, and tends to favor MPH.

·        Anxiety. Here again, all three non-comparative studies found MPH safe. But only two of seven comparative studies favored MPH, with the other five having unclear results. Conclusion: while the evidence about anxiety as an outcome of long-term MPH treatment tends to favor MPH, the evidence base is relatively weak.

·        Irritability/emotional reactivity. A large cohort study with over 2,300 participants favored MPH over atomoxetine. Conclusion: the evidence base is limited, although it includes one well-powered study that found in favor of MPH over atomoxetine.

·        Suicidal behavior/ideation. There were no non-comparative studies, but all five comparative studies favored MPH. That included three large cohort studies, with a combined total of over a hundred thousand participants, that favored MPH over atomoxetine. Conclusion: the evidence base is relatively strong, and tends to favor MPH.

·        Bipolar disorder. A very large cohort study, with well over a quarter-million participants, favored MPH over atomoxetine. A much smaller cohort study comparing MPH with atomoxetine, with less than a tenth the number of participants, pointed toward caution. Conclusion: the evidence base is limited and unclear, although it includes two well-powered studies.

·        Psychosis/psychotic-like symptoms. By far the largest study, with over 145,000 participants, compared MPH with no treatment, and pointed toward caution. A cohort study with over 2,300 participants favored MPH over atomoxetine. Conclusion: These findings indicate that more research is needed into the relationship between ADHD and psychosis, and into whether MPH moderates that risk, as well as research into individual risk factors for MPH-related psychosis in young people with ADHD.

·        Substance use disorders. A cohort study with over 20,000 participants favored MPH over anti-depressants, anti-psychotics, and no medication. Other studies looking at dosages and durations of treatment, age at treatment initiation, or comparing with no treatment or alternative treatment, all favored MPH except a single study with unclear results. Conclusion: the evidence base is relatively strong, includes one well-powered study that compared MPH with antipsychotic and antidepressant treatment, and tends to favor MPH.

·        Tics and other dyskinetic. Of four non-comparative studies, three favored MPH, the other, with the smallest sample size, urged caution. In studies comparing with dexamphetamine, pemoline, Adderall, or no active treatment, three had unclear results and two pointed towards caution. Conclusion: more research is needed regarding the safety and management of long-term MPH in those with comorbidities or tic disorder.

·        Seizuresor EEG abnormalities. With one exception, the studies had small sample sizes. The largest, with over 2,300 participants, compared MPH with atomoxetine, with inconclusive results. Two small studies found MPH safe, one had unclear results, and two others pointed towards caution. Conclusion: While the evidence is limited and unclear, the studies do not indicate evidence for seizures as an AE of MPH treatment in children with no prior history more research is needed into the safety of long-term MPH in children and young people at risk of seizures.

·        Sleep Disorders. All three non-comparative studies found MPH safe, but the largest cohort study, with over 2,300 participants, clearly favored atomoxetine. Conclusion: more research is needed into the relationship between ADHD, sleep, and long-term MPH treatment.

·        Other notable psychiatric outcomes. Two noncomparative studies, with 118 and 289participants, found MPH safe. A cohort study with over 700 participants compared with atomoxetine, with inconclusive results. Conclusion: there is limited evidence regarding long-term MPH treatment and another neuropsychiatric outcome, and that further research may be needed into the relationship between long-term MPH treatment and aggression/hostility.

Although this landmark review points to several gaps sins in the evidence base, it mainly supports prior conclusions of the US Food antidrug Administration (FDA) and other regulatory agencies (based on short-term randomized controlled trials) that MPH is safe for the treatment of ADHD in children and adults.  Given that MPH has been used for ADHD for over fifty years and that the FDA monitors the emergence of rare adverse events, patients, parents, and prescribers can feel confident that the medication is safe when used as prescribed.

August 25, 2021

Outcomes of Mindfulness-Based Interventions on Adults with ADHD

Behavioral and Cognitive Impacts of Mindfulness-Based Interventions on Adults with ADHD

A Canadian team has published a systematic review examining the effectiveness of Mindfulness-Based Interventions (MBIs) for treating adults with ADHD. MBIs usually involve three forms of meditation “ body scan, sitting meditation, and mindful yoga “ that are intended to cultivate nonjudgmental awareness of the present-moment experience. The team reviewed thirteen studies.

Three were single-group studies with no control group. One used dialectical behavior therapy (DBT). It reported mild to moderate improvements in ADHD symptoms, and substantial improvements in neurocognitive function (with standardized mean difference effect sizes from .99 to 2.22). A second enrolled both adults and adolescents in a mindful awareness program (MAP)which included a psychoeducational component. It found improvements in itself-reported ADHD symptoms, with standardized mean difference (SMD) effect sizes running from .50 to.93. Following training, it also reported improvement in attentional conflict (.93) set-shifting (.43). The third study also used DBT, which focused on acceptance, mindfulness, functional behavioral analysis, and psychoeducation. ADHD symptoms showed mild improvement (.22), and functional impairment was slightly reduced (.15) and remained stable at the 3-month follow-up.

The other ten studies used control groups. One used MAP and carefully stratified participants based on their ADHD medication status, then randomly assigned them to mindfulness treatment or waitlist. It reported large effect sizes in the improvement of self-reported and clinician ratings of ADHD symptoms (1.35 to 3.14), executive functioning (1.45 to 2.67), and self-reported emotion regulation (1.27 to 1.63). Another study non randomly assigned adults to either mindfulness-based training (MBT) or skills training. Effect sizes were small to medium (.06 to .49), with 31% of MBT participants showing some improvement, versus only 11% of skills training participants.

Another study involved a controlled trial of college students with ADHD, randomized to receive either MBT or skills treatments. Treatment response rates were higher for MBT (59-65%, vs. 19-25%). In follow-up, the effect size for MBT on ADHD symptoms was large (.84), and similarly large on executive functioning (.81).

Another study tried a year's worth of mindfulness training for poor responders to medication. Participants who received the treatment were compared to others who were waitlisted. The study reported a medium effect size(.63) in reducing the severity of ADHD.

Another looked at the impact of MAP on affective problems and impaired attention. It compared adults with ADHD and healthy controls who participated in MAP sessions with similar patients and controls who did not. The authors reported that MAP improved sustained attention and mood, with medium to large effect sizes (.50 to .80).

A recent study explored the impact of MAP on neurocognitive performance with a randomized controlled trial. Following an 8-week mindfulness training, researchers found a significant decrease in ADHD symptoms and significant improvement in task performance in both the MAP and the psychoeducation comparison group post- versus pre-intervention but did not find evidence for a significant main effect of treatment or a significant interaction effect on any ADHD symptoms (self-and observer-rated) nor on task performance (WM).

Another study randomly assigned adults with ADHD either to the waitlist or mindfulness-based cognitive therapy (MBCT). It found that MBCT led to a medium-to-large reduction in self-reported ADHD symptoms (.64) and a large reduction in investigator-reported symptoms (.78). It also found large(.93) improvements in executive functioning.

An 11th study looked at the effects of MBCT on neuropsychological correlates (event-related potentials (ERPs)) of performance monitoring in adults with ADHD. Half the patients were randomly assigned tomb cut, and the other half to the waitlist. MBCT produced reduced inattention, hyperactivity/impulsivity, and global ADHD index symptoms with medium to large effect sizes (.49 to .93).

A 12th study randomly assigned college students to MBCT or waitlist. At follow-up, participants who had received MBCT exhibited large (1.26) reductions in ADHD symptoms as well as greater treatment response rates (57%-71% vs. 23%-31%) versus waitlist. They also registered a greater improvement in most neuropsychological performance and attentional scores.

Finally, another study compared the efficacy of MBCT plus treatment as usual (TAU) versus TAU only in reducing core symptoms in adults with ADHD. Participants were randomly assigned to an 8-weekly group therapy including meditation exercises, psycho-education, and group discussions, or TAU only, including pharmacotherapy and/or psychoeducation. At 6-month follow-up, MBCT+TAU patients reported large (SMD = .79) improvements in ADHD symptoms relative to patients.

Overall, these are promising results of mindfulness-based interventions, and all the more so for those who do not respond well to drug therapy. Nevertheless, they must be seen as tentative. The total of participants overall in thirteen studies was just 753, or an average of only 58 per study. There was too much variation in the studies to perform a meta-analysis. Only one of the studies included a healthy (non-ADHD) control group. And only one study received a perfect score from Cochrane Collaboration standards.  Most studies did not use a suitable control group, i.e., one in which there was an expectation of benefit from participating.  As the authors noted, "Attrition bias was found to have high or unclear risk in more than a half of the studies. The reason for dropout of participants was not always clearly specified in those studies, so it is difficult to decide if it might be related to adverse effects or some discomfort with treatment or instead to some incidental reasons."

August 23, 2021

Can ADHD be Treated With Mindfulness-Based Interventions?

How effective are mindfulness-based interventions in treating attention deficit symptoms?

Mindfulness has been defined as intentionally directing attention to present moment experiences with an attitude of curiosity and acceptance. Mindfulness-based interventions (MBIs) aim to improve mindfulness skills.

A newly-published meta-analysis of randomized controlled trials (RCTs) by a team of British neurologists and psychiatrists explores the effectiveness of MBIs in treating a variety of mental health conditions in children and adolescents. Among those conditions is the attention deficit component of ADHD.

A comprehensive literature search identified studies that met the following criteria:

1)     The effects of mindfulness were compared against control conditions “either no contact, waitlist, active, or attention placebo. The waitlist means the control group receives the same treatment after the study concludes. Active control means that a known, effective treatment (as opposed to a placebo) is compared to an experimental treatment. Attention placebo means that controls receive a treatment that mimics the time and attention received by the treatment group, but is believed not to have a specific effect on the subjects. Participants were randomly assigned to the control condition.
2)     The MBI was delivered in more than one session by a trained mindfulness teacher, involved sustained meditation practice, and was not mixed in with another activity such as yoga.

Eight studies evaluating attention deficit symptoms, with a combined total of 1,158 participants, met inclusion criteria. The standardized mean difference (SMD) was 0.19, with a 95% confidence range of 0.04 to 0.34 (p= .02). That indicates a small effect size for MBIs in reducing attention deficit symptoms. Heterogeneity was low (I2 = 35, p = .15), and teenager test showed little sign of publication bias (p = 0.42).

When looking only at studies with active controls, five studies with a total of 787 participants yielded an SMD of 0.13, with a 95%confidence interval of -0.01 to 0.28 (p = .06), indicating a tiny effect size that failed to reach significance. Active controls most commonly received health education, with a few receiving social responsibility training or Hath a yoga.

Overall, this meta-analysis suggests limited effectiveness, especially when compared with active controls.  If MBIs are effective for ADHD, their effect on symptoms is very small.  Thus, such treatments should not be used in place of the many well-validated, evidenced-based therapies available. Whether longer periods of MBI (training times varied between 2 and 18 hours spread out over 2to 24 weeks) might result in greater effect sizes remains unexplored.

August 21, 2021

Link Found Between ADHD Risk Genes and Reduced Estimated Life Expectancy

Association found between ADHD risk genes involved in dopamine signaling and reduced estimated life expectancy

Behavioral disinhibition is a trait associated with both ADHD and several genes that affect dopamine signaling. A new study by three American medical researchers set out to examine how these ADHD risk genes - DRD4 (dopamine 4 receptor density), DAT1 (dopamine 1 transporter), and DBH(dopamine beta-hydroxylase) - affect estimated life expectancy in young adulthood.

The method used was a longitudinal study of 131 hyperactive children and 71 matched controls through early adulthood. The original evaluations were done in 1979-1980, when both groups were children in the 4 to 12 age range. They were reevaluated in1987-1988 as adolescents aged 12 to 20. The next follow-up was in 1992-1996 in early adulthood, aged 19 to 25. The final follow-up was in 1998-2004, for adults aged 24 to 32. All agreed to physical examinations that formed the basis for calculating estimated life expectancy using actuarial tables that factor in the effects of smoking, body mass index, alcohol, and other risk factors of on expected longevity. Participants also provided blood samples that enabled gene typing.

For the DAT1 gene, participants who had the homozygous-repeat allele (9/9) had a five-year reduction in estimated life expectancy relative to those with the ten-repeat allele (10/10). Those with the intermediate (9/10) configuration had a three-year reduction in estimated life expectancy.

For the DBH Taq1 gene, those with a heterozygous (A1/A2) combination had almost a three-year reduction in estimated life expectancy relative to those with homozygous (A1/A1 or A2/A2)configurations.

For DRD4, on the other hand, no significant differences were found in estimated life expectancy.

In a related study, several background traits were found to be significantly predictive of variance estimated life expectancy. The largest of these was behavioral disinhibition, followed by verbal IQ, self-rated hostility, and a nonverbal fluency test. But no significant differences were found between any of the gene polymorphisms on any of these four measures, indicating that the present gene associations were independent of the background traits.

The researchers next sought to determine which variables used in the estimated life expectancy calculations were associated with the two significant genes. For DBH, one variable stood out. Those with the A1/A2 heterozygous pairings had almost twice the alcohol consumption of those with homozygous pairings (p = 0.023).

For DAT1, two variables stood out. Overall, the 9/9 pairings smoked two and a half times as much as the 10/10pairings, with the 9/10 pairings midway between the extremes (p = 0.036). They were also 73 percent more likely to be smokers relative to the 10/10 pairings, and 61 percent more likely relative to the 9/10 pairings. They also had significantly less education than the 10/10 pairings, with the 9/10 pairings again being intermediate (p = 0.027).

An obvious limitation of the study was its small sample size. The authors cautioned, our findings should be considered quite preliminary and in need of much greater research before being given much weight in the literature or public policy.

"With these limitations in mind, they concluded, the present study demonstrated that two ADHD risk genes (DB Hand DAT1) independently contributed to a reduction in ELE [estimated life expectancy] beyond the second-order variables of behavioral disinhibition, IQ, hostility, and nonverbal fluency that contributed in the related study to variation in ELE. The gene polymorphisms seemed to be influencing ELE through their affiliation with first-order or more proximal factors related to ELE such as education, smoking, alcohol use, and possibly exercise."

August 19, 2021

Driving, Safety, and ADHD

How to Improve Driving Safety for Teens and Adults With ADHD

Drivers with ADHD are far more likely to be involved in crashes, to be at fault in crashes, to be in severe crashes, and to be killed in crashes. The more severe the ADHD symptoms, the higher the risk. Moreover, ADHD is often accompanied by comorbid conditions such as oppositional-defiant disorder, depression, and anxiety that further increase the risk.

What can be done to reduce this risk? A group of experts has offered the following consensus recommendations:

·        Use stimulant medications. While there is no reliable evidence on whether-stimulant medications are of any benefit for driving, there is solid evidence that stimulant medications are effective in reducing risk. But there is also a “rebound effect” in many individuals after the medication wears off, in which performance becomes worse than it had been before medication. It is therefore important to time the taking of medication so that its period of effectiveness corresponds with driving times. If one has to drive right after waking up, it makes sense to take a rapid-acting form. The same holds for late-night driving that may require a quick boost.
·        Use a stick shift vehicle wherever possible. Stick shifts make drivers pay closer attention than automatic transmissions. The benefits of alertness are most notable in city traffic. But using a stick shift is far less beneficial in highway driving, where shifting is less frequent.
·        Avoid cruise control. Highways can be monotonous, making drivers more prone to boredom and distraction. That is even more true for those with ADHD, so it is best to keep cruise control turned off.
·        Avoid alcohol. Drinking and driving is a bad idea for everyone, but, once again, it’s even worse for those with ADHD. Parents should consider the no-questions-asked policy of either picking up their teenager anytime and anywhere or setting up an account with a ride-sharing service.
·        Place the smartphone out of reach and hearing. Cell phone use is as about as likely to impair as alcohol. Hands-free devices only reduce this risk moderately, because they continue to distract. Texting can be deadly. Sending a short text or emoticon can be the equivalent of driving 100 yards with one’s eyes closed. Either turn on Do Not Disturb mode or, for even greater effectiveness, place the smartphone in the trunk.
·        Make use of automotive performance monitors. These can keep track of maximum speeds and sudden acceleration and braking, to verify that a teenager is not engaging in risky behaviors.
·        Take advantage of “graduated driver’s licensing laws” wherever available. These laws forbid the presence of peers in the vehicle for the first several (for example, six) months of driving. Parents can extend that period for teenagers with ADHD, or set it as a condition in states that lack such laws.
·        Encourage practicing after obtaining a learner’s permit. Teenagers with ADHD generally require more practice than those without. A “pre-drive checklist” can be a good place to start. For example: check the gas, check the mirrors, make sure the view through the windows is unobstructed, put your cell phone in Do not disturb mode and place it out of reach, put on a seatbelt, and scan for obstacles.
·        Consider outsourcing. Look for a driving school with a professional to teach good driving skills and habits.

Experts do not agree on whether to delay licensing for those with ADHD. On the one hand, teenagers with ADHD are 3-4 years behind in the development of brain areas responsible for executive functions that help control impulses and better guide behavior. Delaying licensing can reduce risk by about 20 percent. On the other hand, teens with ADHD are more likely to drive without a license, and no one wants to encourage that, however inadvertently. Moreover, graduated driver’s licensing laws only have a legal effect on teens who get their licenses at the customary age.

August 13, 2021

How to Identify ADHD in Adults With Alcohol Use Disorder (AUD)

How to identify ADHD in adults with alcohol use disorder (AUD)

ADHD is far more prevalent among persons with AUD (roughly20 percent) than it is in the general population. The most accurate way of identifying ADHD is through structured clinical interviews. Given that this is not feasible in routine clinical settings, ADHD self-report scales offer a less reliable but much less resource-intensive alternative. Could the latter be calibrated in a way that would yield diagnoses that better correspond with the former?

A German team compared the outcomes of both methods on 404 adults undergoing residential treatment for AUD. All were abstinent while undergoing evaluations. First, to obtain reliable ADHD diagnoses, each underwent the Diagnostic Interview for ADHD in Adults, DIVA. If DIVA indicated probable ADHD, two expert clinicians conducted successive follow-up interviews. ADHD was only diagnosed when both experts concurred with the DIVA outcome.

Participants were then asked to use two adult ADHD self-report scales, the six-item Adult ADHD Self Report Scale v1.1 (ASRS) and the 30-item Conner's Adult ADHD Rating Scale (CAARS-S-SR). The outcomes were then compared with the expert interview diagnoses.

Using established cut-off values for the ASRS, less than two-thirds of patients known to have ADHD were scored as having ADHD by the test. In other words, there was a very high rate of false negatives. Lowering the cut-off to a sum score ≥ 11 resulted in an incorrect diagnosis of more than seven out of eight. But the rate of false positives shared to almost two in five. Similarly, the CAARS-S-SR had its greatest sensitivity (ability to accurately identify those with ADHD) at the lowest threshold of ≥ 60, but at a similarly high cost in false positives (more than a third).

The authors found it was impossible to come anywhere near the precision of the expert clinical interviews. Nevertheless, they judged the best compromise to be to use the lowest thresholds on both tests and then require positive determinations from both. That led to successfully diagnosing more than three out of four individuals known to have ADHD, with a false positive rate of just over one in five.

Using this combination of the two self-reporting questionnaires with lower thresholds, they suggest, could substantially reduce the under-diagnosis of ADHD in alcohol-dependent patients.

August 5, 2021

Pharmacotherapy and ADHD in Adults with Autism Spectrum Disorder

How effective is pharmacotherapy of ADHD in adults with Autism Spectrum Disorder?

Autism spectrum disorder (ASD) is frequently comorbid with ADHD. Among adults with ADHD, as many as half are reported to also have ASD.

A Dutch team set out to answer two questions:

1)    Do adults with ADHD and comorbid ASD experience less effectiveness in pharmacological treatment for ADHD than adults with only ADHD
2)    Do adults with ADHD and comorbid ASD experience different or more severe side effects of pharmacological treatment for ADHD than adults with only ADHD, as measured in side effect scores, blood pressure, heart rate, and weight?

This was a retrospective study, using well-documented medical records, of the effects of drug treatment with methylphenidate (MPH), dexamphetamine (DEX), atomoxetine (ATX), bupropion, or modafinil.

The researchers compared 60 adults with comorbid ASD and ADHD to 226 adults with only ADHD. ADHD symptoms were scored using the Conner's ADHD Rating Scale: Self Report-Short Version (CAA RS: S-S). Side effects of ADHD medication were measured using either a 13-item or 20-item checklist with 4-point scales for item response. Researchers also tracked changes in body weight, blood pressure, and heart rate.

Following treatment, ADHD symptoms among the comorbid group declined by a quarter, and among the ADHD-only group by almost a third. There was no significant difference between men and women. Controlling for age, gender, and ADHD subtype, a comorbid diagnosis of ASD also did not significantly affect ADHD symptom reduction.

Turning to side effects, in the ADHD+ASD group, there were significant increases in decreased appetite and weight loss, and decreases in agitation, anxiety, and sadness/unhappiness. In the ADHD-only group, there were significant increases in decreased appetite, weight loss, and dry mouth, and decreases in sleeping disorder, nervousness, agitation, anxiety, and sadness/unhappiness. Yet there were no significant differences between the two groups. Side effects increased and decreased similarly in both. Likewise, there were no significant differences between the groups in changes in heart rate and blood pressure. The only significant difference in medication dosage was for bupropion, which was higher in the ADHD+ASD group, though without any sign of the difference in side effects.

The authors concluded that this retrospective study "showed pharmacological treatment of adults with diagnoses of ADHD and ASD to be just as successful as the pharmacological treatment of adults with only ADHD," but cautioned that "randomized controlled trial should be conducted to evaluate the effectiveness and possible side effects of pharmacological treatment for ADHD in patients with ASD more reliably."

August 3, 2021

New Insights Into The Brains of People Living with ADHD and ADHD Symptoms

New insights into the brains of people living with ADHD and those with ADHD symptoms.

In this study, researchers found subtle differences in the cortex of the brains of children with ADHD.

The ENIGMA-ADHD Working Group published a second large study on the brains of people with ADHD in the American Journal of Psychiatry this month. In this second study, the focus was on the cerebral cortex, which is the outer layer of the brain.

 ADHD symptoms include inattention and/or hyperactivity and acting impulsively. The disorder affects more than one in twenty (5.3%) children, and two-thirds of those diagnosed continue to experience symptoms as adults.
In this study, researchers found subtle differences in the brain's cortex when they combined brain imaging data on almost 4,000 participants from 37 research groups worldwide. The differences were only significant for children and did not hold for adolescents or adults. The childhood effects were most prominent and widespread for the surface area of the cortex. More focal changes were found in the thickness of the cortex. All differences were subtle and detected only at a group level, and thus these brain images cannot be used to diagnose ADHD or guide its treatment.

These subtle differences in the brain's cortex were not limited to people with the clinical diagnosis of ADHD: they were also present - in a less marked form - in youth with some ADHD symptoms. This second finding results from a collaboration between the ENIGMA-ADHD Working Group and the Generation Study from Rotterdam, which has brain images of, 2700 children aged 9-11 years from the general population. The researchers found more symptoms of inattention to be associated with a decrease in cortical surface area. Furthermore, siblings of those with ADHD showed changes to their cortical surface area that resembled their affected sibling. This suggests that familial factors such as genetics or shared environment may play a role in brain cortical characteristics.

This is the largest study to date to look at the cortex of people with ADHD. It included 2246 people with a diagnosis of ADHD and 1713 people without, aged between 4 and 63 years old. This is the second study published by the ENIGMA-ADHD Working Group; the first examined structures that are deep in the brain. The ADHD Working Group is one of over 50 working groups of the ENIGMA Consortium, in which international researchers pull together to understand the brain alterations associated with different disorders and the role of genetic and environmental factors in those alterations.

The authors say the findings could help improve understanding of the disorder. 'We identify cortical differences that are consistently associated with ADHD, by combining data from many research groups internationally. We find that the differences extend beyond narrowly-defined clinical diagnoses and are seen, in a less marked manner, in those with some ADHD symptoms and unaffected siblings of people with ADHD. This finding supports the idea that the symptoms underlying ADHD may be a continuous trait in the population, which has already been reported by other behavioral and genetic studies.'. In the future, the ADHD Working Group hopes to look at additional key features in the brain - such as the structural connections between brain areas - and to increase the representation of adults affected by ADHD, on whom limited research has been performed to date.

August 1, 2021

Social and Self-Stigmatization in Adults with ADHD

Social and Self-Stigmatization in Adults with ADHD

A German team recruited 104 adults with ADHD at both inpatient and outpatient ADHD clinics, and from ADHD self-help groups. Just under two-thirds were being treated with ADHD drugs, most with methylphenidate.

Just under a quarter reported high internalized stigma. Two in five reported high levels of alienation, meaning a sense of "not being a fully functioning, valuable member of society." Three in ten reported high levels of social withdrawal.

On the other hand, only two participants reported high levels of stereotype endorsement, meaning personal acceptance of stereotypes associated with mental illness. And more than two-thirds reported high stigma resistance, meaning they were internally resistant to stigmatization. Thus, while most were free of significant internalized stigma, a still substantial minority were not.

Most of the participants expected to be discriminated against and treated unfairly by employers, colleagues at work, neighbors, and teachers should they reveal that they have ADHD. Relatively few expected to be discriminated against by health professionals, family, and friends. Almost half expected discrimination if they confided to strangers they were dating.

Over two-thirds of participants reported they had encountered public stereotypes concerning ADHD. But, on balance, they rated these at low levels of intensity. Nevertheless, among those perceiving such stereotypes, eight out of nine sensed some degree of public doubt about the validity of ADHD as a genuine ailment ("ADHD does not exist in adults"), and three out of four had at some point encountered the argument that "ADHD is invented by drug companies." More than four out of five had heard allegations that ADHD results from bad parenting, and almost three in four had heard the claim that it results from watching too much television or playing too many video games.

These data call for more education of the public about the nature and causes of ADHD. Information reduces stigmatization, so the widespread dissemination of the facts about ADHD is warranted.

April 8, 2024

Are Shared Care Models Effective in Treating Childhood ADHD?

Are Shared Care Models Effective in Treating Childhood ADHD?

A systematic review found five studies that evaluated shared care models involving children and adolescents, in which primary care providers(PCPs) collaborated with mental health care providers in treating ADHD. The 655 participants ranged in age from 5 to 17. Two of the studies were randomized.

In one, the largest, with 321 participants, care managers acted as liaisons between PCPs and psychiatrists and provided psychoeducation and skills training for families. Effect sizes on the Vanderbilt ADHD Diagnostic Teacher Rating Scale were very small, ranging from a standardized mean difference (SMDs) of 0.07 to 0.12. Improvement on the Clinical Global Impression scale was also small (SMD = 0.3)and was not significant (p = 0.4).

In the other randomized study, with 63 participants, care managers also acted as liaisons between PCPs and a psychiatric decision support panel to provide Positive Parenting Training. The SNAP-IV hyperactivity/impulsivity score showed a medium effect size (SMD = 0.7), with a medium-to-large effect size (0.7) for improvement in social skills. The score difference for SNAP-IV inattention was not statistically significant. The other three studies followed groups of individuals over time.

In one cohort with 129 participants, PSPs consulted with psychiatrists by telephone; an evaluation, where necessary, was performed within 4 weeks. As assessed by the Clinical Global Impression-Severity scale, symptoms declined from moderately severe to mild or borderline. On the Children's Global Assessment Scale, there was an improvement from problems in more than one area of functioning to just one area.

In another cohort with 116 participants, care managers acted as liaisons between pediatricians and a psychiatrist and provided education to parents. Just over a quarter of participants showed improvement of greater than one standard deviation on the Vanderbilt ADHD Diagnostic Parent Rating Scale, and just under one in seven on the Vanderbilt ADHD Diagnostic Teacher Rating Scale.

The remaining cohort had only 26 participants. It offered PCPs access to outpatient psychiatric consultations within three weeks. PCPs reported a high level of satisfaction with their improved skills in mental health care. There was no evaluation of the effect on symptoms.

With varied study designs, methodologies, and outcomes, the authors of the review could only conclude "that PCP collaboration with psychiatrists may be associated with the increased comfort level. However, the association with symptom outcome and increased capacity was variable." Given that randomized studies report only small effects, these shared care models cannot be routinely recommended.

July 22, 2021

Is There a Relationship Between ADHD and Migraines?

Is there a relationship between ADHD and migraines?

A Danish team recruited 29,489 participants from voluntary blood donors between the ages of 17 and 67, ensuring a large sample size. Participants were asked to complete two simple questionnaires on digital tablets. One asked two questions: "Have you ever had a migraine?" and "Have you ever had visual disturbances lasting 5-60 min followed by a headache?" A yes to either was considered positive for migraine. The other used the ADHD Self-Report Scale, with 18 ADHD symptoms evaluated on a five-point scale.

Excluding those who did not answer all questions left 26,456 participants. The risk for migraines among those with ADHD was near twice the risk for others. The (odds)'s ratio (OR) was 1.8, with a 95 percent confidence interval from 1.53 to 2.12 (p < 0.001). The OR was higher among females (2.01) than males (1.64). For those with visual disturbances, the OR was higher (1.98) than for those without (1.52). The association disappeared in those over 60, with an OR essentially equal to one(0.98, 95% CI = 0.84 - 1.15, p = 0.8).

Although the authors concluded, "We demonstrate a significant comorbidity between migraine and ADHD in adults, and this is most prominent for participants with migraine with visual disturbances," the significance to which they refer is of the p-values, and should not be misinterpreted as an indication of a strong association, as the odds ratios point variably tweak, and weak-to-moderate associations, depending on subpopulations.  The work is, however, important as it points to another somatic comorbidity of ADHD. That list is growing and now includes obesity, eczema, and asthma.

July 14, 2021

How Effective are Meditation-based Therapies for ADHD?

How effective are meditation-based therapies for ADHD?

An international team of researchers recently published a meta-analysis of randomized controlled trials examining the efficacy of meditation-based therapies. Thirteen randomized controlled clinical trials(RCTs) were included: seven, with 270 participants, focused on children and adolescents; the other six, with 339 participants, were on adults. Because only one of the RCTs was appropriately blinded, the results discussed below, although promising, must be considered preliminary.

Among children and adolescents, the meta-analysis revealed a significant, medium effect size (SMD = -0.44, 95% CI -0.69 to -0.19)on ADHD symptoms for meditation therapy versus no treatment. There were virtually no heterogeneity among studies and no sign of publication bias. Improvements in inattention and hyperactivity/impulsivity had similar effect sizes. Neuropsychological measures of inhibition and attention indicated small-to-medium effect sizes but failed to achieve statistical significance, perhaps due to the small numbers of trials and participants (159 and 179, respectively).

For adults, the significant effect size on ADHD symptoms was medium-to-large (SMD = -.66, 95% CI -1.21 to -0.11). Once again, there was little sign of publication bias. But in this case, there was great heterogeneity among the studies. Improvements in inattention and hyperactivity/impulsivity were again comparable, although they fell just short of statistical significance for the latter. Neuropsychological measures of the efficacy of medication therapy produced statistically significant medium effect sizes for inhibition (SMD = -0.54) and working memory (SMD = - 0.42), with virtually no heterogeneity or sign of publication bias.

Although these results are promising, the authors of the meta-analysis concluded, "Despite statistically significant effects on ADHD combined core symptoms, due to paucity of RCTs, heterogeneity across studies, and lack of studies at low risk of bias, there is insufficient methodologically sound evidence to support meditation-based therapies for ADHD."

July 12, 2021

Is prenatal antidepressant exposure a risk factor for ADHD?

Is prenatal antidepressant exposure a risk factor for ADHD?

A systematic review of the literature found seven studies examining this question. Significantly, six were large cohort studies with a combined total of almost three million individuals. The other was a large case-control study with 7,874 participants.
The largest cohort study, with more than a million and a half children, found that prenatal antidepressant exposure increased the risk for ADHD.  The adjusted odds ratio was 1.6forany antidepressant and for selective serotonin reuptake inhibitors (SSRI). But sibling comparison models, which better adjust for confounds shared by siblings(e.g., poverty, stress in the home), this study found no increased risk of ADHD.
The second-largest cohort study, with over 875 thousand children, found a small adjusted risk of 1.2 for all antidepressants, with little variation by class of antidepressant. The fourth-largest study, with over 140 thousand children, likewise found a small adjusted risk of 1.2, which barely achieved statistical significance (95% CI 1.0-1.4).
The third-largest study, with over 190 thousand children, obtained an adjusted risk of 1.4 for all antidepressants. But it also pointed to a possible explanation for the small association found in this and other studies, suggesting that the apparent association with antidepressant use was due to ADHD's known genetic association with psychiatric conditions treated by antidepressants.
The fifth-largest study, with more than 55 thousand children, similarly found an adjusted risk of 1.7 for SSRIs and an adjusted risk of 1.7 for an unmediated maternal psychiatric disorder. Again, the underlying psychiatric disorder appears to be confounding the effect of antidepressants.
The sixth-largest study, with over 38 thousand children, found no evidence of any effect from SSRIs. Yet it found evidence of a large effect from bupropion, with an odds ratio of 3.6, and only one in 50 odds of obtaining such a result by chance (p = 0.02). However, it offered no comparison with untreated depression and made no adjustments for potential confounders.
The case-control study found an odds ratio of 2.3 for maternal use of any antidepressant, which dropped to a statistically non-significant 1.6 when adjusted for a maternal psychiatric disorder (95% CI0.66-3.71).

July 10, 2021

High Dropout Rate in Six-Year Cohort Study of Medication Treatment for ADHD

High Dropout Rate in Six-Year Cohort Study of Medication Treatment for ADHD

Few studies have examined the safety and tolerability of ADHD medications (stimulants and atomoxetine) extending beyond six months, and none beyond a few years. A pair of Swedish neuroscientists at Uppsala University Hospital set out to explore longer-term outcomes. They conducted a six-year prospective study of 112 adults diagnosed with ADHD who were being treated with ADHD medications (primarily MPH, but also dexamphetamine and atomoxetine).

They found that at the end of that period, roughly half were still on medication, and half had discontinued treatment. There were no significant differences between the two groups in age, sex, ADHD severity, or comorbidity. The average ADHD score for the entire cohort declined to vary significantly, from a mean of 37 to a mean of 26, with less than one in a thousand odds of that being due to chance. There was also no sign of drug tolerance or a need to increase the dosage over time.
All 55 adults who discontinued treatment had taken MPH for at least part of the time. Eleven had also been treated with dexamphetamine(DEX) and 15 with atomoxetine (ATX). The average time on treatment was just under two years. Almost a third quit MPH because they perceived no beneficial effect. Since they were on average taking higher doses at discontinuation than initiation, that is unlikely to have been due to suboptimal dosage. Almost another third was discontinued for various adverse mental effects, including hyperactivity, elation, depressive moods, aggression, insomnia, fatigue, and lethargy. Another one in eleven quit when they lost contact with the prescribing physician. In the case of ATX, almost half quit because of what they perceived as adverse mental effects.

Among the 57 adults who remained on medication, four out of five reported a strong beneficial effect. Only two reported minimal or no effect. Compared with the group that discontinued, the group that remained on medication was far more likely to agree with the statements, "My quality of life has improved," and "My level of functioning has improved." Yet, as the authors caution, it is possible "that the subjects' subjective ratings contained a placebo-related mechanism in those who are compliant with the medication and pursue treatment over time." The authors reported that there were no significant differences in ADHD scores or ADHD severity between the group that quit and the group that remained on medication, even though, on average, the group that quit had been off medication for four years at follow-up.

We cannot explain why the patients who quit treatment showed similar levels of ADHD symptoms to those who continued treatment.  It is possible that some patients remit symptoms over time and do not require sustained treatment.  But we must keep in mind that there was a wide range of outcomes in both groups. Future work needs to find predictors of those who will do well after treatment withdrawal and those who do not.

Any decision on whether to maintain a course of medication should always weigh expected gains against adverse side effects. Short of hard evidence of continuing efficacy beyond two years, adverse events gain in relative importance. With that in mind, it is worth noting that this study reports that among those who remained on MPH, many reported side effects. More than a quarter complained of decreased appetite, one in four of dry mouth, one in five of anxiousness and increased heart rate, one in six of decreased sexual desire, one in nine of depressed mood, and one in eleven of insomnia.

This study breaks important ground in looking at the long-term effects of medication. It reaffirms findings elsewhere of the efficacy of ADHD medications. But contrary to the authors' conclusion, the data they present suggests the possibility that permanently medicating ADHD patients may not be more efficacious than discontinuation beyond a certain point, especially when balanced against adverse side effects.
But this is just one study with a relatively small sample size. This suggests a need for additional studies with larger sample sizes to pursue these questions with greater statistical reliability.

July 8, 2021

Researchers Have Found the First Risk Genes for ADHD

Researchers have found the first risk genes for ADHD

Our genes are very important for the development of mental disorders-including ADHD, where genetic factors capture up to 75% of the risk. Until now, the search for these genes had yet to deliver clear results.   In the 1990s, many of us were searching for genes that increased the risk for ADHD because we know from twin studies that ADHD had a robust genetic component.  Because I realized that solving this problem required many DNA samples from people with and without ADHD, I created the ADHD Molecular Genetics Network, funded by the US NIMH.  We later joined forces with the Psychiatric Genomics Consortium (PTC) and the Danish psych group, which had access to many samples.  
The result is a study of over 20,000 people with ADHD and 35,000 who do not suffer from it - finding twelve locations (loci) where people with a particular genetic variant have an increased risk of ADHD compared to those who do not have the variant.  The results of the study have just been published in the scientific journal Nature Genetics,
These genetic discoveries provide new insights into the biology behind developing ADHD. For example, some genes have significance for how brain cells communicate with each other, while others are important for cognitive functions such as language and learning.
Our study used the genome-wide association study (GWAS)methodology because it allowed us to discover genetic loci anywhere on the genome.  The method assays DNA variants throughout the genome and determines which variants are more common among ADHDvs. control participants.  It also allowed for the discovery of loci having very small effects.  That feature was essential because prior work suggested that, except for very rare cases, ADHD risk loci would individually have small effects.
The main findings are:

A) we found 12 loci on the genome that we can be certain harbor DNA risk variants for ADHD.  None of these loci were traditional candidate genes' for ADHD, i.e., genes involved in regulating neurotransmission systems that are affected by ADHD medications.  Instead, these genes seem to be involved in the development of brain circuits.  
B) we found a significant polygenic etiology in our data, which means that there must be many loci(perhaps thousands) having variants that increase the risk for ADHD.  We will need to collect a much larger sample to find out which specific loci are involved;

We also compared the new results with those from a genetic study of continuous measures of ADHD symptoms in the general population. We found that the same genetic variants that give rise to an ADHD diagnosis also affect inattention and impulsivity in the general population.  This supports prior clinical research suggesting that, like hypertension and hypercholesteremia, ADHD is a continuous trait in the population.  These genetic data now show that the genetic susceptibility to ADHD is also a quantitative trait comprised of many, perhaps thousands, of DNA variants
The study also examined the genetic overlap with other disorders and traits in analyses that ask the questions: Do genetic risk variants for ADHD increase or decrease the likelihood a person will express other traits and disorders.   These analyses found a strong negative genetic correlation between ADHD and education. This tells us that many of the genetic variants which increase the risk for ADHD also make it more likely that a person will perform poorly in educational settings. The study also found a positive correlation between ADHD and obesity, increased BMI, and type-2 diabetes, which is to say that variants that increase the risk of ADHD also increase the risk of overweight and type-2 diabetes in the population. This work has laid the foundation for future work that will clarify how genetic risks combine with environmental risks to cause ADHD.  When the pieces of that puzzle come together, researchers will be able to improve the diagnosis and treatment of ADHD.

July 4, 2021

Bad eating habits in adults with ADHD

Bad eating habits in adults with ADHD

An Israeli team compared eating habits and body mass index(BMI) in adults with and without ADHD. They recruited 60 students from Hebrew University in Jerusalem between 20 and 30 years old. To avoid bias due to particular diets, the authors excluded vegetarians and vegans, as well as persons with chronic diseases that require altered diets, such as diabetes, inflammatory bowel diseases, and chronic kidney disease. Twenty-nine of the participants had been diagnosed with ADHD.
All participants filled out the Food Frequency Questionnaire, a semi-quantitative scale querying about 119 food items. Based on World Health Organization guidelines, it distinguished between "healthy" items (such as vegetables, fruits, whole grains, and minimally processed foods)and "unhealthy" ones (such as cookies, processed meats, and other processed foods). The data obtained from the questionnaires were linked to a nutrient database to estimate daily nutrient intake. BMI was calculated from heights and weights reported by the students.
No significant differences were found between the two groups for servings, calories, fats, carbohydrates, and proteins. Yet, the ratio of healthy to unhealthy portions was significantly higher among controls than among those with ADHD. Those without ADHD consumed about a quarter more servings of healthy food and about a quarter fewer servings of unhealthy food.
On average, BMI levels were about 13 percent higher in participants with ADHD than among those without, meaning they were significantly more likely to be overweight. This finding is consistent with many prior studies.
The authors concluded, "Although participants in both groups consumed similar amounts of servings, calories, and nutrients, students with ADHD reported eating lower amounts of healthy food and higher amounts of unhealthy food. The results suggest that ADHD is not associated with general overeating, but with a biased proportion of unhealthy versus healthy food consumption."
They also recognized limitations to their study. One was a relatively small sample size and the fact that all participants were recruited from a single university. Another is that they did not try to fully evaluate the effects of medication, other than to note the absence of significant differences in food choices between those who used medication regularly and those who used it only occasionally. An unrecognized limitation was the exclusive reliance on self-reporting, both for food consumption, weight, and height.
Despite these limitations, this study is an important first step toward understanding the eating habits of people with ADHD.  It suggests to me that those treating ADHD should promote healthy lifestyles, as that should reduce ADHD's known risks of obesity and adverse medical outcomes.

July 2, 2021

CDC: Prescriptions for ADHD Medications in Reproductive Age Women on Rise

CDC Reports increase in prescriptions for ADHD Medications in Reproductive Age Women

The CDC recently reported that ADHD medication use in women ages 15 to 44 increased from 0.9 percent to 4 percent from 2003 to 2015.  The most commonly used medications were formulations of amphetamine or methylphenidate.  

This increase in treatment for ADHD suggests that educational programs such as have been effective in teaching clinicians how to identify and treat the disorder.   The 4 percent rate reported by the CDC is encouraging because it is close to what Ron Kessler and colleagues reported as the prevalence of adult ADHD in the population.   CDC correctly points out that little is known about the effects of ADHD medications on pregnancies. Thus, caution is warranted.

Oei et al.'s review of amphetamines concluded: "There is little evidence of amphetamine-induced neurotoxicity and long-term neurodevelopmental impact, as data is scarce and difficult to extricate from the influence of other factors associated with children living in households where one or more parent uses drugs in terms of poverty and neglect. ... We suggest that exposed children may be at risk of ongoing developmental and behavioral impediment, and recommend that efforts be made to improve early detection of perinatal exposure and to increase the provision of early intervention services for affected children and their families"

Bolea-Alamanac et al.'s review of methylphenidate effects concluded: "There is a paucity of data regarding the use of methylphenidate in pregnancy and further studies are required. Although the default medical position is to interrupt any non-essential pharmacological treatment during pregnancy and lactation, in ADHD this may present a significant risk. Doctors need to evaluate each case carefully before interrupting treatment." These words of caution should be heeded by clinicians caring for women of reproductive age.

December 28, 2023

Associations between ADHD and autoimmune diseases

Associations between ADHD and autoimmune diseases

A Norwegian team based at the University of Bergen recently performed a population study using the country's detailed national health registries. With records from more than two and a half million Norwegians, the team examined what, if any, associations could be found between ADHD and nine autoimmune diseases: ankylosing spondylitis, Crohn's disease, iridocyclitis, multiple sclerosis, psoriasis, rheumatoid arthritis, systemic lupus erythematosus, type 1 diabetes, and ulcerative colitis.

After adjusting for age and maternal education, the team found no association between ADHD and five of the nine autoimmune disorders: type 1 diabetes, rheumatoid arthritis, iridocyclitis, systemic lupus erythematosus, and multiple sclerosis. In the case of ankylosing spondylitis, it found no association with males with ADHD, but a negative association with females. Females with ADHD were less likely to have ankylosing spondylitis. The adjusted odds ratio (AOR) was 0.56 (95% CI 0.32-0.96).

Positive associations were found for only three autoimmune diseases. The strongest was for psoriasis, with adjusted odds ratios of 1.6(95% CI 1.5-1.7) for females and 1.3 (95% CI 1.2-1.4) for males. When further adjusted for education, smoking, and body mass index (BMI), however, the adjusted odds ratio for females with ADHD dropped to 1.3 (95% CI 1.0-1.6).

The second-strongest association was with Crohn's disease. But here it was only among women. The odds ratio, in this case, was 1.4 (95% CI 1.2-1.8). Males with ADHD were less likely to have Crohn's disease, with an odds ratio of 0.71 (95% CI 0.54-0.92).

Finally, females with ADHD were slightly more likely to have ulcerative colitis, with a barely significant odds ratio of 1.3 (95% CI 1.1-1.5), while no such association was found for males with ADHD, whose odds ratio was a statistically non-significant 0.9.

Given the large sample size of over two and a half million, this is no underpowered study. It found no association between ADHD and the generic category of autoimmune disorders. Furthermore, it is a stretch to argue that there are any clear and clinically meaningful links between ADHD and any of the specific disorders that were analyzed in this study. The small and often opposite effect sizes may simply reflect limitations with the data (presumed autoimmune disorders were identified based on drugs prescribed), or other unidentified confounding factors.

June 24, 2021

Is There Any Relationship Between Artificial Food Colors and ADHD?

Is there any relationship between artificial food colors and ADHD?

Several meta-analyses have assessed this question by computing the standardized mean difference or SMD statistic.  The SMD is a measure that allows us to compare different studies. For context, the effect of stimulant medication for treating ADHD is about 0.9.  SMDs less than 0.3 are considered low, between 0.3 to 0.6 medium, and anything greater than high.
A 2004 meta-analysis by Schab and Trinh combined the results of fifteen studies with a total of 219 participants and found a small association(SMD = .28, 95% CI .08-.49) between consumption of artificial food colors by children and increased hyperactivity. Excluding the smallest and lowest quality studies further reduced the SMD to .21, and a lower confidence limit of .007 also made it barely statistically significant. Publication bias was indicated by an asymmetric funnel plot. No effort was made to correct the bias.
A 2012 meta-analysis by Nigg et al. combined twenty studies with a total of 794 participants and again found a small effect size (SMD =.18, 95% CI .08-.29). It likewise found evidence of publication bias. Correcting for the bias led to a tiny effect size at the outer margin of statistical significance (SMD = .12, 95% CI .01-.23). Restricting the pool to eleven high-quality studies with 619 participants led to a similarly tiny effect size that fell just outside the 95% confidence interval (SMD = .13, CI =0-.25, p = .053). The authors concluded, "Overall, a mixed conclusion must be drawn. Although the evidence is too weak to justify action recommendations absent a strong precautionary stance, it is too substantial to dismiss."
In 2013 a European ADHD Guidelines Group consisting of 21 researchers (Sonuga-Barke et al.) performed a meta-analysis of eight studies involving 294 participants that examined the efficacy of excluding artificial colors from the diets of children and adolescents as a treatment for ADHD. It found a small-to-medium effect size (SMD = .32, 95% CI .06-.58), with less than one in fifty probability that such a result would occur by chance. Yet "Restricting the probably blinded assessment analysis to the four no/low medication trials reduced the standardized mean difference (0.32) to non-significant levels (95%CI=-0.13, 0.77)."
On balance, the research to date suggests a small effect of artificial food colors in aggravating symptoms of hyperactivity in children, and a small beneficial effect of excluding these substances from the diets of children and adolescents, but the evidence is not very robust. More studies with greater numbers of participants, and better control for the effects of ADHD medications, will be required for a more definitive finding.
In the meantime, given that artificial food colors are not an essential part of the diet, parents should consider excluding them from their children's meals, since doing so is risk-free, and the cost (reading labels) negligible.

June 22, 2021

How reliable are subjective estimates of ADHD medication adherence?

How reliable are subjective estimates of ADHD medication adherence?

A study conducted at Auburn University in Alabama recruited 54 college students to address this question. All had previously been diagnosed with ADHD. All lived independently, and all were taking prescribed ADHD medication. Students with severe comorbid psychiatric conditions were excluded. Three students dropped out, leaving a final sample size of 51.
Each student completed a total of four half-hour assessments, scheduled at monthly intervals. At each first assessment, researchers counted the participant's ADHD medication pills and transferred them to an electronic monitoring bottle-a bottle with a microchip sensor in the cap that automatically tracks the date and time of every opening. This enabled them to compare students' subjective estimates at subsequent assessments with the objective evidence from pill counts and the data output from the electronic monitoring bottles.
Overall, students reported missing about one in four (25 percent) of their prescribed doses. But the objective measures showed they were skipping closer to half their doses. According to pill counts, they were missing 40 percent of their doses, and according to the electronic monitoring bottles, 43 percent. The odds of obtaining such a result due to chance with a sample of size were less than one in a hundred (p < 0.01).
In other words, college students with ADHD significantly overestimate their adherence rates to their medications. The authors concluded, "without additional strategies in place, expecting adolescents and young adults with ADHD to remember a daily task that requires no more than a few seconds to accomplish, such as medication taking, is unrealistic. They suggest using smartphone reminder applications ("apps") and text messaging services.
The authors caution that this was the first such study and that it had a small sample size. Moreover, the study was not randomized. Students responded to advertisements posted on campus, and thus self-selected.
Pending the outcome of larger studies with randomization, the authors suggest that wherever possible, prescribing physicians adopt objective measures of medication adherence, as an aid in ensuring greater efficacy of treatment.

June 20, 2021

How To Best Manage ADHD During Pregnancy to Minimize Risk to Offspring

How can women best manage ADHD during pregnancy to minimize risk to their babies?

Roughly one in thirty adult women have ADHD. Research results indicate that psychostimulants (methylphenidate and amphetamines) offer the most effective course of treatment in most instances. But during pregnancy, such treatment also exposes the fetus to these drugs. Several studies have set out to determine whether such exposure is harmful.

The largest comparison was 5,571 infants exposed to amphetamines and 2,072 exposed to methylphenidate with unexposed infants. It found no increased risks for adverse outcomes due to amphetamine or methylphenidate exposures. Another study studied 3,331 infants exposed to amphetamines, 1,515 exposed to methylphenidate, and 453 to atomoxetine. Comparing these infants to unexposed infants, it found a slightly increased risk of preeclampsia, with an adjusted risk ratio of 1.29 (95% CI 1.11-1.49), but no statistically significant effect for placental abruption, small gestational age, and preterm birth. When assessing the two stimulants, amphetamine, and methylphenidate, together, it found a small increased risk of preterm birth, with an adjusted risk ratio of 1.3 (95% CI 1.10-1.55). There was a statistically significant effect for preeclampsia, placental abruption, or small gestational age. Atomoxetine use was free of any indication of increased risk.

Another study involving 1,591 infants exposed to ADHD medication (mostly methylphenidate) during pregnancy, reported increased risks associated with exposure. The adjusted odds ratio for admission to a neonatal intensive care unit was 1.5 (95% CI 1.3-1.7), and for the central nervous system, disorders were 1.9 (95% CI 1.1-3.1). There was no increased risk for congenital malformations or perinatal death.

Six studies focused on methylphenidate exposure. Two, with a combined total of 402 exposed infants, found no increased risk for malformations. Another, with 208 exposed infants, found a slightly greater risk of cardiovascular malformations, but it was not statistically significant. A fourth, with 186 exposed infants, found no increased risk of malformations but did find a higher rate of miscarriage, with an adjusted hazard ratio of 1.98(95% CI 1.23-3.20). A fifth, with 480 exposed infants, also found a higher rate of miscarriage, with an odds ratio of 2.07 (95% CI 1.51-2.84). But although the sixth, with 382 exposed infants, likewise found an increased risk of miscarriage (adjusted relative risk 1.55 with 95% CI1.03-2.06), it also found an identical risk for women with ADHD who were not on medication during their pregnancies (adjusted relative risk 1.56with 95% CI 1.11-2.20). That finding suggests that all women with ADHD have a higher risk of miscarriage, and that methylphenidate exposure is not the causal factor.

Summing up, while some studies have shown increased adverse effects among infants exposed to maternal ADHD medications, most have not. There are indications that higher rates of miscarriage are associated with maternal ADHD rather than fetal exposure to psychostimulant medications. One study did find a small increased risk of central nervous system disorders and admission to a neonatal intensive care unit. But, again, we do not know whether that was due to exposure to psychostimulant medication or associated with maternal ADHD. If there is a risk, it appears to be a small one.

The question then becomes how to balance that as yet uncertain risk against the disadvantage of discontinuing the effective psychostimulant medication. As the authors of this review conclude. It [ADHD] is associated with significant psychiatric comorbidities for women, including depression, anxiety, substance use disorders, driving safety impairment, and occupational impairment. The gold standard treatment includes behavioral therapy and stimulant medication, namely methylphenidate and amphetamine derivatives. Psychostimulant use during pregnancy continues to increase and has been associated with a small increased relative risk of a range of obstetric concerns. However, the absolute increases in risks are small, and many of the best studies to date are confounded by other medication use and medical comorbidities.

Thus, women with moderate-to-severe ADHD should not necessarily be counseled to suspend their ADHD treatment based on these findings. They advise that when functional impairment from ADHD is moderate to severe, the benefits of stimulant medications may outweigh the small known and unknown risks of medication exposure, and that "If a decision is made to take ADHD medication, women should be informed of the known risks and benefits of the medication use in pregnancy, and take the lowest therapeutic dose possible."

June 18, 2021

What Are The Barriers To Understanding ADHD in Primary Care?

What are the barriers to understanding ADHD in primary care?

A newly-published systematic review by a British team identified48 qualitative and quantitative studies that explored "ADHD in primary care, including beliefs, understanding, attitudes, and experiences." The studies described primary care experiences in the U.S., Canada, Europe, Australia, Singapore, Iran, Pakistan, Brazil, and South Africa.

More than three out of four studies identified deficits in education about ADHD. Of particular concern was the training of primary care providers (PCPs), most of whom received no specific training on ADHD. In most places, a quarter or less of PCPs received such training. Even when such training was provided, PCPs often rated it as inadequate and said they did not feel they could adequately evaluate children with ADHD.

There was even less training for adult ADHD. A 2009 survey of 194 PCPs in Pakistan found that ADHD was not included at all in medical training there and that most learned from colleagues. Half readily admitted to having no competence, and less than one in five were shown to have adequate knowledge about ADHD. In a 2009 survey of 229South African PCPs, only 7 percent reported adequate training in childhood ADHD, and a scant one percent in adult ADHD.

These problems were by no means limited to fewer developed countries. A 2001 U.K. survey of 150 general practitioners found that only 6percent of them had received formal ADHD training. In a 2002 study of 499Finnish PCPs, only half felt confident in their ability to diagnose ADHD. A2005 survey of 405 Canadian PCPs likewise found that only half reported skill and comfort in diagnosis. In a 2009 survey of 400 U.S. primary care physicians, only 13 percent said they had received adequate training. A 2017 study of Swiss PCPs found that only five of the 75 physicians in the sample expressed competence in diagnosis.

Eight studies explored knowledge of DSM (Diagnostic and Statistical Manual of Mental Disorders) criteria and clinical guidelines among PCPs. Only a quarter of PCPs were using DSM criteria, and only one in five were using published guidelines. In a 1999 survey of 401 pediatricians in the U.S.and Canada, only 38 percent reported using DSM criteria. A 2004 survey of 723U. S. PCPs found only 44 percent used DSM criteria. In a 2006 UK study of 40general practitioners, only 22 percent were aware of ADHD criteria. In the same year, a survey of 235 U.S. physicians found that only 22 percent were familiar with ADHD guidelines, and 70 percent used child behavior in the office to make a diagnosis. More encouragingly, a 2010 U.S. study reported that the use of APA (American Psychological Association) guidelines by PCPs had expanded markedly between1999 and 2005, from one in eight to one in two.

Given these facts, it is unsurprising that many PCPs expressed a lack of confidence in treating ADHD. In a 2003 survey of 143 South African general practitioners, two-thirds thought it was difficult to diagnose ADHD in college students. A 2012 U.S. study of 1,216 PCPs found that roughly a third lacked confidence in diagnosis and treatment. More than a third said they did not know how to manage adult ADHD. In a 2015 survey of 59 physicians and138 nurses in the U.S., half lacked confidence in their ability to recognize ADHD symptoms. This was especially pronounced among the nurses. A 2001 U.K.survey of 150 general practitioners found that nine out of ten wanted further training on drug treatment, and more than one out of ten were unwilling to prescribe due to insufficient knowledge.

Misconceptions about ADHD were widespread. In a survey of380 U.S. PCPs, almost half thought ADHD medications were addictive, one in five thought ADHD was "caused by poor diet," more than one in seven thought "the child does it on purpose," and one in ten thought medications can cure ADHD. Some studies reported that many PCPs believed ADHD was related to the consumption of sugary food and drink. Others reported a gender bias. A 2002 U.S. study of395 PCPs found that when presented with boys and girls with parent-reported problems, they were significantly more likely to diagnose ADHD in boys.

A 2010 Iranian study of 665 PCPs found that 82 percent believed children adopted ADHD behavior patterns as a strategy to avoid obeying rules and doing assignments. One-third believed sugary food and drink contributed to ADHD. Only 6 percent believed it could be a lifelong condition. Half blamed dysfunctional families. The aforementioned large 2012 U.S. study similarly found that almost half of PCPs believed ADHD was caused by absent or bad parenting. More than half of 399 Australian PCPs surveyed in 2002 believed inadequate parenting played a key role. In a 2003 study of 48 general practitioners in Singapore, a quarter blamed sugar for ADHD. A 2014 survey of 57French pediatricians found that a quarter thought ADHD was a foreign construct imported into France, and 15 percent attributed it to bad parenting. In all, ten studies reported a widespread belief that ADHD was due to bad parenting, with ratios varying from over one in seven PCPs to more than half. They were particularly likely to attribute hyperactivity to dysfunctional families and to dismiss parents' views of hyperactivity as a medical problem as a way to deflect attention from inadequate parenting. While a third of the studies reported on stigma, the surprise was that it did not seem to play as big a role as expected. A 2012study in the Netherlands found that 74 physicians and 154 non-medical professionals matched by age, sex, and education showed no differences in the level of stigmatization toward ADHD.

On the other hand, the studies identified significant resource constraints limiting more effective understanding, diagnosis, and treatment. Given the complex nature of ADHD, the time required to gain relevant information, especially in the context of competing demands on the attention of PCPs, was a limiting factor. Many studies identified a need for better assessment tools, especially for adults.

Another major constraint was PCP's uneasiness about medication. Studies found a widespread lack of knowledge about treatment options, and more specifically the pros and cons of medication relative to other options. This often led to an unwillingness to prescribe.

Yet another limitation was the difficulties PCPs had in communicating with mental health specialists. One study found that less than one in six PCPs received communications from psychiatrists. Much of this was ascribed to "system failure": discontinuity of care, no central accountability, limited resources, buck-passing. Many PCPs were unsure who to turn to. Another problem is often faulty interactions between schools, parents, children, and providers. Parents often fail to keep appointments. Schools and parents often are less than cooperative in providing information. In a 2004 survey of 786 U.S. school nurses, less than half reported good levels of communication between schools and physicians. Schools and parents often apply pressure on PCPs to issue a diagnosis. In the U.S. survey of 723 PCPs, more than half reported strong pressure from teachers to diagnose ADHD, and more than two-thirds said they were under pressure to prescribe medication.

The authors noted, "The need for education was the most highly endorsed factor overall, with PCPs reporting a general lack of education on ADHD. This need for education was observed on a worldwide scale; this factor was discussed in over 75% of our studies, in 12 different countries, suggesting that lack of education and inadequate education was the main barrier to the understanding of ADHD in primary care.

"In addition, "time and financial constraints affect the opportunities for PCPs to seek extra training and education but also affect the communication with other professionals such as secondary care workers, teachers, and parents." The authors cautioned that only eleven of the 48 studies were published since 2010. Also, because it was a systematic review and not a meta-analysis, there was no way to evaluate publication bias.

They concluded, "Better training of PCPs on ADHD is, therefore, necessary but to facilitate this, dedicated time and resources towards education needs to be put in place by the service providers and local authorities."

June 16, 2021

Mindfulness-Based Cognitive Therapy for Adults with ADHD

Mindfulness-Based Cognitive Therapy for Adults with ADHD

A Dutch study compared the efficacy of mindfulness-based cognitive therapy (MBCT) combined with treatment as usual (TAU), with TAU-only as the control group. MBCT consisted of an eight-week group therapy consisting of meditation exercises (body scan, sitting meditation, mindful movement), psychoeducation about ADHD, and group exercises. TAU consisted of usual treatment in the Netherlands, including medications and other psychological treatments. Sixty individuals were randomly assigned to each group. MBCT was taught in subgroups of 8 to 12 individuals. Patients assigned to TAU were not brought together in small groups. Baseline demographic and clinical characteristics were closely matched for both groups.

Outcomes were evaluated at the start, immediately following treatment, and again after 3 and 6 months using well-validated rating scales. Following treatment, the MBCT + TAU group outperformed the TAU group by an average of 3.4points on the Conner's Adult Rating Scale, corresponding to a standardized mean difference of .41. Thirty-one percent of the MBCT + TAU group made significant gains, versus 5% of the TAU group. 27% of MBCT +TAU patients scored a symptom reduction of at least 30 percent, as opposed to only 4% of TAU patients. Three and six-month follow-up effects were stable, with an effect size of .43.

The authors concluded, "that MBCT has significant benefits to adults with ADHD up to 6 months after post-treatment, about both ADHD symptoms and positive outcomes." Yet in their section on limitations, they overlook a potentially important one. There was no active placebo control. Those who were undergoing TAU-only were aware that they were not doing anything different from what they had been doing before the study. Hence, no substantial placebo response would be expected from this group during the intervention period (post-treatment they were offered an opportunity to undergo MBCT). Moreover, MBCT + TAU participants were gathered into small groups, whereas TAU participants were not. We, therefore, have no way of knowing what effect group interaction had on the outcomes because it was not controlled for. So, although these results are intriguing and suggest that further research is worthwhile, the work is not sufficiently rigorous to definitively conclude that MBCT should be prescribed for adults with ADHD.

June 8, 2021

Is Cognitive Behavior Therapy Effective for Older Adults with ADHD?

Is Cognitive Behavior Therapy Effective for Older Adults with ADHD?

Though there have been numerous studies on the efficacy of cognitive-behavioral therapy (CBT) for ADHD symptoms in children, adolescents, and adults, few have examined efficacy among adults over 50. A new study begins to fill that void.

Psychiatric researchers from the New York University School of Medicine, Massachusetts General Hospital, and Pfizer randomly assigned 88 adults diagnosed with elevated levels of ADHD to one of two groups. The first group received 12 weeks of CBT targeting executive dysfunction - a deficiency in the ability to properly analyze, plan, organize, schedule, and complete tasks. The second group was assigned to a support group, intended to serve as a control for any effects arising from participating in group therapy. Each group was split into subgroups of six to eight participants. One of the CBT subgroups was run concurrently with one of the support-only subgroups and matched on the percent receiving ADHD medications.

Outcomes were obtained for 26 adults aged 50 or older (12 in CBT and 14 in support) and compared with 55 younger adults (29 in CBT and 26 in support). The mean age of the younger group was 35 and of the older group 56. Roughly half of the older group, and 3/5ths of the younger group, were on medication. Independent("blinded") clinicians rated symptoms of ADHD before and after treatment.

In the blind structured interview, both inattentive scores and executive function scores improved significantly and almost identically for both older and younger adults following CBT. When compared with the controls(support groups), however, there was a marked divergence. In younger adults, CBT groups significantly outperformed support groups, with mean relative score improvements of 3.7 for inattentive symptoms and 2.9 for executive functioning. In older adults, however, the relative score improvements were only 1.1 and0.9 and were not statistically significant.

Given the non-significant improvements over placebo, the authors' conclusion that "The results provide preliminary evidence that CBT is an effective intervention for older adults with ADHD" is premature. As they note, a similar large placebo effect was seen in adults over 50 in a meta-analysis of CBT for depression, rendering the outcomes non-significant. Perhaps structured human contact is the key ingredient in this age group. It may also be, as suggested by the positive relative gains on six of seven measures, that CBT has a small net benefit over placebo, which cannot be validated with such a small sample size. Awaiting results from studies with larger sample sizes, it is, for now, impossible to reach any definitive conclusions about the efficacy of CBT for treating adults over 50.

June 6, 2021

Can ADHD be Treated with Fish Oil?

Can ADHD be Treated with Fish Oil?

If you've been reading my blogs about ADHD, you know that I play by the rules of evidence-based medicine. My view is that the only way to be sure that a treatment 'works' is to see what researchers have published in scientific journals. The highest level of evidence is a meta-analysis of randomized controlled clinical trials.  For my lay readers, that means that many rigorous studies have been conducted and summarized with a sophisticated mathematical method. If you are interested in fish oil as a treatment for ADHD, there is some good news.  Many good studies have been published and these have been subjected to meta-analysis. To be more exact, we're discussing omega-3 polyunsaturated fatty acids (PUF As), which are found in many fish oils. Omega-3 PUF As reduces inflammation and oxidative stress, which is why they had been tested as treatments for ADHD. When these studies were meta-analyzed, it became clear that omega-3 PUFAs high in eicosapentaenoic acid (EPA) helped to reduce ADHD symptoms. For details see: Bloch, M. H. and J. Mulqueen (2014). "Nutritional supplements for the treatment of ADHD." Child Addles Psychiatry Clin N Am23(4): 883-897. So, if omega-3 PUF helps reduce ADHD symptoms, why are doctors still prescribing ADHD drugs? The reason is simple. Omega-3supplements work, but not very well. On a scale of one to 10 where 10 is the best effect, drug therapy scores 9 to 10but omega-3 therapy scores only 2.  Some patients or parents of patients might want to try omega-3 therapy first, in the hopes that it will work well for them. That is a possibility, but if that is your choice, you should not delay the more effective drug treatments for too long in the likely event that omega-3 therapy is not sufficient.  What about combining ADHD drugs with omega-3 supplements? We don't know. I hope that future research will see if combined therapy might reduce the number of drugs required for each patient. Keep in mind that the treatment guidelines from professional organizations point to ADHD drugs as the first-line treatment for ADHD. The only exception is for preschool children where medication is only the first-line treatment for severe ADHD; the guidelines recommend that other preschoolers with ADHD be treated with non-pharmacologic treatments, when available. You can learn more about non-pharmacologic treatments for ADHD from a book I recently edited: Faraone, S. V. & Antshel, K. M. (2014). ADHD: Non-Pharmacologic Interventions. Child Addles psychiatry Clin N Am 23, xiii-xiv.

May 29, 2021

Does the Age of Onset Matter When Diagnosing ADHD in Older Adults?

Psychotherapy and ADHD: How a Harvard Professor Helped his Patients

Professor Larry Seidman is world-renowned for his neuropsychology and neuroimaging research. In addition to all of his creative science, he has found the time to create what he calls "Neuropsychological Informed Strategic Psychotherapy (NISP)in Teenagers and Adults with ADHD."

Let's start with what NISP is not. NISP is not cognitive behavior therapy (CBT). CBT emphasizes teaching patients to identify thinking patterns that lead to problem behaviors. NISP describes how the interpersonal interaction we call psychotherapy can help patients increase self-regulation and self-control. NISP treatments vary in duration from brief psycho-educational interventions of one to five sessions to much longer-term therapies of indefinite duration. The duration of therapy is tailored to the needs and goals of the individual. The methods of NISP can be adaptively applied to well-known therapy modalities such as CBT and family therapy.

By creating a solid therapeutic alliance, NISP improves adherence to medications and addresses ADHD's psychiatric comorbidities and functional disabilities. NISP is "neuropsychological informed" because it follows a comprehensive neuropsychological assessment of strengths and weaknesses. This leaves the therapist with an understanding of the patient's personal experience of ADHD, the meaning of the disorder, how it affects self-esteem, and how cognitive deficits limit the ability to self-regulate and adapt to changing circumstances. Attending to the patient's strengths is a key feature of Prof. Seidman's method.

ADHD is a serious disorder and it usually has serious consequences. But ADHD people also have strong points in their character and their neuropsychological skills. These sometimes get lost in assessments of ADHD but, as Dr. Seidman indicates, by addressing strengths, patient outcomes can be improved. A NISP assessment also seeks to learn about the psychological themes that underlie each patient's story. He gives the all too common example of the patients who view themselves as failed children who have not tried hard enough to succeed.

A frank discussion of neuropsychological test results can be the first step to helping patients reconceptualize their past and move on to an adaptive path of self-understanding and self-regulation. Prof. Seidman's approach seems sensible and promising. As he recognizes, it has not yet, however, been subject to the rigorous tests of evidenced-based medicine. With this in mind, I would not recommend using it as a replacement for evidence-based treatment. That said, if you are a psychotherapist who treats ADHD people, read Prof. Seidman's paper. It will give you useful insights that will help your patients.

May 23, 2021

Other Myths About ADHD


Myth: ADHD is an American disorder.
Those who claim ADHD is an American disorder believe that ADHD is due to the pressures of living in a fast-paced, competitive American society.   Some argue that if we lived in a simpler world, ADHD would not exist.  

Fact:  ADHD occurs throughout the world.

Wherever scientists have searched for ADHD, they have found it.  They have done this by going to different countries, and speaking to people in the community to diagnose them with or without ADHD.   These studies show that ADHD occurs throughout the world and that the percentage of people having ADHD does not differ between the United States and the rest of the world.   Examples of where ADHD has been found include  Australia, Brazil, Canada, China, Colombia, Finland, Germany, Iceland, Israel, Italy, Japan, New Zealand, Spain, Sweden, Taiwan, The Netherlands, and Ukraine.   ADHD is not an American disorder.

Myth: A child who sits still to watch TV or play video games cannot have ADHD.
Many parents are puzzled that their child can sit still to watch TV or play video games for hours, but that same child cannot sit still for dinner or stay at their desk for long to do homework.  Are these children faking ADHD symptoms to get out of homework?

Fact:  ADHD does not necessarily interfere with playing video games or watching TV.

Because children cannot turn their ADHD on and off to suit their needs, it does seem odd that a child who is typically hyperactive and inattentive can sit for hours playing a video game.  But this ability of ADHD children fits in very well with scientific facts about ADHD. First, you probably understand the effects of rewards and punishment on behavior.  If your behavior is rewarded, you are likely to do it again.  If it is punished, you will avoid that behavior in the future.  Rewards that have the strongest effect on our behavior are large and will occur soon. For example, consider these two choices:
a)      if you listen to a boring one-hour lecture, I will pay you $100 immediately after the lecture
b)      if you listen to a boring one-hour lecture, I will pay you $110 one year after the lecture
Choice (a) is more appealing than choice (b).  Most people will not think it is worthwhile to wait one year for $10.  We say they have 'discounted' the $10 to $0.
Now consider the choices:
c)      if you listen to a boring one-hour lecture, I will pay you $100 immediately after the lecture
d)     if you listen to a boring one-hour lecture, I will pay you $2,000 one year after the lecture

Choice (d) is more appealing than choice (c).  Most people will wait one year for$2,000.   It is obvious here is that if I want the best chance of having you watch a lecture, I should offer you a large sum of money immediately after the lecture. What is not so obvious is that people vary a great deal in the degree to which they are affected by rewards that are either small or distant in the future.   For some people, getting $2,000in one year is almost like getting nothing at all.  We say that such people are not sensitive to distant rewards.

What does this have to do with ADHD and video games?  Well, people with ADHD are usually not very sensitive to weak or distant rewards.  To affect the behavior of a person with ADHD, the reward needs to be immediate and fairly large.  When a child with ADHD sits down to do homework, the potential reward is getting a good grade on their report card, but they won't receive that grade for weeks or months, so it is very distant.  Thus, it is not surprising that the possibility of that reward cannot control the child's behavior.  In contrast, video games are created so that players are rewarded very frequently by winning points or completing one of the many levels one must pass to finally complete the game.  Because playing well is also rewarded by friends, the video game rewards are strong and immediate, which makes it easy for people with ADHD to sit still and play for long periods.

 Myth: ADHD disappears in adulthood.
Until the 1990s, it was commonly believed that children grew out of ADHD.  The reason for this is not clear.  Some theories about ADHD suggested that ADHD children had a lag in brain development, and that they would make up for that lag during adolescence.  So ADHD was seen as a delay in brain development that could be overcome.   The idea that children routinely recovered from ADHD was so strong that many insurance companies would not pay for the ADHD treatment of adults.

Fact: In the majority of cases, ADHD persists into adulthood.
This myth about ADHD has been proven wrong by studies that diagnosed ADHD in children and then examined it many years later than in adults.  These studies showed that, although there was some recovery from ADHD, about two-thirds of cases persisted into adulthood. The studies also taught us that ADHD symptoms tend to change with age.  The extreme and disruptive hyperactivity of many ADHD children gets somewhat better by adulthood, as do some symptoms of impulsivity.   In contrast, inattentive symptoms do not decrease much with age.

 Myth: People with ADHD cannot do well in school or succeed in life.
This myth is based on several facts: 1) ADHD affects many aspects of life; 2) ADHD impairs thinking and behavior and 3) for most people, ADHD is a lifelong disorder.   Altogether, doesn't this mean that people with ADHD won't succeed in life?

Fact: People with ADHD can succeed and live productive lives.
There are two reasons why people with ADHD can succeed in life. The first is obvious.  Although treatments for ADHD are not perfect, they can eliminate many of the obstacles that would otherwise make it difficult for ADHD patients to do well in school or on the job.  But, more importantly, having ADHD is only one of many facts about a person's life.   Some ADHD people have other skills or traits that help them compensate for their ADHD.  For example, if you have a high level of intelligence, an engaging personality, or excellent athletic skills, you can do well despite having ADHD.   Consider Michael Phelps, who broke so many Olympic swimming records. He was diagnosed with ADHD at age 9 and took Ritalin to help his hyperactivity.   James Carville has ADHD, but he completed law school and helped Bill Clinton become President of the United States.  Cammi Granato's ADHD did not stop her from becoming captain of the United  States Olympic ice hockey team, and Ty Pennington's ADHD did not stop him from becoming a  star on TV.

 Myth: ADHD does not affect highly intelligent people
The mistake behind this myth is that it assumes that being very intelligent protects people from having ADHD.  It's true that if you are highly intelligent, you can use that intelligence to compensate for some ADHD' effects, but does high intelligence completely protect a person from ADHD?

Fact: People with ADHD can succeed and live productive lives.
When my colleagues and I studied this question, we found clear evidence that high intelligence does not completely protect people from ADHD. Like people who don't have ADHD, having high intelligence will help Alderpeople do better than ADHD people who are not smart.  But when we compared highly intelligent Alderpeople with highly intelligent non-ADHD people, we found that the highly intelligent ADHD people had many of the impairing problems that are known to be associated with ADHD.  For details about these problems, see Complications of ADHD.  In another study, we compared ADHD adults who had received straight A grades in high school, with non-ADHD people who had achieved the same grades.  Despite their good grades, these ADHD adults were not doing as well in their jobs and not earning as much income as the non-ADHD adults.  And ADHD also has an impact at every level of education.  As you can see from the figure, even for people with college degrees, having ADHD lowers your chances of being employed.

May 19, 2021

Are Nonpharmacologic Treatments for ADHD Useful?

Are Nonpharmacologic Treatments for ADHD Useful?

There are several very effective drugs for ADHD, and those treatment guidelines from professional organizations view these drugs as the first line of treatment for people with ADHD. The only exception is for preschool children where medication is only the first line of treatment for severe ADHD; the guidelines recommend that other preschoolers with ADHD be treated with non-pharmacologic treatments, when available. Despite these guidelines, some parents and patients have been persuaded by the media or the Internet that ADHD drugs are dangerous and that non-drug alternative are as good or even better. Parents and patients may also be influenced by media reports that doctors overprescribe ADHD drugs or that these drugs have serious side effects. Such reports typically simplify and/or exaggerate results from the scientific literature. Thus, many patients and parents of ADHD children are seeking non-drug treatments for ADHD. What are these non-pharmacologic treatments and do they work? My next series of blogs will discuss each of these treatments in detail. Here I'll give an overview of my evidenced-based taxonomy of non-pharmacologic treatments for ADHD described in more detail in a book I recently edited (Faraone, S. V. &Antshel, K. M. (2014). ADHD: Non-Pharmacologic Interventions. Child Adolesc Psychiatry Clin N Am 23, xiii-xiv.). I use the term "evidence-based" in the strict sense applied by the Oxford Center for Evidenced Based Medicine (OCEBM; Most of the non-drug treatments for ADHD fall into three categories: behavioral, dietary, and neurocognitive. Behavioral interventions include training parents to optimize methods of reward and punishment for their ADHD child, teaching ADHD children social skills, and helping teachers apply principles of behavior management in their classrooms. Cognitive behavior therapy is a method that teaches behavioral and cognitive skills to adolescent and adult ADHD patients. Dietary interventions include special diets that exclude food coloring or eliminate foods believed to cause ADHD symptoms. Other dietary interventions provide supplements such as iron, zinc, or omega-3 fatty acids.  The neurocognitive interventions typically use a computer-based learning setup to teach ADHD patients cognitive skills that will help reduce ADHD symptoms. There are two metrics to consider when thinking about the evidence base for these methods. The first is the quality of the evidence. For example, a study of 10 patients with no control group would be a low-quality study, but a study of 100 patients randomized to either a treatment or control group would be of high quality and the quality would be even higher if the people's rating patient outcomes did not know who was in each group. The second metric is the magnitude of the treatment effect. Does the treatment dramatically reduce ADHD symptoms, or does it have only a small effect? This metric is only available for high-quality studies that compare people treated with the method and people treated with a 'control' method that is not expected to affect ADHD. I used a statistical metric to quantify the magnitude of the effect. Zero means no effect, and larger numbers indicate better effects on treating ADHD symptoms. For comparison, the effect of stimulant drugs for ADHD is about 0.9, which is derived from a very strong evidence base.  The effects of dietary treatments are smaller, about 0.4 to 0.5, but because the quality of the evidence is not strong, these results are not certain and the studies of food color exclusions apply primarily to children who have high intakes of such colorants. In contrast to the dietary studies, the evidence base for behavioral treatments is excellent, but the effects of these treatments on ADHD symptoms are very small, less than 0.1.  Supplementation with omega-3 fatty acids also has a strong evidence base, but the magnitude of the effect is also small (0.1 to 0.2). The neurocognitive treatments have modest effects on ADHD symptoms (0.2 to 0.4) but their evidence base is weak. This review of non-drug treatments explains why ADHD drug treatments are usually used first. The evidence base is stronger, and they are more effective in reducing ADHD symptoms. There is, however, a role for some non-drug treatments. I'll be discussing that in subsequent blog posts. See more evidence-based information about ADHD at

May 17, 2021

Myths About the Treatment of ADHD

Myths About The Treatment of ADHD

Myth:  ADHD medications "anesthetize" ADHD children.
The idea here is that the drug treatment of ADHD is no more than a chemical straightjacket intended to control a child's behavior to be less bothersome to parents and teachers. After all, everyone knows that if you shoot up a person with tranquilizers, they will calm down.

Fact:  ADHD medications are neither anesthetics nor tranquilizers.

The truth of the matter is that most ADHD medications are stimulants. They don't anesthetize the brain; they stimulate it. By speeding up the transmission of dopamine signals in the brain, ADHD medications improve brain functioning, which in turn leads to an increased ability to pay attention and control behavior.  The non-stimulant medications improve signaling by norepinephrine. They also improve the brain's ability to process signals. They are not sedatives or anesthetics. When taking their medication, ADHD patients can focus and control their behavior to be more effective in school, work, and relationships.  They are not "drugged" into submission.

Myth: ADHD medications cause drug and alcohol abuse
We know from many long-term studies of ADHD children that when they reach adolescence and adulthood, they are at high risk for alcohol and drug use disorders. Because of this fact, some media reports have implied that their drug use was caused by treatment of their ADHD with stimulant medications.

Fact: ADHD medications do not cause drug and alcohol abuse
Some ADHD medications indeed use the same chemicals that are found in street drugs, such as amphetamine.  But there is a very big difference between these medications and street drugs. When street drugs are injected or snorted, they can lead to addiction, but when they are taken in pill form as prescribed by a doctor, they do not cause addiction. When my colleagues and I examined the world literature on this topic, we found that rather than causing drug and alcohol abuse, stimulant medicine protected ADHD children from these problems later in life. One study from researchers at Harvard University and the Massachusetts General Hospital found that the drug treatment of ADHD reduced the risk for illicit drug use by84 a percent. These findings make intuitive sense. These medicines reduce the symptoms of the disorder that lead to illicit drug use. For example, an impulsive ADHD teenager who acts without thinking is much more likely to use drugs than an ADHD teen whose symptoms are controlled by medical drug treatment. After we published our study, other work appeared. Some of these studies did not agree that ADHD medications protected ADHD people from drug abuse, but they did not find that they caused drug abuse.

Myth:  Psychological or behavioral therapies should be tried before medication.  
Many people are cautious about taking medications, and that caution is even stronger when parents consider treatment options for their children.  Because medications can have side effects, shouldn't people with ADHD try to talk therapy before taking medicine?

Fact:  Treatment guidelines suggest that medication is the first-line treatment.
The problem with trying talk or behavior therapy before medication is that medication works much better.  For ADHD adults, one type of talk therapy(cognitive behavioral therapy) is recommended, but only when the patient is also taking medication.  The multimodal treatment of ADHD (MTA) study examined this issue in ADHD children from several academic medical centers in the United States. That study found that treating ADHD with medication was better than treating it with behavior therapy. Importantly, behavior therapy plus medication was no more effective than medication alone. That is why treatment guidelines from the American Academy of Pediatrics and the American Academy of Children and Adolescents recommend medicine as a first-line treatment for ADHD, except for preschool children. ADHD medications indeed have side effects, but these are usually mild and typically do not interfere with treatment.  And don't forget about the risks that a patient faces when they do not use medications for ADHD.  These untreated patients are at risk for worsening ADHD symptoms and complications.

Myth: Brain abnormalities of ADHD patients are caused by psychiatric medications
A large scientific literature shows that ADHD people have subtle problems with the structure and function of their brains.  Scientists believe that these problems are the cause of ADHD symptoms. Critics of ADHD claim that these brain problems are caused by the medications used to treat ADHD.  Who is right?

Fact: Brain abnormalities are found in never medicated ADHD patients.
Alan Zametkin, a scientist at the US National Institute of Mental Health, was the first to show brain abnormalities in ADHD patients who had never been treated for their ADHD.  He found that some parts of the brains of ADHD patients were underactive. His findings could not be due to medication because the patients had never been medicated. Since his study, many other researchers have used neuroimaging to examine the brains of ADHD patients. This work confirmed Dr. Zametkin’s observation of abnormal brain findings in unmediated patients. Reviews of the brain imaging literature have concluded that the brain abnormalities seen in ADHD cannot be attributed to ADHD medications.

May 15, 2021

Myths About The Diagnosis of ADHD


Myth: The ADHD diagnosis is very much "in the eye of the beholder."
This is one of many ways in which the ADHD diagnosis has been ridiculed in the popular media. The idea here is that because we cannot diagnose ADHD with an objective brain scan or a blood test, the diagnosis is "subjective" and subject to the whim and fancy of the doctor making the diagnosis.

Fact:  The ADHD diagnosis is reliable and valid.
The usefulness of a diagnosis does not depend on whether it came from a blood test, a brain test, or from talking to a patient. A test is useful if it is reliable, which means that two doctors can agree on who does and does not have the disorder, and if it is valid, which means that the diagnosis predicts something important to the doctor and patient, such as whether the patient will respond to a specific treatment. Many research studies show that doctors usually agree about who does and does not have ADHD. This is because we have very strict rules that one must use to make a diagnosis. Much work over many decades has also shown ADHD to be a valid diagnosis. For details see: Faraone, S. V. (2005). The scientific foundation for understanding attention-deficit/hyperactivity disorder as a valid psychiatric disorder. Eur Child Adolesc Psychiatry, 14, 1-10. The short story is that the diagnosis of ADHD is very useful for predicting what treatments will be effective and what types of problems ADHD patients are likely to experience in the future.

Myth: ADHD is not a medical disorder.  It's just the extreme of normal childhood energy
Mental health professionals use the term "disorder" to describe ADHD, but others argue that what we view as a disorder named ADHD is simply the extreme of normal childhood energy. After all, most healthy children run around and don't always listen to their parents. Doesn't the ADHD child or adult simply have a higher dose of normal behavior?

Fact: Doctors have good reasons to describe ADHD as a disorder
The idea that the extreme of normal behavior cannot be a disorder is naïve. Consider hypertension(high blood pressure). Everyone has blood pressure, but when blood pressure exceeds a certain value, doctors get worried because people with high values are at risk for serious problems, such as heart attacks. Consider depression. Everyone gets sad from time to time, but people who are diagnosed with depression cannot function in normal activities and, in the extreme, are at risk of killing themselves. ADHD is not much different from hypertension or depression. Many people will show some signs of ADHD at some times, but not all have a "disorder." We call ADHD a disorder not only because the patient has many symptoms, but also because that patient is impaired, which means that they cannot carry out normal life activities. For example, the ADHD child cannot attend to homework or the ADHD adult cannot hold a job, despite adequate levels of intelligence. Like hypertension, untreated ADHD can lead to serious problems such as failing in school, accidents, or an inability to maintain friendships. These problems are so severe that the center for Disease Control described ADHD as  "serious public health problem."

Myth: The ADHD diagnosis was developed to justify the use of drugs to subdue the behaviors of children.
This is one of the more bizarre myths about ADHD. The theory here is that to sell more drugs, pharmaceutical companies invented the diagnosis of ADHD to describe normal children who were causing some problems in the past.

Fact: ADHD was discovered by doctors long before ADHD medications were discovered.
People who believe this myth do not know the history of ADHD. In 1798, long before there were any drugs for ADHD, Alexander Crichton, a Scottish doctor, described a "disease of attention," which we would not call ADHD.ADHD symptoms were described by a German doctor, Heinrich Hoffman, in1845 and by a British doctor, George Still, in 1902. Each of these doctors found that inattentive and overactive behaviors could lead to a problem that should be of concern to doctors. If they had had medications to treat ADHD, they probably would have prescribed them to their patients. But a medication for ADHD was not discovered until 1937 and even then, it was discovered by accident. Dr. Charles Bradley from Providence, Rhode Island had been doing brain scanning studies of troubled children in a hospital school. The scans left the children with headaches that Dr. Bradley thought would be relieved by an amphetamine drug. When he gave this drug to the children after the scan, it did not help their headaches. However, the next day, their teachers reported that the children were attending and behaving much better in the classroom. Dr. Bradley had accidentally discovered that amphetamine was very helpful in reducing ADHD symptoms, and amphetamine drugs are commonly used to treat ADHD today. So, as you can see, the diagnosis of ADHD was not "invented" by anyone; it was discovered by doctors long before drugs for ADHD were known.

Myth: Brain scans or computerized tests of brain function can diagnose ADHD.
Someday, this myth may become fact, but for now, and shortly it is a solid myth. You may think this is strange. After all, we know that ADHD is a brain disorder and that neuroimaging studies have documented structural and functional abnormalities in the brains of patients with ADHD. If ADHD is a biological disorder, why don’t we have a biological test for the diagnosis?

Fact:  No brain test has been shown to accurately diagnose ADHD.
ADHD is a biologically based disorder, but there are many biological changes and each of these is so small that they are not useful as diagnostic tests. We also think that there are several biological pathways to ADHD. That means that not all ADHD patients will show the same underlying biological problems. So for now, the only officially approved method of diagnosing ADHD is by asking patients and/or their parents about ADHD symptoms as described in the American Psychological Association's Diagnostic and Statistical Manual

May 13, 2021

More Data About Gifted People with ADHD

More Data About Gifted People with ADHD

I recently came across a paper from Tom Brown that adds to the growing scientific literature about smart people with ADHD. Dr. Brown's study measured executive functions in 157 ADHD adults with an intelligence quotient (IQ) in the top 9 percent of the population. The executive functions of the brain regulate cognitive processes in a manner that allows for the effective planning and execution of behaviors.

We know from many studies that both children and ADHD have deficits in executive functions, which impair their ability to manage time and keep themselves organized. Dr. Brown extends that literature by showing that three out of four ADHD adults with high IQ scores were significantly impaired on tests of executive functioning. They had problems in many areas: working memory, processing speed, and auditory-verbal working memory relative.

The lesson from this literature is clear. Smart people can have ADHD. Their high IQs will help them do better than the average person with ADHD, but they may not achieve their potential without appropriate diagnosis and treatment.

For more evidence-based info about adult ADHD, go to

May 9, 2021

Love, Sex and ADHD

Love, Sex and ADHD

As a researcher who has devoted most of the past three decades to studying ADHD, I am surprised (and somewhat embarrassed) to see how little research has focused on how ADHD affects the romantic side of life. There are over 25,000 articles about ADHD listed, but only a few have provided data about love, sex, and ADHD. Brunner and colleagues studied ADHD symptoms and romantic relationship quality in 189 college students. Those students who had high levels of both hyperactivity-impulsivity and inattentiveness reported that the quality of their romantic relationships was relatively low compared with students who had low levels of ADHD symptoms. Another study of 497 college students found that ADHD symptoms predicted greater use of maladaptive coping strategies in romantic relationships and less romantic satisfaction. A study of young adults compared conflict resolution and problem-solving in romantic couples. It found that ADHD symptoms were associated with greater negativity and less positivity during a conflict resolution task, and that higher symptoms predicted less relational satisfaction. But this was not true, as the ADHD member of the couple only had inattentive symptoms, which suggests that the severity of ADHD symptoms might drive relationship problems. Unlike the studies of adults, the romantic relationships of adolescents with and without ADHD did not differ in levels of aggression or relationship quality, although only one study addressed this issue.
What about sex? 
The study of adolescents found that irrespective of gender, adolescents with ADHD had nearly double the number of lifetime sexual partners. That finding is consistent with Barkley's follow-up study of ADHD children. He and his colleagues found that ADHD predicted early sexual activity and early parenthood. Similar findings were reported by Flory and colleagues in a retrospective study of young adults. Childhood ADHD predicted earlier initiation of sexual activity and intercourse, more sexual partners, more casual sex, and more partner pregnancies. When my colleagues and I studied 1001 adults in the community, we found that adults with ADHD endorsed less stability in their love relationships, felt less able to provide emotional support to their loved ones, experienced more sexual dysfunction, and had higher divorce rates. The research literature about love, sex, and ADHD is small, but it is consistent.

May 5, 2021

Is ADHD a Serious Condition?

Is ADHD a Serious Condition?

In the popular media, ADHD has sometimes been portrayed as a minor condition or not a disorder at all. It is easy to find websites claiming that ADHD is an invention of the medical profession and that the symptoms used to diagnose the disorder are simply normal behaviors that have been "medicalized". These claims are wrong. They miss the main point of any psychiatric diagnostic process, which is to identify people who experience distress or disability due to a set of well-defined symptoms. So, does ADHD cause serious distress and disability? It is a serious psychiatric condition? To illustrate the strong evidence base for the "Yes" answer to that question, my colleagues and I constructed this infographic for our "Primer" about ADHD, describes the many ways in which the symptoms of ADHD impact and impair the lives of children, adolescents, and adults with the disorder. We divided these 'impacts' into four categories: other disorders (both psychiatric and medical), psychological dysfunction, academic and occupational failure, social disability, and risky behaviors. Let's start with other health problems. We know from many studies that have followed ADHD children into adolescence and adulthood that having the disorder puts patients at risk for several psychiatric disorders, addictions, criminality, learning disabilities, and speech/language disorders. ADHD even increases the risk for-psychiatric diseases such as obesity, hypertension, and diabetes. Perhaps most worrisome is that people with ADHD have a small increased risk for premature death. This increased risk is due in part to their having other psychiatric and medical conditions and also to their risky behaviors which, as research documents, lead to accidents and traumatic brain injuries. In the category of psychological dysfunction,' we highlighted emotional dysregulation, which makes ADHD people quick to anger or fail to tame extreme emotions. Other serious psychological issues are low self-esteem and increased thoughts of suicide, which lead to more suicide attempts than for people without ADHD. This increased risk for suicide is small, but it is real. A more prevalent impact of ADHD is the broad category of social disability, which includes marital discord, poor parenting, legal problems, arrests, and incarceration. This typically starts in youth with poor social adjustment and conflict with parents, siblings, and friends. Another common impact of ADHD is on academic and vocational pursuits. ADHD youth are at risk for underachievement in school, repeating grades, and dropping out. As adults, they are more likely to be unemployed or underemployed, which leads to them having lower incomes than expected for their level of school achievement. So, don't believe anyone who claims that ADHD is not a disorder or is only a mild one. To be sure, there is a wide range of impairments among people with ADHD but, in the absence of treatment, they are at risk for adverse outcomes. Fortunately, the medications that treat ADHD have been documented to reduce this risk, which is why they are typically the first-line treatment for most people with ADHD.

May 3, 2021

Is ADHD A Serious Conidtion?

How Serious is ADHD?

The US Center for Disease Control's (CDC)review of ADHD starts with the statement: "Attention-deficit/hyperactivity disorder (ADHD) is a serious public health problem affecting many children and adults" ( My colleagues and I recently reviewed the ADHD literature. That let us describe ADHD as "... a seriously impairing, often persistent neurobiological disorder of high prevalence..." (Faraone et al., 2015). The figure 1, which comes from that paper, provides an overview of the lifetime trajectory of ADHD-associated morbidity.

Especially compelling data about ADHD and injuries comes from a recent paper, in Lancet Psychiatry, which used the Danish national registers to follow a cohort of 710,120 children (Dalsgaard et al., 2015a).   Compared with children not having ADHD, those with ADHD were 30% more likely to sustain injuries than other children.  Pharmacotherapy for ADHD reduced the risk for injuries by 32% from 5 to 10 years of age. Pharmacotherapy for ADHD reduced emergency room visits by 28.2% at age 10and 45.7% at age 12.    

These results are shown in Figure 2, taken from the publication.

Especially compelling data about ADHD and injuries comes from a recent paper, in Lancet Psychiatry, which used the Danish national registers to follow a cohort of 710,120 children (Dalsgaard et al., 2015a).   Compared with children not having ADHD, those with ADHD were 30% more likely to sustain injuries than other children.  Pharmacotherapy for ADHD reduced the risk for injuries by 32% from 5 to 10 years of age. Pharmacotherapy for ADHD reduced emergency room visits by 28.2%at age 10and 45.7% at age 12.    

These results are shown in Figure2, taken from the publication.  The Figure compares the prevalence of injuries among three groups.  ADHD children treated with medication, ADHD children not treated with medication, and children without ADHD.  The Figure shows how ADHD risk for injuries occurs for all age groups. It also shows how the risk for injuries drops with treatment so that by age 12, the prevalence of injuries among treated ADHD children is the same as the prevalence of injuries for children without ADHD.

Documented examples of ADHD-associated injuries which impact day-to-day functioning include severe burns (Fritz and Butz, 2007), dental injuries (Sabuncuoglu, 2007), penetrating eye injuries (Bayar et al., 2015), the hospital treated injuries (Hurtig et al., 2013), and head injuries (DiScala et al., 1998).  In one study (DiScala et al., 1998), when compared to other children admitted to the hospital for injuries, ADHD children were more likely to sustain injuries in multiple body regions (57.1% vs 43%), sustain head injuries (53% vs 41%), and to be severely injured as measured by the Injury Severity Score (12.5% vs5.4%) and the Glasgow Coma Scale (7.5% vs 3.4%).

Injuries are a substantial cause of ADHD-associated premature death.  This assertion comes from the work of Dalsgaard et al. (2015b)based on the same Danish registry discussed above.   In this second study, ADHD was associated with an increased risk for premature death and 53% of those deaths were due to injuries.  They reported the risk for premature death in three age groups: 1-5, 6-17, and >17.  For all three age groups, they found a greater risk for death in the ADHD group. For ages 6 to 17 and greater than 17. The ADHD-associated risk for mortality remained significant after excluding individuals with antisocial or substance use disorders.

There are currently no data about the effect of ADHD treatment on ADHD-associated premature death.  We do, however, know from the data reviewed above that ADHD treatment reduces injuries and that half the deaths in the ADHD group were due to injuries.  From this, we infer that ADHD treatments could reduce the risk of ADHD-associated premature death.

Two other ADHD-associated mobilities, obesity and cigarette smoking, have clear medical consequences.  In a meta-analysis of 42 cross-sectional studies comprising 48,161 people with ADHD and 679,975 controls, my colleagues and I reported that the pooled prevalence of obesity was increased by about 40% in ADHD children compared with non-ADHD children and by about 70% in ADHD adults compared with non-ADHD adults(Cortese et al.,2015). The association between ADHD and obesity was significant for ADHD medication-naïve subjects but not for those medicated for ADHD, which suggests that medication reduces the risk for obesity.  

Likewise, a meta-analysis of 27 longitudinal studies assessed the risk for several addictive disorders with sample sizes ranging from 4142 to 4175 for ADHD and 6835 to 6880 for non-ADHD controls (Lee et al., 2011).  Children with ADHD were at higher risk for disorders of abuse or dependence on nicotine, alcohol, marijuana, cocaine, and other unspecified substances.  Another meta-analysis (42 studies totaling, 2360 participants) showed that medications for ADHD reduced the ADHD-associated risk for smoking (Schoenfelder et al., 2014).   The authors concluded that, for ADHD patients, "Consistent stimulant treatment for ADHD may reduce the risk of smoking". This finding is especially notable given that, for ADHD youth, cigarette smoking is a gateway drug to more serious addictions (Biederman et al., 2006).

 Yes, ADHD is a serious disorder.  Although most ADHD people will be spared the worst of these outcomes, they must be considered by parents and patients when weighing the pros and cons of treatment options.

November 16, 2023

How to Avoid False Positives and False Negatives when Diagnosing Adult ADHD

How to Avoid False Positives and False Negatives when Diagnosing Adult ADHD?

A recent paper by Margaret Sibley and colleagues addresses a key issue in the diagnosis of adult ADHD. Is it sufficient to only collect data from the patient being diagnosed or are informants useful or, perhaps, essential, for diagnosing ADHD in adults? Dr. Sibley presented a systematic review of twelve studies that prospectively followed ADHD children into adulthood. Each of these studies asked a simple question: What fraction of ADHD youth continued to have ADHD in adulthood. Surprisingly, the estimates of ADHD's persistence ranged from a low of4% to a high of 77%. They found two study features that accounted for much of this wide range. The first was the nature of the informant; did the study rely only on the patient's report, or were other informants consulted. The second was the use of a strict diagnostic threshold of six symptoms. When they limited the analysis to studies that used informants and eliminated the six symptom threshold, the range of estimates was much narrower, 40% to 77%. From studies that computed multiple measures of persistence using different criteria, the authors concluded: "(1) requiring impairment to be present for diagnosis reduced persistence rates; (2) a norm-based symptom threshold led to higher persistence than a strict six-symptom DSM-based symptom count criterion; and (3) informant reports tended to show a higher number of symptoms than self-reports." These data have clear implications for what clinicians can do to avoid false positive and false negative diagnoses when diagnosing adult ADHD. It is reassuring that the self-reports of ADHD patients tend to underestimate the number and severity of ADHD symptoms. This means that your patients are not typically exaggerating their symptoms. Put differently, self-reports will not lead you to over-diagnose adult ADHD. Instead, reliance on self-reports can lead to false-negative diagnoses, i.e., concluding that someone does not have ADHD when, in fact, they do. You can avoid false negatives by doing a thorough assessment, which is facilitated by some tools available at www. ADHD in adults. Command described in CME videos there. If you think a patient might have ADHD but are not certain, it would be helpful to collect data from an informant, i.e., someone who knows the patient well such as a spouse, partner, roommate, or parent. You can collect such data by sending home a rating scale or by having the patient bring an informant to a subsequent visit. Dr. Sibley's paper also shows that you can avoid false-negative diagnoses by using a lower symptom threshold than what is required in the diagnostic manual. The new DSM 5 lowered the symptom threshold for adults from six to five. Can you go lower? Yes, but it is essential to show that these symptoms lead to clear impairments in living. Importantly, this symptom threshold refers to the number of symptoms documented in adulthood, not to the number of symptoms retrospectively reported in childhood. To be diagnosed with ADHD in adulthood, one must document that the patient had at least six impairing symptoms of ADHD before the age of 12.

April 29, 2021

What is Evidenced-Based Medicine?

What is Evidenced-Based Medicine?

With the growth of the Internet, we are flooded with information about attention deficit hyperactivity disorder from many sources, most of which aim to provide useful and compelling "facts" about the disorder.  But, for the cautious reader, separating fact from opinion can be difficult when writers have not spelled out how they have come to decide that the information they present is factual. 

My blog has several guidelines to reassure readers that the information they read about ADHD is up-to-date and dependable. They are as follows:

Nearly all the information presented is based on peer-reviewed publications in the scientific literature about ADHD. "Peer-reviewed" means that other scientists read the article and made suggestions for changes and approved that it was of sufficient quality for publication. I say "nearly all" because in some cases I've used books or other information published by colleagues who have a reputation for high-quality science.

When expressing certainty about putative facts, I am guided by the principles of evidence-based medicine, which recognizes that the degree to which we can be certain about the truth of scientific statements depends on several features of the scientific papers used to justify the statements, such as the number of studies available and the quality of the individual studies. For example, compare these two types of studies.  One study gives drug X to 10 ADHD patients and reported that 7 improved.  Another gave drug Y to 100 patients and a placebo to 100 other patients and used statistics to show that the rate of improvement was significantly greater in the drug-treated group. The second study is much better and much larger, so we should be more confident in its conclusions. The rules of evidence are fairly complex and can be viewed at the Oxford Center for Evidenced Based Medicine (OCEBM;

The evidenced-based approach incorporates two types of information: a) the quality of the evidence and b) the magnitude of the treatment effect. The OCEBM levels of evidence quality are defined as follows (higher numbers are better:

  1. Mechanism-based reasoning.  For example, some data suggest that oxidative stress leads to ADHD, and we know that omega-3 fatty acids reduce oxidative stress. So there is a reasonable mechanism whereby omega-3 therapy might help ADHD people.
  2. Studies of one or a few people without a control group, or studies that compare treated patients to those that were not treated in the past.

Non-randomized, controlled studies.    In these studies, the treatment group is compared to a group that receives a placebo treatment, which is a fake treatment not expected to work.  

  1. Non-randomized means that the comparison might be confounded by having placed different types of patients in the treatment and control groups.
  2. A single randomized trial.  This type of study is not confounded.
  3. Systematic review and meta-analysis of randomized trials. This means that many randomized trials have been completed and someone has combined them to reach a more accurate conclusion.

It is possible to have high-quality evidence proving that a treatment works but the treatment might not work very well. So it is important to consider the magnitude of the treatment effect, also called the "effect size" by statisticians. For ADHD, it is easiest to think about ranking treatments on a ten-point scale. The stimulant medications have a quality rating of 5 and also have the strongest magnitude of effect, about 9 or 10.Omega-3 fatty acid supplementation 'works' with a quality rating of 5, but the score for the magnitude of the effect is only 2, so it doesn't work very well. We have to take into account patient or parent preferences, comorbid conditions, prior response to treatment, and other issues when choosing a treatment for a specific patient, but we can only use an evidence-based approach when deciding which treatments are well-supported as helpful for a disorder.

April 23, 2021

How do Stimulants Modulate the Brain to Improve ADHD Symptoms?

How do Stimulants Modulate the Brain to Improve ADHD Symptoms?

The stimulants methylphenidate and amphetamine are well known for their efficacy in treating symptoms of ADHD in both youth and adults.   Although these medications have been used for several decades, relatively little is known about the mechanisms of action that lead to their therapeutic effect.    

New data about the mechanism comes from a meta-analysis by Katya Rubia and colleagues. They analyzed 14 functional magnetic resonance imaging (fMRI) data sets comprising 212 youth with ADHD.  Each of these data sets assessed the short-term effects of stimulants on fMRI-assessed brain activations. In the fMRI paradigm, ADHD and control participants are asked to do a neurocognitive task while the activity of their brains is being measured. Dr. Rubia and colleagues analyzed data from fMRI assessments of time discrimination, inhibition, and working memory, each of which is known to be deficient in ADHD patients.    

The meta-analysis found that the most consistent brain activations were seen in a region comprising the right inferior frontal cortex(IFC) and insula, even when the analysis was limited to previously medication-naïve patients. The implicated region of the brain is known to mediate cognitive control, time estimation, and attention.  Dr.Rubia also notes that other studies show that the IFC/Insula is needed for updating information and allocating attention to relevant stimuli.  

Another region implicate by the meta-analysis was the right putamen, a region that is rich in dopamine transporters. This finding is consistent with the fact that the dopamine transporter is the main target of stimulant medications.    

What is the potential clinical implication of these findings?  As Dr. Rubia and colleagues note, it is possible that the fMRI anomalies they identified could be used as a biomarker for ADHD or a biomarker to select patients who should respond optimally to stimulant medication. Although fMRI cannot be used as a clinical tool at this time, research of this sort is opening up new horizons for how we understand the etiology of ADHD and the mechanisms whereby medications exert their effects.

April 21, 2021

Is Cognitive Behavior Therapy Effective for Treating Adult ADHD?

Is Cognitive Behavior Therapy Effective for Treating Adult ADHD?

The term "cognitive behavior therapy (CBT)" refers to a type of talk therapy that seeks to change the way patients think about themselves, their disorder, and the world around them in a manner that will help them overcome symptoms and achieve life goals.

Because CBT is typically administered by a psychologist or other mental health professionals, CBT services are not available in primary care. Nonetheless, it is useful for primary care practitioners to know about CBT so that they can refer appropriately as needed. So, what can we say about the efficacy of CBT for treating adults with ADHD?

Based on a meta-analysis by Young and colleagues, we know for certain that the number of published trials of CBT for adult ADHD is small; only nine trials are available. Five of these compared CBT with waiting list controls; three compared CBT with appropriate placebo control groups. In all of these studies, patients in the CBT and control groups were also being treated with ADHD medications.

Thus, they speak to the efficacy of CBT when given as an adjunctive treatment. The meta-analysis examined the waiting list controlled studies and the placebo-controlled studies separately. For both types of study, the effect of CBT in reducing ADHD symptoms was statistically significant, with a standardized mean effect size of 0.4.

This effect size, albeit modest, is large enough to conclude that CBT will be useful for some patients being treated with ADHD medications. Given these results, a reasonable guideline would be to refer adults with ADHD to a CBT therapist if they are being maintained on an ADHD medication, but that medication is not leading to a complete remission of their symptoms and impairments. So listen to your patients. If, while on an appropriately titrated medication regime, they still complain about unresolved symptoms or impairments, you need to take action.  In some cases, changing their dose or shifting to another medication will be useful. If such approaches fail or are not feasible, you should consider referral to a CBT therapist.

April 17, 2021

A Brief History of ADHD

A Brief History of ADHD

I have too often seen on the Internet or media the statement that ADHD is a recent invention of psychiatrists and/or pharmaceutical companies. Such statements ignore the long history of ADHD that my colleague and I reviewed in our "Primer" about ADHD.  

ADHD has a long history. The first ADHD syndrome was described in a German medical textbook by Weikard in 1775. That's not a typo. The ADHD syndrome had been identified before the birth of the USA. Dr.Weikard did not use the term ADD or ADHD, yet he described a syndrome of hyperactivity and inattention that corresponds to what we call ADHD today.  

ADHD-like syndromes were described in Scotland in 1798 and in France in the late 19th century. The first description of an ADHD-like syndrome in a medical journal was by Dr. George Still in 1901 who described what he called a 'defect of moral control' in The Lancet. The discovery that stimulant drugs are effective in treating ADHD occurred in 1937 when Dr. Charles Bradley discovered that Benzedrine (an amphetamine compound) improved the behavior of children diagnosed with behavioral disorders. In subsequent years, several terms were used to describe children with ADHD symptoms. Examples are Kramer-Pollnow syndrome, minimal brain damage, minimal brain dysfunction, and hyperkinetic reaction.  

,It was not until the 1980s that the term Attention Deficit Disorder (ADD) came into widespread use with the publication of the American Psychiatric Association's Diagnostic and Statistical Manual (DSM).   During the ensuing decades, several changes were made to the diagnostic criteria and the term ADD was replaced with ADHD so as not to overemphasize either inattention or hyperactivity when diagnosing the disorder. And, as the graphic below describes, these new and better diagnostic criteria led to many breakthroughs in our understanding of the nature of the disorder and the efficacy of treatments. So, if you think that ADHD is an invention of contemporary society, think again. It has been with us for quite some time.

April 11, 2021

The Goal of ADHD Diagnosis? Safe and Effective Treatment

The Goal of ADHD Diagnosis? Safe and Effective Treatment

The diagnosis of ADHD should only be done by a licensed clinician, and that clinician should have one goal in mind: to plan a safe and effective course of evidence-based treatment. The infographic gives a summary of this diagnostic approach which my colleagues and I prepared for our "Primer" about ADHD,  A key point that parents of ADHD youth and adults with ADHD should keep in mind is that there is only one way to diagnose ADHD.An expert clinician must document the criteria for the disorder as specified by either the Diagnostic and Statistical Manual of the American Psychiatric Association, which is now in its fifth edition (DSM-5), or the World Health Organization's International Classification of Diseases (ICD-10). The two sets of criteria are nearly identical. These criteria are most commonly applied by a clinician asking questions of the parent (for children) and/or patient (for adolescents and adults).For children, information from the teacher can be useful. Some clinicians get this information by having the parent ask the teacher to fill out a rating scale. This information can be very useful if it is available.  When diagnosing adults, it is also useful to collect information from a significant other, which can be a parent for young adults or a spouse for older adults. But when such informants are not available, diagnosing ADHD based on the patient's self-report is valid. As the infographic indicates, any diagnosis of ADHD should also assess for comorbid psychiatric disorders, as these have implications for which ADHD medications will be safe and effective. And because a prior history of cardiovascular disease or seizures frequently contraindicate stimulants. These must also be assessed.

April 9, 2021

ADHD Treatment Decision Tree

ADHD Treatment Decision Tree

If you've ever wondered how experts make treatment recommendations for patients with ADHD, take a look at this ADHD treatment decision tree that my colleagues and I constructed for our "Primer" about ADHD,  

Although a picture is worth a thousand words, keep in mind that this infographic only gives the bare bones of a complex process. That said, it is telling that one of the first questions an expert asks is if the patient has a comorbid condition that is more severe than ADHD. The general rule is to treat the more severe disorder first and after that condition has been stabilized plan a treatment approach for the other condition. Stimulants are typically the first-line treatment due to their greater efficacy compared with non-stimulants.

When considering any medication treatment for ADHD safety is the first concern, which is why medical contraindications to stimulants, such as cardiovascular issues or concerns about substance abuse, must be considered. For very young children (preschoolers) family behavior therapy is typically used before medication. Clinicians also must deal with personal preferences.  Some parents and some adolescents and adults with ADHD simply don't want to take stimulant medications for the disorder. When that happens, clinicians should do their best to educate them about the costs and benefits of stimulant treatment.

If, as is the case for most patients, the doctor takes the stimulant arm of the decision tree, he or she must next decide if methylphenidate or amphetamine is more appropriate. Here there is very little guidance for doctors. Amphetamine compounds are a bit more effective, but can lead to greater side effects.  Genetic studies suggest that a person's genetic background provides some information about who will respond well to methylphenidate, but we are not yet able to make very accurate predictions. After choosing the type of stimulant, the doctor must next consider what duration of action is appropriate for each patient.

There is no simple rule here; the choice will depend upon the specific needs of each patient. Many children benefit from longer-acting medications to get them through school, homework, and late afternoon/evening social activities. Likewise for adults. But many patients prefer shorter-acting medications, especially as these can be used to target specific times of day and can also lower the burden of side effects.  

For patients taking down the non-stimulant arm of the decision tree, duration is not an issue but the patient and doctor must choose from among two classes of medications norepinephrine reuptake inhibitors or alpha-2-agonists. There are not a lot of good data to guide this decision but, again, genetics can be useful in some cases. Regardless of whether the first treatment is a stimulant or a non-stimulant, the patient's response must be closely monitored as there is no guarantee that the first choice of medication will work out well. In some cases, efficacy is low, or adverse events are high. Sometimes this can be fixed by changing the dose, and sometimes a trial of a new medication is indicated.

If you are a parent of a child with ADHD or an adult with ADHD, this trial-and-error approach can be frustrating. But don't lose hope. In the end, most ADHD patients find a dose and a medication that works for them. Last but not least, when medication leads to a partial response, even after adjusting doses and trying different medication types, doctors should consider referring the patient for a non-pharmacologic ADHD treatment.

You can read details about these in my other blogs, but here the main point is to find an evidence-based treatment. For children, the biggest evidence base is for behavioral family therapy. For adults, cognitive behavior therapy (CBT) is the best choice.  Except for preschoolers, the experts I worked with on this infographic did not recommend these therapies before medication treatment. The reason is that the medications are much more effective, and many non-pharmacologic treatments (such as CBT) have no data indicating they work well in the absence of medication.

April 3, 2021

What is Sluggish Cognitive Tempo and is it Relevant to ADHD?

What is Sluggish Cognitive Tempo and is it Relevant to ADHD?

Over the past few decades, a consensus has emerged among psychopathologists that some patients exhibit a well-defined syndrome referred to as sluggish cognitive tempo or SCT.

There are no diagnostic criteria for SCT because it has not yet been accepted as a separate disorder by the American Psychiatric Association. People with SCT are slow-moving, indolent, and mentally muddled. They often appear to be lost in thoughts, daydreaming, drowsy or listless. In reviewing these symptoms and the literature, Barkley suggested that SCT be referred to as Concentration Deficit Disorder (CDD). This term is less pejorative, but is not yet commonly used.

Becker and colleagues recently evaluated the internal and external validity of SCT via a meta-analysis of 73 studies. Internal validity addresses the consistency of SCT symptoms as a measure of an underlying construct. Based on factor analytic studies using more than 19,000 participants, the authors concluded that the items purported to measure SCT are sufficiently correlated with one another to justify the idea that they measure the same underlying construct.

Further support for internal validity was found in studies reporting high test-retest and interrater reliability. As regards ADHD, the authors found that SCT correlated significantly with both inattentive (r = 0.72) and hyperactive-impulsive (r = 0.46) symptoms in adults. The greater correlation with inattentive symptoms makes sense given the nature of SCT symptoms. So these data confirm two key points about SCT: 1) it is associated with ADHD symptoms, and 2) it is a meaningful construct in its own right. Very little is known about the implications of SCT for the treatment of ADHD.  

In a naturalistic study of 88 children and adolescents with ADHD, Ludwig and colleagues examined the effect of SCT on the response of ADHD symptoms to methylphenidate. They found no significant differences in treatment response between subjects with and without SCT. McBurnett and colleagues tested the effects of atomoxetine on SCT in children with ADHD and dyslexia (ADHD+D) or dyslexia only. Atomoxetine treatment led to significant reductions in both ADHD symptoms and SCT outcomes.

Because controlling for changes in ADHD symptoms did not predict changes in SCT outcomes, the authors concluded that change in SCT in response to atomoxetine is mostly independent of change in ADHD. Although these data are preliminary and in need of replication, they do provide some guidance for clinicians dealing with ADHD patients who also have SCT.

March 26, 2021