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May 9, 2024

Population Study Finds Reductions in Crime Rates Among Persons with ADHD Receiving Pharmacological Treatment

Population Study Finds Reductions in Violent and Public Order Crime Rates Among Persons with ADHD Receiving Pharmacological Treatment

Norway has a single-payer health insurance system that covers virtually the entire population and is linked to a series of national registries tracking all sorts of data including criminal records.

Using this data, a study team identified all 5,624 persons aged 10 to 18 diagnosed with ADHD between 2009 and 2011. It tracked their use of ADHD medication, and subsequent criminal charges. 

Filled prescriptions were primarily for stimulant methylphenidate (90%) and the nonstimulant atomoxetine (9.5%). They tracked the cumulative number of daily defined doses (DDD) filled for any ADHD prescriptions following ADHD diagnosis. 

They also compared this group with a general population sample of persons aged 10 to 18 without contact with mental health services, matched on age, sex, and geography.

They adjusted for the following confounders: age, sex, year of contact with clinic, psychiatric comorbidity at time of diagnosis, country of birth, charges before ADHD diagnosis, parents’ marital status, parent’s highest education when the child was 6 years, and parent’s labor income when the child was 6 years. 

They further adjusted for municipality-level population size and high school dropout rates, and the following aggregated measures from the random sample of the general population: municipality-level labor income of parents and clinic-level percent of youth crime, youth immigrants, mothers’ marriage rate, and parents’ education level.

Comparing persons with ADHD to the matched general population over eight years follow-up, those with ADHD had considerably higher rates of criminal charges:

  • 2.7 times more likely to be charged with any crime.
  • 6 times more likely to be charged with a violent crime.
  • 7 times more likely to be charged with a sexual offense (though only among males)
  • 4 times more likely to be charged with property crimes.

Next the team examined outcomes of pharmaceutical treatment.

Comparing persons with ADHD undergoing pharmacological treatment with those not receiving such treatment, those undergoing treatment had lower rates of certain criminal charges. At two years follow-up, those treated had 7.3% less violence-related charges. This corresponds to a number needed to treat (NNT) estimate of 14, indicating that on average treating 14 patients for two years avoids one violence-related criminal charge. Pharmacological treatment reduces public-order charges by at four years follow-up by 15.4% (NNT = 7), and any crime at three years follow-up by 18.5% (NNT = 5).

The authors noted, “Violence and public-order crimes are often caused by reactive-impulsive behavior which is more common in ADHD,” and concluded, “this is the first study to demonstrate causal effects of pharmacological treatment of ADHD on some types of crimes in a population-based natural experiment. Pharmacological treatment of ADHD reduced crime related to impulsive-reactive behavior in patients with ADHD on the margin of treatment, while no effects were found in crimes requiring criminal intent, conspiracy, and planning.”

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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
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Nationwide population study suggests ADHD medication may reduce child abuse

Nationwide Population Study Suggests ADHD Medication May Reduce Child Abuse

Child abuse includes any of the following inflicted on a minor under 18 years old: physical or emotional harm, sexual abuse, or neglect.

Child abuse includes any of the following inflicted on a minor under 18 years old: physical or emotional harm, sexual abuse, or neglect.

It is known to be associated with environmental factors such as poverty, parents or neighbors with a history of violence, and gender inequality.

Chronic mental disorders in minors are also associated with child abuse. To what extent, if any, might that be true of ADHD?

Taiwan has a single-payer national health insurance system that covers more than 99.6% of all residents, enabling nationwide population studies.

A local research team used data from almost two million Taiwanese in their country’s National Health Insurance Research Database (NHIRD) spanning 15 years (2000-2015) to carry out a matched-cohort study. 

All diagnoses of ADHD were made by board-certified specialists such as psychiatrists, pediatricians, neurologists, or physiatrists with a specialty in child and adolescent development.

3,540 children and adolescents between 6 and 18 years old with a diagnosis of ADHD were matched on a one-to-three basis with 10,620 peers from the NHIRD without an ADHD diagnosis.

The team adjusted for age, gender, location of residence (Northern, Central, Southern, and Eastern Taiwan), urbanization level of residence, level of hospitals as medical centers, and monthly insured premium. They further adjusted for comorbid conditions: intellectual disability, autistic disorder/pervasive developmental disorder, conduct disorder (CD)/oppositional defiant disorder (ODD), other developmental disorders, childhood emotional disorder, Tourette syndrome/tics disorders, and involuntary urination and defecation.

Overall, children and adolescents with an ADHD diagnosis were 1.8 times as likely to be abused as those without an ADHD diagnosis.

Unmedicated children and adolescents with an ADHD diagnosis were three times more likely to be abused. ADHD medication cut that risk in half.

That held true whether the medication used was methylphenidate or atomoxetine. Methylphenidate appeared to be slightly more effective than atomoxetine, and the combination of methylphenidate and atomoxetine slightly more effective yet, but these differences were not statistically significant.

The team concluded, “The results support that pharmacotherapy may attenuate the risk of child abuse in ADHD patients.”

March 5, 2024
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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
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Nationwide population study finds no harm from in utero exposure to ADHD medication

Nationwide Population Study Finds No Harm from In Utero Exposure to ADHD Medication

Now that ADHD pharmaceuticals are among the most widely prescribed medications during pregnancy, we need to be aware of any long-term harms to offspring from in utero exposure.

Now that ADHD pharmaceuticals are among the most widely prescribed medications during pregnancy, we need to be aware of any long-term harms to offspring from in-utero exposure.

Denmark has a single-payer public health care system that encompasses virtually its entire population. Combined with national registers that track demographic as well as health data for the whole population, this makes it easy to do population-wide studies.

Availing itself of these registers, an international study team looked at all 1,068,073 single births from 1998 to 2015. It then followed all these individuals through the end of 2018, or until any developmental diagnosis, death, or emigration, whichever came first.

The team compared children of mothers who continued ADHD medication (methylphenidate, amphetamine, dexamphetamine, lisdexamphetamine, modafinil, atomoxetine, clonidine) during pregnancy with children of mothers who discontinued ADHD medication before pregnancy. There were 898 of the former and 1,270 of the latter in the cohort.

To reduce the influence of potential confounding variables, the team adjusted for maternal age, parity, maternal psychiatric history, in- or outpatient admission to psychiatric ward within two years prior to pregnancy and until delivery, use of other psychotropic medications during pregnancy, number of hospitalizations during pregnancy not related to psychiatry, smoking during pregnancy, living alone, education, birthyear, and psychiatric history of the father. 

Children exposed in utero to ADHD medication were found to be at no greater risk of any developmental impairment.

The timing of the exposure by trimester of pregnancy made no difference. Neither did the duration of exposure.

Neither children exposed to stimulant medications (methylphenidate, amphetamine, dexamphetamine, lisdexamphetamine, modafinil) nor to non-stimulants (atomoxetine, clonidine) were at greater risk of any developmental impairment

Focusing more narrowly on specific impairments, children exposed in utero to ADHD medication were no more likely to be autistic. They were more likely to have ADHD, but the association did not reach statistical significance.

Children exposed in utero to ADHD medication were also no more likely to develop hearing or cerebral vision impairment or febrile seizures or a growth impairment. Surprisingly, they were 40% less likely to become epileptic, the only statistically significant association found in the study.

The authors concluded, “Our results are important because stimulant medications are critical for many adults, including women of childbearing age, to perform their essential functions at work, home, and school. Pregnant women who depend on stimulants for daily functioning must weigh the potential of exposing their fetus to unknown developmental risks against potential medical, financial, and other consequences to both mother and child that are associated with exacerbation of ADHD symptoms when stopping the medication, such as inability to maintain employment and unsafe driving. The present study provides reassurance that several essential categories of child outcomes that could reasonably be suspected to be affected by stimulants, including body growth, neurodevelopment, and seizure risk, do not differ based on antenatal stimulant exposure. Future studies would benefit from larger sample sizes making it possible to conduct stratified analyses on ADHD medication type.”

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Study of U.S. 12th grade public and private school students finds no link between stimulant use for ADHD and subsequent cocaine or methamphetamine use

Large Scale Study of U.S. High Schoolers Finds No Link Between Stimulant Use for ADHD and Subsequent Cocaine or Methamphetamine Use

Monitoring the Future is a multicohort U.S. national longitudinal study of adolescents followed up into young adulthood.

Monitoring the Future is a multicohort U.S. national longitudinal study of adolescents followed up into young adulthood. 

The U.S. research team used data from this study to follow 5,034 twelfth graders over a period of six years, until they were 23 and 24 years of age.

Prescription stimulant misuse was assessed at baseline and each follow-up survey year by asking how often they used prescription stimulants without a physician’s orders. They were similarly asked about cocaine and methamphetamine use.

The study team adjusted for the following confounding variables: sex, race and ethnicity, parents’ level of education, urbanicity, U.S. region, cohort year, grade point average during high school, past-30-day cigarette use (at 18 years of age), past-2-week binge drinking (at 18), past-year marijuana use (at 18), past-year prescription opioid misuse (at 18), past-year prescription stimulant misuse (at 18), lifetime cocaine use (at 18), lifetime methamphetamine use (at 18), lifetime use of nonstimulant therapy for ADHD (at 18), and discontinued use of stimulant therapy for ADHD (at 18).

With these adjustments, they found that stimulant use for ADHD was in no way associated with subsequent cocaine use. In fact, it was associated with lesser odds of subsequent cocaine use, though the association was not statistically significant.

Likewise, they reported that stimulant use for ADHD was in no way associated with subsequent methamphetamine use.

On the other hand, those who used prescription stimulants without a physician’s orders were 2.6 times more likely to subsequently use either cocaine or methamphetamine.

The team concluded, “In this multicohort study of adolescents exposed to prescription stimulants, adolescents who used stimulant therapy for ADHD did not differ from population controls in initiation of illicit stimulant (cocaine or methamphetamine) use, which suggested a potential protective effect, given evidence of elevated illicit stimulant use among those with ADHD. In contrast, monitoring adolescents for PSM is warranted because this behavior offered a strong signal for transitioning to later cocaine or methamphetamine initiation and use during young adulthood.”

February 15, 2024
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Nationwide study of U.S. high schools finds link between percentage of school body on prescription ADHD stimulant medication and the rate of nonmedical use by schoolmates

Nationwide Study of U.S. High Schools Finds Link Between Percentage of Students Prescribed Stimulant Medication and Rate of Nonmedical Use by Schoolmates

Noting that “little is known about whether school-level stimulant therapy for ADHD is associated with NUPS [nonmedical use of prescription stimulants] among US secondary school students,” a team of American researchers searched for answers in a nationally representative sample of 3,284 U.S. secondary schools with well over 150,000 high school students.

Noting that “little is known about whether school-level stimulant therapy for ADHD is associated with NUPS [nonmedical use of prescription stimulants] among US secondary school students,” a team of American researchers searched for answers in a nationally representative sample of 3,284 U.S. secondary schools with well over 150,000 high school students.

“Previous studies,” the authors continued, “have largely neglected school-level factors associated with NUPS among US secondary school students, including school size, school geographical location, school-level racial composition, school-level rates of substance use (eg, binge drinking), and school-level stimulant therapy for ADHD.”

In surveys, students were asked if they had ever taken stimulant medications for ADHD under a physician’s or health professional’s supervision, with three possible answers: no, yes but only in the past, and yes, currently. Responses for use in the past, and separately for current use, were combined and aggregated to the school level to reflect the percentage of the study body who used prescription stimulants for ADHD. 

The surveys explored NUPS by asking, “On how many occasions (if any) have you taken amphetamines or other prescription stimulant drugs on your own—that is, without a doctor telling you to take them... in your lifetime?...during the last 12 months?...during the last 30 days?” 

The study team controlled for sex, race and ethnicity, parental education, GPA, binge drinking, cigarette smoking, cannabis use, cohort year, school type, grade level, urbanicity, school size, US Census region, % of student body with low grades, % female, % with at least one parent with a college degree, % White, % binge drinking during past 2 weeks, % cigarette smoking in past 30 days, and % cannabis use during the past 30 days. The analysis also included individual-level medical use of stimulant therapy for ADHD history to estimate individual-level past-year NUPS. Finally, it included both individual-level and school-level risk factors to assess individual-level past-year NUPS.

With all these adjustments, at the individual level, both high school students presently on prescribed stimulant therapy for ADHD and those who had previously been on such prescribed therapy were more than twice as likely to engage in past-year NUPS as those who were never on prescribed stimulant medication.

Turning to the school level, in schools where 12% or more of students were on prescribed stimulant therapy for ADHD, students in general were 36% more likely to engage in past-year NUPS than in schools where none of the students were on prescribed stimulant therapy for ADHD.

This is not surprising, as it confirms that students who use prescription drugs for nonmedical often get their supply from fellow students who are prescribed those drugs.

While at the individual level, binge drinking, cigarette smoking, and cannabis use were strong predictors of NUPS, at the whole-school level they had no significant effect. A poor grade point average mildly increased risk in the individual, but high percentages of students with low grades had no effect on peer NUPS. Race and ethnicity made a difference at the individual level (NUPS significantly more likely among White students than Blacks and Hispanics), but made no difference at the school level.

The team concluded, “These findings suggest that school-level stimulant therapy for ADHD and other school-level risk factors were significantly associated with NUPS and should be accounted for in risk-reduction strategies and prevention efforts.”

February 21, 2024
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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 www.ADHDevidence.org

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 www.expertscape.com.  Or go to www.pubmed.gov 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
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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
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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
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Meta-analysis finds improvements in executive functioning in children and adolescents from non-pharmacological treatments, but with methodological shortcomings

Meta-analysis Finds Improvements in Executive Functioning From Some Non-Pharmacological ADHD Treatments

ADHD is associated with impaired executive functioning. Executive functioning is a set of mental skills that include working memory, flexible thinking, and self-control. These are skills we use every day to learn, work, and manage daily life. Trouble with executive function can make it hard to focus, follow directions, and handle emotions.

ADHD is associated with impaired executive functioning. Executive functions are a set of mental skills that include working memory, flexible thinking, and self-control. These are skills we use every day to learn, work, and manage daily life. Trouble with executive function can make it hard to focus, follow directions, and handle emotions. 

A Chinese study team searched for studies on non-pharmacological treatments of children and adolescents with ADHD aged 5 to 18 years intended to improve their executive functioning. 

An initial methodological weakness was the decision to combine studies using formal ADHD diagnoses based on professional psychiatric manuals (DSM 3/4/5 and ICD 10/11) and studies relying on other methods such as parent reports.

This lack of rigor in identifying ADHD is surprising given that the team used studies that directly measured executive functioning through neurocognitive tasks, excluding those that relied on parent- or teacher-reported questionnaires. 

67 studies involving 74 training interventions met the criteria. Meta-analysis of all these studies, encompassing a total of 3,101 participants, suggested medium-to-large effect size improvements in executive functioning. There was evidence of publication bias, but trim-and-fill adjustment increased the estimated effect size to large.

Nevertheless, there were further methodological shortcomings:

  • The meta-analysis mixed studies of substantially different interventions: cognitive training, executive function-specific curriculum, game-based training, neurofeedback, mindfulness, and physical exercise.
  • There was tremendous variation (heterogeneity) between study outcomes. Such inconsistency casts doubt on the outcome unless subgroup analysis can explain it. 

In this case, subgroup analysis mostly failed to explain the heterogeneity, with a single exception. Meta-analysis of the 16 studies with 744 participants that explored executive function-specific curriculum found small-to-medium effect size improvements, with no heterogeneity. 

Unfortunately, the team did not perform a separate publication bias analysis on this subgroup, just as it failed to do so on any of the other subgroups.

By far the strongest evidence of benefit came from meta-analysis of the 17 studies with 558 participants evaluating physical exercise. Here the outcome pointed to very large effect size improvements in executive functioning. Yet once again, heterogeneity was extremely high. Breaking this down further between aerobic exercise and cognitively engaged physical exercise made no difference. Both types had the same very high effect size, with very wide heterogeneity. Again, there was no separate evaluation of publication bias on this group.

Meta-analyses of thirteen studies of neurofeedback combining 444 participants, and fifteen studies of cognitive training encompassing 727 participants, both pointed to just-short-of-large effect size improvements in executive function. Meta-analysis of twelve studies of game-based training with 598 participants indicated medium effect size gains. But again, in all three subgroups there was great variation between studies, and no analysis of publication bias.

While these meta-analyses are suggestive of efficacy, especially for physical exercise interventions, their methodological shortcomings mean we will have to await more rigorous meta-analyses to draw any more settled conclusions. Moreover, these meta-analyses did not evaluate the adequacy of the control groups used in the trials, which is a big shortcoming given prior work showing that the effect of non-pharmacologic treatments are very weak or non-existent when adequate controls are used.

March 13, 2024
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