April 24, 2024

Large Six-region Meta-analysis Finds No Association Between ADHD Medications and Cardiovascular Risk

Are attention-deficit/hyperactivity disorder (ADHD) medications associated with risk of cardiovascular disease (CVD)?

An international study team has just explored this question with a meta-analysis of nineteen studies with a total of almost four million participants of all ages. It included 3,931,532 participants from six countries or regions: United States, South Korea, Canada, Denmark, Spain, and Hong Kong. 

Overall, using the entire data set, it found no significant association between any ADHD medication use and any cardiovascular event. 

The same held true when breaking this down by children and adolescents (twelve studies with over 1.7 million participants), young and middle-aged adults (seven studies with over 850,000 participants), and older adults (six studies with over a quarter million participants).

The team then compared the data for stimulant medications with data for non-stimulant medications. A meta-analysis of 17 studies with over 3.8 million participants found no significant association between stimulant medications and cardiovascular risk. Similarly, a meta-analysis of three studies with over 670,000 participants found no significant association between non-stimulant medications and cardiovascular risk.

Distinguishing between types of cardiovascular risk made no difference. For instance, a meta-analysis of nine studies with over 900,000 participants found no effect of stimulant medications on risk of myocardial infarction (heart attack), and a meta-analysis of six studies, also with over 900,000 participants, found no effect of stimulant medications on risk of cerebrovascular disease, including stroke, brain aneurysm, brain bleed, and carotid artery disease. A meta-analysis of eight studies with over 1.1 million participants did find an increase in theoccurrence of cardiac arrest and tachyarrhythmias (racing heart rate accompanied by arrhythmias), but it was not statistically significant.

A meta-analysis of eleven studies with over 3.1 million persons with no prior history of cardiovascular disease found absolutely no effect of ADHD medications on subsequent risk for any cardiovascular event. Another meta-analysis, of eight studies encompassing over 1.8 million individuals with a prior history of cardiovascular disease, reported a higher rate of subsequent occurrence, but it was not considered statistically significant.

The team concluded, “Overall, our meta-analysis provides reassuring data on the putative cardiovascular risk with ADHD medications.” An international team of researchers recently investigated whether medications for attention-deficit/hyperactivity disorder (ADHD) are linked to an increased risk of cardiovascular disease (CVD). They conducted a comprehensive review, known as a meta-analysis, which included 19 studies with nearly four million participants from six countries or regions: the United States, South Korea, Canada, Denmark, Spain, and Hong Kong.

The findings from the entire data set showed no significant link between the use of any ADHD medications and the occurrence of cardiovascular events. This lack of association was consistent across all age groups: children and adolescents (12 studies with over 1.7 million participants), young and middle-aged adults (7 studies with over 850,000 participants), and older adults (6 studies with over 250,000 participants).

The researchers also compared the effects of stimulant medications against non-stimulant medications on cardiovascular risk. Both categories showed no significant risks in a meta-analysis of 17 studies with more than 3.8 million participants for stimulants, and three studies with over 670,000 participants for non-stimulants.

Further analysis differentiated between types of cardiovascular risks, such as myocardial infarction (heart attack) and cerebrovascular diseases (like stroke, brain aneurysm, and carotid artery disease). Again, stimulant medications showed no significant impact on these conditions in studies involving over 900,000 participants each. However, a review of eight studies with over 1.1 million participants suggested a slight increase in incidents of cardiac arrest and tachyarrhythmias (a racing heart rate with irregular rhythms), but these findings were not statistically significant.

Additionally, an analysis of 11 studies involving more than 3.1 million people without a prior history of cardiovascular disease found no effect of ADHD medications on the risk of developing cardiovascular events. Likewise, an analysis of eight studies with over 1.8 million individuals who had a history of cardiovascular disease showed a higher occurrence rate of events, but this increase was also not statistically significant.

The conclusion of the research team was clear: the data is reassuring and does not suggest a substantial cardiovascular risk associated with ADHD medications. Keep in  mind that this reflects current standards of care.  Most guidelines call for monitoring of pulse and blood pressure during treatment so that adverse cardiovascular outcomes can be avoided.

Le Zhang, Honghui Yao, Lin Li, Ebba Du Rietz, Pontus Andell, Miguel Garcia-Argibay, Brian M. D’Onofrio, Samuele Cortese, Henrik Larsson, Zheng Chang, “Risk of Cardiovascular Diseases Associated With Medications Used in Attention-Deficit/Hyperactivity Disorder: A Systematic Review and Meta-analysis,” JAMA Network Open (2022) 5(11), e2243597, https://doi.org/10.1001/jamanetworkopen.2022.43597.

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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

ADHD medication and risk of suicide

ADHD medication and risk of suicide

A Chinese research team performed two types of meta-analyses to compare the risk of suicide for ADHD patients taking ADHD medication as opposed to those not taking medication.

The first type of meta-analysis combined six large population studies with a total of over 4.7 million participants. These were located on three continents - Europe, Asia, and North America - and more specifically Sweden, England, Taiwan, and the United States.

The risk of suicide among those taking medication was found to be about a quarter less than for unmediated individuals, though the results were barely significant at the 95 percent confidence level (p = 0.49, just a sliver below the p = 0.5 cutoff point). There were no significant differences between males and females, except that looking only at males or females reduced sample size and made results non-significant.

Differentiating between patients receiving stimulant and non-stimulant medications produced divergent outcomes. A meta-analysis of four population studies covering almost 900,000 individuals found stimulant medications to be associated with a 28 percent reduced risk of suicide. On the other hand, a meta-analysis of three studies with over 62,000 individuals found no significant difference in suicide risk for non-stimulant medications. The benefit, therefore, seems limited to stimulant medication.

The second type of meta-analysis combined three within-individual studies with over 3.9 million persons in the United States, China, and Sweden. The risk of suicide among those taking medication was found to be almost a third less than for unmediated individuals, though the results were again barely significant at the 95 percent confidence level (p =0.49, just a sliver below the p = 0.5 cutoff point). Once again, there were no significant differences between males and females, except that looking only at males or females reduced the sample size and made results non-significant.

Differentiating between patients receiving stimulant and non-stimulant medications once again produced divergent outcomes. Meta-analysis of the same three studies found a 25 percent reduced risk of suicide among those taking stimulant medications. But as in the population studies, a meta-analysis of two studies with over 3.9 million persons found no reduction in risk among those taking non-stimulant medications.

A further meta-analysis of two studies with 3.9 million persons found no reduction in suicide risk among persons taking ADHD medications for 90 days or less, "revealing the importance of duration and adherence to medication in all individuals prescribed stimulants for ADHD."

The authors concluded, "exposure to non-stimulants is not associated with a higher risk of suicide attempts. However, a lower risk of suicide attempts was observed for stimulant drugs. However, the results must be interpreted with caution due to the evidence of heterogeneity ..."

December 13, 2021

News Tuesday: Fidgeting and ADHD

A recent study delved into the connection between fidgeting and cognitive performance in adults with Attention-Deficit/Hyperactivity Disorder. Recognizing that hyperactivity often manifests as fidgeting, the researchers sought to understand its role in attention and performance during cognitively demanding tasks. They designed a framework to quantify meaningful fidgeting variables using actigraphy devices.

(Note: Actigraphy is a non-invasive method of monitoring human rest/activity cycles. It involves the use of a small, wearable device called an actigraph or actimetry sensor, typically worn on the wrist, similar to a watch. The actigraph records movement data over extended periods, often days to weeks, to track sleep patterns, activity levels, and circadian rhythms. In this study, actigraphy devices were used to measure fidgeting by recording the participants' movements continuously during the cognitive task. This data provided objective, quantitative measures of fidgeting, allowing the researchers to analyze its relationship with attention and task performance.)

The study involved 70 adult participants aged 18-50, all diagnosed with ADHD. Participants underwent a thorough screening process, including clinical interviews and ADHD symptom ratings. The analysis revealed that fidgeting increased during correct trials, particularly in participants with consistent reaction times, suggesting that fidgeting helps sustain attention. Interestingly, fidgeting patterns varied between early and later trials, further highlighting its role in maintaining focus over time.

Additionally, a correlation analysis validated the relevance of the newly defined fidget variables with ADHD symptom severity. This finding suggests that fidgeting may act as a compensatory mechanism for individuals with ADHD, aiding in their ability to maintain attention during tasks requiring cognitive control.

This study provides valuable insights into the role of fidgeting in adults with ADHD, suggesting that it may help sustain attention during challenging cognitive tasks. By introducing and validating new fidget variables, the researchers hope to standardize future quantitative research in this area. Understanding the compensatory role of fidgeting can lead to better management strategies for ADHD, emphasizing the potential benefits of movement for maintaining focus.

July 16, 2024

Identifying Autistic-Like Symptoms in Children with ADHD

NEWS TUESDAY: Identifying Autistic-Like Symptoms in Children with ADHD

A recent study investigated the presence of autistic-like symptoms in children diagnosed with Attention Deficit/Hyperactivity Disorder (ADHD). Given the overlapping social difficulties in both ADHD and Autism Spectrum Disorder (ASD), distinguishing between the two disorders can be challenging. This study aims to pinpoint specific patterns of autistic symptoms in children with ADHD, comparing them to those with ASD using the Autism Diagnostic Observation Schedule, 2nd edition (ADOS-2).

The research involved 43 school-age children divided into two groups:

  • ADHD Group (25 children): Initially referred for ASD symptoms but later diagnosed with ADHD.
  • ASD Group (18 children): Children diagnosed with ASD.

Researchers used ADOS-2 to evaluate differences in communication deficits, social interaction challenges, and repetitive behaviors between the two groups. The study also compared IQ, age, ADOS-2 domain scores, and externalizing/internalizing problems.

Key Findings:

  • Significant differences were found between the ADHD and ASD groups in ADOS-2 domain scores, including Social Affect, Restricted and Repetitive Behavior, and Total Score.
  • On an individual item level, children with ADHD displayed similar atypical behaviors as those with ASD in social-communication areas such as "Pointing" and "Gestures".
  • Both groups showed comparable frequencies in behaviors like "Stereotyped/idiosyncratic words or phrases", "Mannerisms", and "Repetitive interests and behaviors".

The study highlights the importance of identifying transdiagnostic domains that overlap between ADHD and ASD. The transdiagnostic domain refers to a set of symptoms or behaviors that are common across multiple diagnostic categories rather than being specific to just one. Identifying these domains in mental health practice and in psychological research is crucial to understanding, properly diagnosing, and treating conditions with overlapping features. This understanding could pave the way for tailored treatments addressing the specific needs of children with ADHD, particularly those exhibiting autistic-like symptoms.

July 9, 2024

Non-stimulant Medications for Adults with ADHD: An Overview

NEW STUDY: Non-stimulant Medications for Adults with ADHD: An Overview

Attention-Deficit/Hyperactivity Disorder (ADHD) in adults is commonly treated with stimulant medications such as methylphenidate and amphetamines. However, not all patients respond well to these stimulants or tolerate them effectively. For such cases, non-stimulant medications provide an alternative treatment approach.

Recent research by Brancati et al. reviews the efficacy and safety of non-stimulant medications for adult ADHD. Atomoxetine, a well-studied non-stimulant, has shown significant effectiveness in treating ADHD symptoms in adults. The review highlights the importance of considering dosage, treatment duration, safety, and the presence of psychiatric comorbidities when prescribing atomoxetine.

Additionally, certain antidepressants, including tricyclic compounds, bupropion, and viloxazine, which possess noradrenergic or dopaminergic properties, have demonstrated efficacy in managing adult ADHD. Antihypertensive medications, especially guanfacine, have also been found effective. Other medications like memantine, metadoxine, and mood stabilizers show promise, whereas treatments like galantamine, antipsychotics, and cannabinoids have not yielded positive results.

The expert opinion section of the review emphasizes that while clinical guidelines primarily recommend atomoxetine as a second-line treatment, several other non-stimulant options can be utilized to tailor treatments based on individual patient needs and comorbid conditions. Despite these advancements, the authors call for further research to develop and refine more personalized treatment strategies for adults with ADHD.

This review underscores the growing landscape of non-stimulant treatment options, offering hope for more personalized and effective management of ADHD in adults.

June 25, 2024