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 the occurrence 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.

Conclusion:

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

Exploring the Impact of ADHD Treatment on Empathy and Narcissism

A recent study published in Alpha Psychiatry sheds light on the connection between ADHD, empathy, and narcissistic traits. Researchers aimed to evaluate how pharmacological treatments—specifically psychostimulants—affect empathy deficits and pathological narcissism in adults with ADHD. These findings could have important implications for enhancing treatment outcomes and improving social functioning.

Study Overview
The study involved 75 adult ADHD patients who were treated with either methylphenidate or atomoxetine. Researchers assessed levels of narcissistic traits and empathy using validated tools such as the Pathological Narcissism Inventory (PNI) and the Empathy Quotient (EQ). Measurements were taken before treatment and after three months of therapy.

Key Findings

  • Narcissistic Traits: Patients showed a significant reduction in grandiosity and vulnerability scores, with total PNI scores decreasing after treatment.
  • Empathy Levels: Empathy improved significantly, as reflected by higher post-treatment EQ scores.
  • Overall Impact: These changes suggest that psychostimulant treatment positively influences brain circuits related to empathy and narcissistic tendencies, potentially leading to better interpersonal relationships.

Why It Matters
Adults with ADHD often struggle with social interactions, partly due to empathy deficits and personality traits like narcissism. By addressing these challenges through psychostimulant treatment, patients may experience better social and emotional well-being. This study underscores the importance of viewing ADHD treatment as not just a way to manage symptoms but also a means to improve overall quality of life.Takeaway
Effective ADHD treatment goes beyond managing attention and hyperactivity. By improving empathy and reducing narcissistic traits, psychostimulants can foster healthier relationships and enhance social functioning. This research highlights the need for comprehensive care that considers the broader psychological and interpersonal effects of ADHD.

February 4, 2025

Meta-analysis Suggests Music Training May Be a Useful Tool for Inhibition Control

According to Fosco et al. (2019), “Inhibitory control has long been considered a central neurocognitive process in ADHD, with ADHD groups typically showing medium-sized impairments relative to their typically-developing peers on common inhibition paradigms.” 

Learning to play a musical instrument requires effective coordination of physical movements and sound signals to produce music. Musical training involves repetitive practice, perfecting connections between perceptions, muscular actions, and cognition. 

Noting that listening to music activates the brain’s reward circuits in both children and adults, that “Being internally motivated during learning experiences increases learning capacity and efficiency, and this greater engagement is reflected in increased electrical brain activity following musical training,” and that “Training music in a social environment increases positive feelings of bonding through shared emotions and group synchrony,” a Montreal-based research team carried out a systematic review and meta-analysis of the peer-reviewed medical literature from 1980 to 2023 to learn what effect music training might have on inhibition control. 

Outcomes:

The team found eight randomized controlled trials (RCTs) and 14 other longitudinal studies that met search criteria, including: 

  • Music training was with neurotypical children and adolescents 
  • The experimental group was trained using music alone 
  • Studies were longitudinal, with either active or passive controls 
  • Studies included a performance-based inhibition control measure as an outcome 

Meta-analysis of all 22 longitudinal studies with a combined total of 1,734 participants yielded a small-to-medium effect size improvement in inhibitory control. Variation (heterogeneity) in outcomes between individual studies was small, and there was no sign of publication bias. Restricting the analysis to the eight RCTs with a combined total of 641 participants, however, yielded a medium-to-large effect size improvement, with negligible heterogeneity, meaning the outcome was consistent across RCTs. 

The Take-Away: The team concluded, “Music training plays a privileged role compared to other activities (sports, visual arts, drama) in improving children’s executive functioning, with a particular effect on inhibition control.”   I cannot, however, recommend this as a therapy for ADHD until RCTs show it reduces symptoms of ADHD and/or real world impairments associated with the disorder.

February 3, 2025

Population Study Finds No ADHD- or ASD- Related Benefits From Eating Organic Food During Pregnancy

Norwegian Nationwide Population Study Finds No ADHD- or ASD- Related Benefits From Eating Organic Food During Pregnancy

Background:

Organic farming aims to protect biodiversity, promote animal welfare, and avoid using pesticides and fertilizers made from petrochemicals. Some pesticides are designed to target insects’ nervous systems but can also affect brain development and health in larger animals, including humans.

Many people believe organic food is healthier than conventionally produced food, which might be true for certain foods and health factors. But does eating organic food during pregnancy impact the chances of a child developing ADHD or autism spectrum disorder (ASD)?

In Norway, researchers can use detailed national health records to study these connections on a population-wide level, thanks to the country’s single-payer healthcare system and national registries.

Method:

The Norwegian Mother, Father, and Child Cohort Study (MoBa) invites parents to participate voluntarily and has a 41% participation rate. The study includes:

  • 114,500 children
  • 95,200 mothers
  • 75,200 fathers

For this research, a team tracked 40,707 mother-child pairs from children born between 2002 and 2009. They used questionnaires to measure how much organic food mothers consumed during pregnancy. ADHD and ASD symptoms in children were assessed using validated rating scales.

The final analysis included:

  • 40,586 pairs for ADHD symptoms
  • 40,117 pairs for ASD symptoms

The researchers adjusted for factors like maternal age, education, previous pregnancies, BMI before pregnancy, smoking and alcohol use during pregnancy, birth year and season, and the child’s sex.

Key Findings:
  • There was a weak connection between higher organic food consumption and fewer ADHD symptoms in children. However, this link disappeared when maternal ADHD symptoms were considered (31,411 pairs) or when the analysis was limited to siblings (5,534 pairs).
  • Similarly, weak associations between organic food and fewer ASD symptoms disappeared when focusing on siblings (4,367 pairs).
Conclusion:

The researchers concluded that eating organic food during pregnancy has no meaningful effect on the likelihood of a child developing ADHD or ASD. They stated, “The results do not indicate any clinically significant protective or harmful effects of eating organic food during pregnancy on symptoms of ADHD and ASD in the offspring. Based on these findings, we do not recommend any specific advice regarding intake of organic food during pregnancy.”

January 27, 2025