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.

Related posts

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

Northern Finnish Population Study Finds ADHD Slashes Higher Education Attainment, Comorbidity of ADHD + ODD much worse

Background:

Although ADHD typically begins in childhood, its symptoms frequently continue into adulthood, and it is widely acknowledged as having a lifelong prevalence for most persons with ADHD. 

ADHD symptoms are linked to poor academic performance, mainly due to cognitive issues like compromised working memory. These symptoms lead to long-term negative academic outcomes and difficulty in achieving higher educational degrees. 

Oppositional Defiant Disorder (ODD) often co-occurs with ADHD. In community samples, it appears in about 50–60% of those with ADHD. ODD symptoms include an angry or irritable mood, vindictiveness toward others, and argumentative or defiant behavior that lasts more than 6 months and significantly disrupts daily life.  

Since ODD tends to co-occur with ADHD, research on pure ODD groups without ADHD is limited, especially in community samples. This longitudinal study aimed to examine the impact of ADHD and ODD symptoms in adolescence on academic performance at age 16 and educational attainment by age 32. 

Study:

Finland, like other Nordic countries, has a single-payer health insurance system that includes virtually all residents. A Finnish research team used the Northern Finnish Birth Cohort to include all 9,432 children born from July 1, 1985, through June 30, 1986, and followed since then. 

ADHD symptoms were measured at age 16 using the Strengths and Weaknesses of ADHD symptoms and Normal-behaviors (SWAN) scale. 

Symptoms of ODD were screened using a 7-point rating scale similar to the SWAN scale, based on eight DSM-IV-TR criteria: “Control temper”, “Avoid arguing with adults”, “Follow adult requests or rules”, “Avoid deliberately annoying others”, “Assume responsibility for mistakes or misbehaviour”, “Ignore annoyances from others”, “Control anger and resentment”, and “Control spitefulness and vindictiveness.” 

Higher education attainments were determined at age 32. 

Results:

After adjusting for the educational attainments of the parents of the subjects, family type, and psychiatric disorders other than ADHD or ODD, males with ADHD symptoms at age 16 had a quarter, and females a little over a third, of the higher education attainments of peers without ADHD symptoms at age 32.  

With the same adjustments, males with ODD symptoms alone had two-thirds, and females 80%, of the higher education attainments of peers without ODD, but neither outcome was statistically significant. 

However, all participants with combined ADHD and ODD symptoms at age 16 had roughly one-fifth of the higher education attainments of peers without such symptoms upon reaching age 32. 

Interpretation: 

The team concluded, “The findings that emerged from this large longitudinal birth cohort study showed that the co-occurrence of ODD and ADHD symptoms in adolescence predicted the greatest deficits of all in educational attainment in adulthood.” 

This study highlights the significant, long-lasting impact that co-occurring ADHD and ODD symptoms can have on educational outcomes well into adulthood. It underscores the importance of addressing both disorders together during adolescence to help improve future academic success.

July 1, 2025

U.S. Nationwide Study Finds Down Syndrome Associated with 70% Greater Odds of ADHD

The Background:

Down syndrome (DS) is a genetic disorder resulting from an extra copy of chromosome 21. It is associated with intellectual disability. 

Three to five thousand children are born with Down syndrome each year. They have higher risks for conditions like hypothyroidism, sleep apnea, epilepsy, sensory issues, infections, and autoimmune diseases. Research on ADHD in patients with Down syndrome has been inconclusive. 

The Study:

The National Health Interview Survey (NHIS) is a household survey conducted by the National Center for Health Statistics at the CDC. 

Due to the low prevalence of Down syndrome, a Chinese research team used NHIS records from 1997 to 2018 to analyze data from 214,300 children aged 3 to 17, to obtain a sufficiently large and nationally representative sample to investigate any potential association with ADHD. 

DS and ADHD were identified by asking, “Has a doctor or health professional ever diagnosed your child with Down syndrome, Attention Deficit Hyperactivity Disorder (ADHD), or Attention Deficit Disorder (ADD)?” 

After adjusting for age, sex, and race/ethnicity, plus family highest education level, family income-to-poverty ratio, and geographic region, children and adolescents with Down syndrome had 70% greater odds of also having ADHD than children and adolescents without Down syndrome. There were no significant differences between males and females. 

The Take-Away:

The team concluded, “in a nationwide population-based study of U.S. children, we found that a Down syndrome diagnosis was associated with a higher prevalence of ASD and ADHD. Our findings highlight the necessity of conducting early and routine screenings for ASD and ADHD in children with Down syndrome within clinical settings to improve the effectiveness of interventions.” 

June 27, 2025

Meta-analysis Explores Link Between ADHD and Homelessness Among Children and Adolescents

An estimated 150 million children and adolescents live on the streets worldwide. In the U.S., roughly 1.5 million experience homelessness annually. Homelessness increases the risk of health issues, violence, early pregnancy, substance use, vaccine-preventable diseases, mental disorders, suicidal behavior, and early death. 

Rates of anxiety, major depression, conduct disorders, and post-traumatic stress disorder are higher among school-age homeless children compared to their housed peers.  

However, there has been limited attention to ADHD, leading a French research team to conduct a systematic review and meta-analysis of its prevalence among homeless children and adolescents.  

The inclusion criteria required that participants be homeless, under 19 years of age at baseline, and have ADHD identified through a screening tool, self-report, or clinical assessment. 

Results:

Meta-analysis of 13 studies with a combined total of 2,878 individuals found indications of ADHD in almost one in four homeless children and adolescents. There was no sign of publication bias, but considerable variation in estimates across studies. 

The team found a dose-response effect. Meta-analysis of six studies with 1,334 participants under 12 years old reported 13% with indications of ADHD. Meta-analysis of five studies encompassing 991 individuals, 12 through 18 years old, found an ADHD rate of 43%. The ADHD rate among adolescents was 3.3 times greater than among children

There were no significant differences among countries. 

Moreover, limiting the meta-analysis to the seven studies with 1,538 participants that relied on clinical ADHD diagnoses, the gold standard,  resulted in an ADHD prevalence of 23%

The team concluded, “The review of 13 studies revealed that ADHD is common in homeless children and adolescents, suggesting that homelessness may contribute to the development or exacerbation of ADHD symptoms. Conversely, ADHD with other comorbidities may increase the likelihood of homelessness. Reintegrating these children and adolescents into care systems and ensuring access to public health interventions tailored for homeless families and youth is imperative for breaking the cycle of homelessness and improving long-term trajectories.” 

In other words, this review not only confirmed a strong link between homelessness and ADHD in children and youth, but also suggested a complex, cyclical relationship. Providing tailored health care and support for these vulnerable groups is crucial to interrupt this cycle and help improve their future outcomes.

June 23, 2025