A large-scale analysis of 102 randomized controlled trials has found that medications used to treat attention deficit hyperactivity disorder (ADHD) have only modest effects on the cardiovascular system, researchers report in a new study published in The Lancet Psychiatry.
The international research team, led by the University of Southampton, conducted the most comprehensive assessment to date of how ADHD medications affect blood pressure, heart rate, and electrocardiogram (ECG) parameters in both pediatric and adult populations.
Small Cardiovascular Changes Observed Across Medication Types
The systematic review and network meta-analysis included data from 22,702 participants with ADHD, comprising 13,315 children and adolescents and 9,387 adults. Most participants were male (73% of children/adolescents and 57% of adults) and White (71% of children/adolescents and 79% of adults).
"We found an overall small increase in blood pressure and pulse for the majority of children taking ADHD medications," said senior lead author Professor Samuele Cortese, MD, PhD, from the University of Southampton. "Other studies show clear benefits in terms of reductions in mortality risk and improvement in academic functions, as well as a small increased risk of hypertension, but not other cardiovascular diseases."
In children and adolescents, the mean increases in systolic blood pressure compared to placebo ranged from 1.07 mmHg with atomoxetine to 1.81 mmHg with methylphenidate. For diastolic blood pressure, increases ranged from 1.93 mmHg with amphetamines to 2.42 mmHg with methylphenidate. Pulse rate increases varied from 2.79 beats per minute with viloxazine to 5.58 beats per minute with atomoxetine.
Similar modest effects were observed in adults, with systolic blood pressure increases ranging from 1.66 mmHg with methylphenidate to 2.3 mmHg with amphetamines. Diastolic blood pressure increased between 1.60 mmHg with methylphenidate and 3.07 mmHg with lisdexamfetamine, while pulse rate increases ranged from 4.37 beats per minute with methylphenidate to 5.8 beats per minute with viloxazine.
Guanfacine Shows Opposite Effect
Unlike other ADHD medications, guanfacine was associated with decreases in cardiovascular parameters. In children and adolescents, guanfacine reduced systolic blood pressure by approximately 2.83 mmHg, diastolic blood pressure by 2.08 mmHg, and pulse by 4.06 beats per minute compared to placebo.
The effect was even more pronounced in adults, with decreases of about 10.1 mmHg in systolic blood pressure, 7.73 mmHg in diastolic blood pressure, and 6.83 beats per minute in pulse rate.
Stimulants vs. Non-Stimulants: Similar Cardiovascular Profiles
Contrary to common assumptions, the study found no significant differences between stimulants (such as methylphenidate and amphetamines) and non-stimulants (such as atomoxetine and viloxazine) regarding their effects on blood pressure and heart rate.
"Our findings should inform future clinical guidelines, stressing the need to systematically monitor blood pressure and heart rate, both for stimulants and non-stimulants," said Dr. Luis Farhat from the University of São Paulo, Brazil, the study's first author. "This should be particularly relevant for practitioners who might assume that only stimulants have a negative effect on the cardiovascular system."
Clinical Implications and Recommendations
The researchers emphasize that while the cardiovascular effects are generally small at the group level, individual responses may vary. They recommend routine monitoring of blood pressure and heart rate for all patients with ADHD who are receiving pharmacological treatment, regardless of the specific medication prescribed.
"While our findings are informative at the group level, that is, on average, we cannot exclude that a subgroup of individuals may have a higher risk of more substantial cardiovascular alterations," Professor Cortese noted. "While it is currently not possible to identify those individuals at higher risk, efforts based on precision medicine approaches will hopefully provide important insights in the future."
For patients with pre-existing cardiovascular conditions, the researchers advise consultation with a specialist cardiologist before initiating ADHD medication.
Study Limitations and Future Research
The authors acknowledge that most of the analyzed trials had relatively short follow-up periods (median of 7 weeks), with only four studies providing data on medium-term effects and none on long-term outcomes. They call for additional research to investigate the causal effects of ADHD medications on cardiovascular parameters over longer periods.
The research team plans to explore whether certain subgroups might be more vulnerable to cardiovascular side effects than others, potentially leading to more personalized treatment approaches.
The study was funded by the National Institute for Health and Care Research (NIHR) within the framework of the NIHR Research Professorships scheme to Professor Cortese, with Professor Alexis Revet from the University of Toulouse, France, serving as co-senior author.
Balancing Benefits and Risks
With approximately 4% of children in the UK affected by ADHD, and about 45% of those receiving medication, these findings provide reassurance about the cardiovascular safety of ADHD treatments when appropriately monitored.
"When it comes to taking any medication, risks and benefits should always be assessed together," Professor Cortese emphasized. "Overall, the risk-benefit ratio is reassuring for people taking ADHD medications."
The study's conclusions align with previous research showing that ADHD medications provide significant benefits, including improved academic function and reduced mortality risk, which generally outweigh the modest cardiovascular effects observed in most patients.
