ADHD Medications and Cardiovascular Events in Adults

The use of medications intended for the treatment of attention-deficit/hyperactivity disorder (ADHD) by adults increased more rapidly than did use of those medications by children between 2001 and 2010. A US Food and Drug Administration advisory committee on ADHD medication safety stated that >1.5 million adults were taking stimulants in 2005, and nearly 32% of all prescriptions written were for adults. Adults diagnosed with ADHD are typically treated with the stimulant classes methylphenidate and amphetamine and, increasingly, with atomoxetine, a nonstimulant agent. Studies have shown that stimulants and atomoxetine elevate systolic blood pressure levels by 2 to 5 mm Hg and diastolic blood pressure levels by 1 to 3 mm Hg; the medications also lead to increases in heart rate. According to researchers, although these effects may slightly increase the risk for myocardial infarction (MI), sudden cardiac death (SCD), and stroke, there have not been sufficiently large clinical trials to accurately determine the risk of these events. The researchers recently conducted a retrospective, population-based cohort study using electronic healthcare records from 4 study sites to assess whether current use of medications intended to treat ADHD is associated with increased risk of cardiovascular events in young and middle-aged adults. They reported study results online in the Journal of the American Medical Association [2011;306(24):doi:10.1001/jama.2011.1830]. The primary outcome measures were serious cardiovascular events, including MI, SCD, or stroke, with comparison between current or new users and remote users (>364 days since end of last days supply) to account for potential healthy-user bias. Participants were adults 25 through 64 years of age with dispensed prescriptions for methylphenidate, amphetamine, or atomoxetine at baseline. Each medication user (n=150,359) was matched to 2 nonusers based on study site, birth year, sex, and calendar year (443,198 total users and nonusers). There were 806,182 person-years of follow-up, during which 1357 cases of MI, 296 cases of SCD, and 575 cases of stroke occurred. There were 107,322 person-years of current use with a crude incidence per 1000 person-years of 1.34 (95% confidence interval [CI], 1.14-1.57) for MI, 0.30 (95% CI, 0.20-0.42) for SCD, and 0.56 (95% CI, 0.43-0.72) for stroke. The multivariable-adjusted rate ratio (RR) of serious cardiovascular events for current use compared with nonuse of ADHD medications was 0.83 (95% CI, 0.72-0.96). Results were similar for specific medications and across end points. RRs were also similar for ischemic or hemorrhagic stroke. In the new user cohort, baseline characteristics of new users of ADHD medication were generally similar to characteristics of all ADHD medication users. Cardiovascular diseases were similar or slightly more prevalent in new users compared with nonusers. In the new-user analyses, RRs for current versus remote use were close to 1.0 for MI, stroke, and the combined end point. For the combined end point, there was no pattern of increasing risk with increasing duration of current use or for any window of time. Study limitations cited by the authors include basing use of ADHD medications on electronic pharmacy records of filled prescriptions, which may not represent medications actually consumed; likewise, days supply may not represent actual periods of use. In addition, because the study did not include adults ≥65 years of age, the results are not generalizable to that age group.