results of a large Swedish nested case-control study suggest.
The increased risk was evident only for hypertension and arterial disease, was dose dependent, and was higher for stimulant than nonstimulant ADHD medications.
“Clinicians should be vigilant in monitoring signs and symptoms of cardiovascular diseases, particularly among those receiving higher doses,” Zheng Chang, PhD, principal researcher, department of medical epidemiology and biostatistics, Karolinska Institutet, Stockholm, said in an interview.
“Treatment decisions, as always, should be based on careful weighing of potential benefits and risks at individual patient level, rather than simple one-size-fits-all recommendations,” Dr. Chang added.
The study was published online in JAMA Psychiatry
Filling in the research gaps
The use of medications to treat ADHD has increased markedly over the past decades in both children and adults. The potential risk for CVD associated with long-term ADHD medication use remains unclear. Most “longitudinal” studies that have looked at the association have an average follow-up time of no more than 2 years, the authors note.
In contrast, the Swedish study assessed the association between cumulative use of ADHD medication in children and adults followed for up to 14 years and also looked at whether associations differ across types of medication and dosages, types of CVD, gender, and age.
Among 278,027 individuals aged 6-64 years diagnosed with ADHD or dispensed ADHD medication, 10,388 with CVD were identified and matched to 51,672 controls without CVD.
Longer cumulative duration of ADHD medication use was associated with a statistically significant increased risk for CVD, compared with no use.
When the risk for specific CVDs was examined, long-term use of ADHD medication (compared with no use) was associated with an increased risk for hypertension and arterial disease but not arrhythmias, heart failure, ischemic heart disease, thromboembolic disease, or cerebrovascular disease.
For hypertension, the adjusted odds ratio was 1.72 (95% confidence interval, 1.51-1.97) for 3 to ≤ 5 years and 1.80 (95% CI, 1.55-2.08) for > 5 years of medication use. For arterial disease, the AOR was 1.65 (95% CI, 1.11-2.45) for 3 to ≤ 5 years and 1.49 (95% CI, 0.96-2.32) for > 5 years of use.
Stimulants confer greatest risk
Across the 14-year follow-up period, each additional year of ADHD medication use was associated with an average 4% increased CVD risk, with a larger 8% increased risk in the first 3 years of cumulative use, followed by stable risk over the remaining follow-up.
Similar risks were observed in children and adults, as well as in females and males.
When focusing on specific ADHD medications, compared with no use, long-term use of the stimulant methylphenidate was associated with an increased risk for CVD (AOR, 1.20 [95% CI, 1.10-1.31] for 3 to ≤ 5 years and 1.19 [95% CI, 1.08-1.31] for > 5 years).
The same was true for long-term use of the stimulant lisdexamfetamine (AOR, 1.23 [95% CI, 1.05-1.44] for 2 to ≤ 3 years and 1.17 [95% CI, 0.98-1.40] for > 3 years).
In contrast, use of the nonstimulant atomoxetine was associated with elevated CVD risk only for the first year of use (AOR, 1.07; 95% CI, 1.01-1.13).
The increased risk for CVD occurred only above certain average daily doses: 45 mg for methylphenidate and lisdexamfetamine, 22.5 mg for amphetamines, and 120 mg for atomoxetine.
The authors note that, although they accounted for a wide range of potential confounding variables, considering the observational nature of the study and the possibility of residual confounding, they could not prove causality.