Long-Term Use of ADHD Medication Increases Cardiovascular Disease Risk

Long-term use of pharmacotherapy to treat attention-deficit/hyperactivity disorder (ADHD) is associated with an increased risk for cardiovascular disease (CVD), according to study results published in JAMA Psychiatry. Given that ADHD medication use has substantially increased in recent years, a better understanding of the potential long-term side effects of these medications is critical to patient safety.

While ADHD medications have repeatedly demonstrated treatment efficacy in clinical trials, it remains unclear whether the increases in blood pressure and heart rate that are commonly associated with these medications increase the risk for CVD in the long term. Accordingly, investigators conducted a case-control study to determine the association between CVD and commonly prescribed ADHD medications.

The investigators used nationwide Swedish register databases to identify individuals who received an incident diagnosis of ADHD or filled a prescription for ADHD medication between January 1, 2007, and December 31, 2020. The main exposure was duration of ADHD medication use, which encompassed both stimulant (ie, methylphenidate, amphetamine, dexamphetamine, lisdexamfetamine) and nonstimulant (ie, atomoxetine, guanfacine) medications. The primary outcome was an incident CVD diagnosis, which included ischemic heart diseases, cerebrovascular diseases, hypertension, heart failure, arrhythmias, thromboembolic disease, arterial disease, and other forms of CVD.

The investigators identified a total of 278,027 individuals with ADHD. The median age of participants was 34.6 years and 59.2% were boys/men. Cases of individuals with ADHD and an incident CVD diagnosis were matched with up to 5 controls (ADHD without CVD) based on age, sex, and follow-up duration. The median follow-up time was 4.1 years.

The investigators found that a longer cumulative duration of ADHD medication use was associated with an increased risk for CVD, relative to nonuse. The adjusted odds ratio (aOR) was 0.99 (95% CI, 0.93-1.06) for 0 to 1 year of ADHD medication use, 1.09 (95% CI, 1.01-1.18) for 1 to 2 years, 1.15 (95% CI, 1.05-1.25) for 2 to 3 years, peaked at 1.27 (95% CI, 1.17-1.39) with 3 to 5 years of use, but remained elevated at 1.23 (95% CI, 1.12-1.36) for usage beyond 5 years. Throughout the follow-up period, each additional year of medication use corresponded to a 4% increased risk for CVD (aOR, 1.04; 95% CI, 1.03-1.05). Furthermore, the investigators noted that CVD risk increased in a dose-dependent manner, as higher average daily doses of medications were associated with elevated risk.

The most prevalent CVD types among the cases were hypertension (40.5%) and arrhythmias (12.6%). Specifically, ADHD medication use for 3 to 5 years was associated with a 72% increased risk for hypertension (aOR, 1.72; 95% CI, 1.51-1.97) and a 65% increased risk for arterial disease (aOR, 1.65; 95% CI, 1.11-2.45).
Overall, the investigators found a 23% increased risk for CVD among individuals using ADHD medications for more than 5 years. Study authors concluded, “These findings highlight the importance of carefully weighing potential benefits and risks when making treatment decisions about long-term ADHD medication use.”

Study limitations include the potential underdiagnosis of CVD in controls, a lack of information regarding ADHD medication adherence, the exclusion of individuals with preexisting CVD, and an inability to determine causality due to the observational study design.

Disclosure: One study author declared affiliations with biotech and pharmaceutical companies. Please see the original reference for a full list of author disclosures.

This article originally appeared on Psychiatry Advisor