REVIEW OF: Zhang L et al,  JAMA Psychiatry 2024;81(2):178–187

STUDY TYPE: Nested case-control study

ADHD medications are effective tools for managing symptoms, but questions persist about their long-term safety. This Swedish study reveals a modest yet significant link between prolonged use of both stimulant (methylphenidate and dextroamphetamine) and nonstimulant (atomoxetine, guanfacine) ADHD medications and increased cardiovascular risk, particularly hypertension and arterial disease.

The study assessed 278,027 individuals aged 6–64 years with ADHD or ADHD medication use, using Swedish health registers spanning 2007–2020. Cases (10,388 individuals) had new cardiovascular disease (CVD) diagnoses, while controls (51,672 individuals) were matched by age and sex but had no CVD. Cardiovascular outcomes included hypertension, arterial disease, ischemic heart disease, and cerebrovascular events.

Cumulative ADHD medication use was analyzed in terms of duration and dose. Adjustments were made for factors such as comorbidities (eg, diabetes, obesity, psychiatric conditions) and socioeconomic status.

Results from the study were as follows: 

Cumulative risk: Each year of ADHD medication use increased CVD risk by 4%, with risks stabilizing after three years. Over five years, stimulant use was linked to a total 25% increased CVD risk.

Top risks: The most common types of CVD in cases were hypertension (4,210 cases [40.5%]) and ­arrhythmias (1,310 cases [12.6%]).

Hypertension: This was the most significant finding, with adjusted odds ratios (AORs) of 1.72 (3–5 years) and 1.80 (>5 years).

Arterial disease (atherosclerosis, aortic aneurysm and dissection, other aneurysm, other peripheral vascular diseases, arterial embolism and thrombosis): Results showed a moderate risk increase (AOR 1.65 for 3–5 years).

Dose dependence: Higher doses (≥1.5 defined daily dosages, eg, >45 mg/day of methylphenidate) correlated with greater CVD risk.

Medication type: Stimulants carried higher risks than nonstimulants like atomoxetine, which showed a lower, one-year increase.

Consistency across groups: Findings were similar regardless of age (≤25 vs >25 years) and sex. Note the cases had less educational achievement on average than controls. 

CARLAT TAKE

Undertreatment of ADHD is itself a substantial and extensive risk factor for diabetes, obesity, hypertension, and shortened lifespan (www.tinyurl.com/4esuat26). Also, preexisting CVD in controls or cases could have underestimated the true risk. That said, it is no surprise that long-term ADHD medication use, particularly stimulants, modestly increases cardiovascular risks. However, the study cannot establish causation, as we know ADHD is associated with CVD risk factors like obesity and diabetes. 

For clinicians:

Monitor cardiovascular health: Regular blood pressure and cardiovascular checks are essential.

Use caution with high doses: Avoid exceeding 1.5 times defined daily dosages when possible, particularly in patients with preexisting cardiovascular risks.

Encourage nonpharmacologic strategies: Lifestyle changes, such as improving diet, increasing exercise, and addressing sleep issues, can help minimize reliance on high-dose, long-term medications.

Reassess long-term use: These findings underscore the need for periodic evaluation of whether ADHD medications remain necessary, particularly at higher doses.