Long-term use of ADHD medications associated with increased cardiovascular disease

Research from Karolinska Institutet, Sweden, found an increased risk of cardiovascular disease associated with long-term use of ADHD medications. Specific associations with different medications and dosages were linked to hypertension and arterial disease, with a higher risk observed for stimulant medications.

In an article titled “Medications for attention-deficit/hyperactivity disorder and long-term risk of cardiovascular disease,” published in JAMA PsychiatryThe team used a case-control study to examine the cardiovascular disease (CVD) consequences of long-term use of medications for attention-deficit/hyperactivity disorder (ADHD).

In a robust cohort of 278,027 people with ADHD aged 6 to 64 years, the incidence rate of cardiovascular disease was 7.34 per 1,000 person-years. The study analyzed 10,388 cases (with CVD) and 51,672 matched controls and observed higher rates of CVD in cases compared to controls.

The cases were identified based on recorded diagnoses of various types of cardiovascular diseases, including ischemic heart disease, cerebrovascular disease, hypertension, heart failure, arrhythmias, thromboembolic disease, arterial disease and others forms of heart disease.

Controls were selected to match cases regarding age, gender, and calendar time. These were individuals who had not been diagnosed with cardiovascular disease at the time their corresponding case was diagnosed with cardiovascular disease.

Meta-analyses of previous randomized clinical trials have reported increases in heart rate and blood pressure associated with stimulant and non-stimulant medications for ADHD. Clinical trials tended to be of shorter duration, hence the need for longer-term follow-up.

In the current study, researchers found that long-term use of the stimulant methylphenidate had an adjusted odds ratio for increased risk of cardiovascular disease of 20% for 3 to 5 years of use and 19% for users over 5 years old. Lisdexamfetamine was associated with an elevated risk of cardiovascular disease of 23% for 2 to 3 years and 17% for more than 3 years of use.

Non-stimulant atomoxetine had an increased association with cardiovascular disease, which was only significant for the first year of use, at 7%.

ADHD is a common psychiatric illness characterized by inattention, impulsivity, and hyperactivity. Pharmacological treatment often includes stimulants such as methylphenidate (Ritalin, Concerta) and dextroamphetamine-AMP (Adderall). These stimulants would make most people nervous, excited, and anxious, but calm people with ADHD, allowing them a greater ability to concentrate.

Stimulants may seem counterintuitive as a treatment for people with symptoms of hyperactivity. By binding to presynaptic dopamine transporters or blocking reuptake mechanisms, stimulants help restore levels of catecholamines (hormonal neurotransmitters) repressed in ADHD patients.

Atomoxetine (Strattera) is a non-stimulant medication that affects the norepinephrine reuptake mechanism. While effective for some, it only manages symptoms in about 30% of patients, compared with about 70% of those taking stimulants.

Non-stimulants used in the treatment of ADHD are sometimes formulations of tricyclic antidepressants. These can be effective in treating ADHD symptoms, but have been associated with cardiac arrhythmias and, as with any antidepressant use, off-target behavioral or psychological side effects have been reported.

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