Cardiovascular Safety of Atomoxetine and Methylphenidate in Patients With Attention-Deficit/Hyperactivity Disorder in Japan: A Self-Controlled Case Series Study

J Atten Disord. 2024 Feb;28(4):439-450. doi: 10.1177/10870547231214993. Epub 2023 Dec 12.

Abstract

Objective: To investigate the association between atomoxetine or methylphenidate use and arrhythmia, heart failure (HF), stroke, and myocardial infarction (MI) in attention-deficit/hyperactivity disorder (ADHD) patients mainly focused on the people of working age.

Methods: In a self-controlled case series study using a Japanese claims database, we identified events of arrhythmia, HF, stroke, and MI among 15,472 atomoxetine new users and 12,059 methylphenidate new users. Adjusted incidence rate ratios (aIRRs) of outcome events were estimated using multivariable conditional Poisson regression.

Results: An increased risk of arrhythmia was observed during the first 7 days after the initial atomoxetine exposure (aIRR 6.22, 95% CI [1.90, 20.35]) and in the subsequent exposure (3.23, [1.58, 6.64]). No association was found between methylphenidate exposure and arrhythmia, nor between atomoxetine or methylphenidate exposure and HF. The limited number of stroke and MI cases prevented thorough analysis.

Conclusions: Clinicians should consider monitoring for arrhythmia after patients initiating or re-initiating atomoxetine.

Keywords: ADHD; Atomoxetine; Cardiovascular events; Methylphenidate; Selfcontrolled case series study.

MeSH terms

  • Adrenergic Uptake Inhibitors / adverse effects
  • Arrhythmias, Cardiac / chemically induced
  • Arrhythmias, Cardiac / drug therapy
  • Atomoxetine Hydrochloride / adverse effects
  • Attention Deficit Disorder with Hyperactivity* / chemically induced
  • Attention Deficit Disorder with Hyperactivity* / drug therapy
  • Attention Deficit Disorder with Hyperactivity* / epidemiology
  • Central Nervous System Stimulants* / adverse effects
  • Humans
  • Japan / epidemiology
  • Methylphenidate* / adverse effects
  • Stroke* / chemically induced
  • Stroke* / drug therapy

Substances

  • Methylphenidate
  • Atomoxetine Hydrochloride
  • Central Nervous System Stimulants
  • Adrenergic Uptake Inhibitors