Cardiovascular adverse events associated with norepinephrine–dopamine reuptake inhibitors: a pharmacovigilance study of the FDA Adverse Event Reporting System

Abstract

Norepinephrine–dopamine reputake inhibitors (NDRIs), including bupropion, methylphenidate, atomoxetine, and reboxetine, are commonly prescribed for psychiatric disorders such as narcolepsy, attention-deficit/hyperactivity disorder, and depression. Cardiovascular adverse events have been reported to the FDA despite their effectiveness. This pharmacovigilance study analyzed cardiovascular adverse events associated with NDRIs using the FDA Adverse Event Reporting System data from January 2004 to December 2021. A retrospective analysis of adverse event reports was conducted, employing time-trend analysis and disproportionality evaluation to assess cardiovascular risks. Bupropion had the greatest reported odds ratios (RORs) for tachycardia (ROR = 4.2, 95% CI: 4.0–4.4) and hypertension (ROR = 3.5, 95% CI: 3.3–3.7), while methylphenidate showed greater ROR for arrhythmias (ROR = 2.8, 95% CI: 2.6–3.0) and palpitations (ROR = 3.1, 95% CI: 2.9–3.3). Reboxetine had signals for palpitations (ROR = 3.0, 95% CI: 2.8–3.2) and myocardial infarction (ROR = 2.7, 95% CI: 2.5–2.9), whereas atomoxetine revealed signals for hypertension (ROR = 2.9, 95% CI: 2.7–3.1) and syncope (ROR = 2.5, 95% CI: 2.3–2.7). Time-trend analysis revealed temporal variability in the cardiovascular risks connected with NDRIs. Our research elucidates cardiovascular safety profiles for NDRIs, highlighting the necessity for continuous pharmacovigilance. The observed variations in adverse events emphasize the need for ongoing surveillance to mitigate potential cardiovascular risks and enhance patient safety and treatment outcomes.