What is the percentage of arrhythmia associated with bupropion (Wellbutrin)?

From the Guidelines

Bupropion is associated with a low risk of arrhythmias, with the most recent study suggesting an incidence of approximately 0.1% to 0.4% in patients taking therapeutic doses 1. The risk of arrhythmias with bupropion increases at higher doses, particularly above 450mg daily.

• Patients with pre-existing cardiovascular disease, electrolyte abnormalities, or those taking other QT-prolonging medications may be at higher risk.
• The arrhythmogenic potential of bupropion is related to its effects on cardiac ion channels, particularly potassium channels, which can prolong the QT interval.
• Seizures, which occur in about 0.4% of patients at therapeutic doses, can also trigger secondary cardiac arrhythmias, as noted in the study on naltrexone ER/bupropion 1. For patients with cardiac risk factors, starting at a lower dose (such as 150mg daily) with gradual titration and monitoring for symptoms like palpitations, dizziness, or syncope is recommended.
• Immediate-release formulations carry a slightly higher risk than sustained-release or extended-release versions due to higher peak plasma concentrations.
• If arrhythmias occur, dose reduction or discontinuation may be necessary, and alternative antidepressants with lower arrhythmogenic potential should be considered, as suggested by the study on phentermine/topiramate ER and naltrexone ER/bupropion 1. The most recent and highest quality study available, published in 2023, provides the best evidence for the risk of arrhythmias with bupropion 1.

From the FDA Drug Label

The following additional adverse reactions occurred in controlled trials of bupropion HCl immediate-release (300 to 600 mg per day) at an incidence of at least 1% more frequently than in the placebo group were: cardiac arrhythmia (5% vs. 4%)

• Cardiac arrhythmia occurred in 5% of patients treated with bupropion HCl immediate-release, compared to 4% in the placebo group 2.

From the Research

Arrhythmia with Bupropion

• The exact percentage of arrhythmia with bupropion is not directly stated in the provided studies, but several studies report on the cardiovascular effects of bupropion.
• A study from 1991 3 found that bupropion did not exacerbate ventricular arrhythmias in patients with preexisting heart disease.
• Another study from 2023 4 reported that 1.47% of patients with bupropion exposures experienced adverse cardiovascular events, including ventricular dysrhythmias.
• A 2024 study 5 found that 9.6% of patients with bupropion overdose experienced adverse cardiovascular events, including ventricular dysrhythmia.
• The same study 5 reported that initial serum bicarbonate < 20 mEq/L and initial QTc ≥ 500 ms independently predicted adverse cardiovascular events.

Predictors of Arrhythmia

• Several studies identified predictors of adverse cardiovascular events, including:
  • Initial serum bicarbonate < 20 mEq/L 5
  • Initial QTc ≥ 500 ms 5
  • Initial serum lactate > 5.2 mmol/L 5
  • Age 4
  • Seizures 4
  • QRS widening 4
  • QTc prolongation 4
• A 2024 study 6 found that maximum heart rate in eight hours was associated with a risk of adverse outcomes, including dysrhythmias.

Cardiovascular Effects

• Bupropion is generally considered to be relatively free of cardiac side effects in depressed patients without cardiac disease 3.
• However, bupropion can cause adverse cardiovascular events, including ventricular dysrhythmias, in patients with preexisting heart disease or in cases of overdose 3, 5, 4.