Can Wellbutrin (bupropion) prolong the QTc interval?

From the Guidelines

Wellbutrin (bupropion) generally does not significantly prolong the QTc interval at standard therapeutic doses. Unlike many other antidepressants, bupropion has a relatively favorable cardiac safety profile with respect to QTc prolongation, as noted in various studies 1. However, there have been rare case reports of QTc prolongation with bupropion, particularly in overdose situations or when combined with other QTc-prolonging medications.

Key Considerations

• The mechanism behind bupropion's cardiac safety involves its unique pharmacological profile as a norepinephrine-dopamine reuptake inhibitor rather than affecting serotonin or having significant direct effects on cardiac ion channels.
• For patients with pre-existing cardiac conditions, electrolyte abnormalities, or those taking multiple QTc-prolonging medications, caution may still be warranted, as emphasized in guidelines for managing patients with ventricular arrhythmias and preventing sudden cardiac death 1.
• Clinicians should consider baseline ECG monitoring in high-risk patients, though routine ECG monitoring is not generally required for most patients starting bupropion therapy, in line with recommendations for treatment with drugs that have the propensity of prolonging the QT interval 1.
• If a patient experiences symptoms such as palpitations, dizziness, or syncope while on bupropion, cardiac evaluation including ECG assessment would be appropriate, reflecting the importance of monitoring for signs of QT prolongation and torsades de pointes in patients on QT-prolonging medications 1.

Clinical Recommendations

• Bupropion can be used safely in most patients without significant concern for QTc prolongation, but high-risk patients should be monitored closely.
• Baseline ECG and monitoring for QTc prolongation should be considered in patients with risk factors for torsades de pointes, such as hypokalemia, bradycardia, or congenital long QT syndrome, as these conditions can increase the risk of drug-induced torsades de pointes 1.
• Combination with other QTc-prolonging medications should be avoided if possible, and alternative treatments should be considered to minimize the risk of QTc prolongation and torsades de pointes, in accordance with guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death 1.

From the Research

Wellbutrin and QTc Interval Prolongation

• Wellbutrin, also known as bupropion, is an antidepressant that has been linked to QT prolongation in overdose situations 2.
• There is limited data available on the risk of QT/QTc prolongation with bupropion at therapeutic doses, making it difficult to draw conclusions on its risk 2.
• However, it is known that QT prolongation can increase the risk of Torsades de Pointes (TdP), a potentially life-threatening cardiac arrhythmia 3.
• The risk of QTc interval prolongation is generally considered low with newer non-SSRI antidepressants, including bupropion, at therapeutic doses 2.
• Patient-related risk factors, such as female sex, age >65 years, and uncorrected electrolyte disturbances, should be considered when prescribing drugs associated with QT prolongation 3.

Comparison with Other Antidepressants

• Bupropion has been compared to other antidepressants, including SSRIs and non-SSRIs, in terms of its risk of QT prolongation 4, 2.
• Some SSRIs, such as escitalopram, have been shown to have a dose-related risk of QT prolongation, while others, such as fluoxetine and sertraline, have a lower risk 4.
• Non-SSRIs, such as venlafaxine, have also been linked to QT prolongation, particularly in overdose situations 2, 5.
• The risk of QTc interval prolongation should be considered when selecting an antidepressant, particularly in patients with underlying risk factors for TdP 3.