Is Bupropion (Wellbutrin) safe to use in a patient with a known Long QT interval on electrocardiogram (EKG)?

From the Guidelines

Bupropion should be used with caution in patients with known long QT interval on ECG, and its use requires careful consideration of risks versus benefits, as it can potentially contribute to QT prolongation, especially at higher doses or in combination with other QT-prolonging medications. According to the most recent and highest quality study, [ 1 ], a 12-lead ECG should be recorded and the QT interval, corrected for heart rate with Bazett’s or Fridericia’s formula, should be obtained in all patients at baseline. If bupropion is deemed necessary for a patient with long QT syndrome, start with a lower dose (such as 100 mg once daily of immediate-release or 150 mg once daily of extended-release) and monitor closely with follow-up ECGs. Avoid exceeding 450 mg daily total dose. The risk increases with higher doses, electrolyte abnormalities (especially hypokalemia and hypomagnesemia), concomitant QT-prolonging medications, and in patients with structural heart disease. Before initiating bupropion, correct any electrolyte abnormalities and consider alternative medications without QT effects if appropriate.

Key Considerations

• The mechanism of concern is that QT prolongation can predispose patients to developing torsades de pointes, a potentially fatal ventricular arrhythmia [ 1 ].
• Conditions known to provoke torsade de pointes, especially hypokalaemia and extreme bradycardia, should be avoided in patients with drug-induced QT prolongation [ 1 ].
• Exposure to other QT-prolonging drugs should be minimized in patients treated with potentially QT-prolonging medications [ 1 ].
• The QT interval should be evaluated before initiation of treatment and during titration of dose [ 1 ].

Monitoring and Dose Adjustment

• Monitor patients closely with follow-up ECGs, especially when initiating or titrating bupropion [ 1 ].
• Avoid exceeding 450 mg daily total dose of bupropion to minimize the risk of QT prolongation [ 1 ].
• Consider alternative medications without QT effects if appropriate, especially in patients with structural heart disease or other risk factors for torsades de pointes [ 1 ].

From the Research

Bupropion and QT Interval Prolongation

• Bupropion is an antidepressant medication that may be considered for use in patients with a known Long QT interval on electrocardiogram (EKG) 2.
• A cross-sectional study found that bupropion did not affect the relationship between citalopram and QTc interval prolongation, suggesting that bupropion may not increase the risk of QTc interval prolongation 2.
• However, the study also found that bupropion did not have a "QTc-sparing" effect, meaning it did not decrease the risk of QTc interval prolongation 2.

Risk Factors for QT Interval Prolongation

• Patient-related risk factors for QT interval prolongation include female sex, age >65 years, and uncorrected electrolyte disturbances 3.
• The potential risk and degree of QT prolongation associated with the proposed drug, as well as co-prescribed medicines that could increase the risk of QT prolongation, should also be considered 3.
• Other risk factors for drug-induced QT interval prolongation include hypokalemia, hypomagnesemia, heart failure, bradycardia, and genetic predisposition 4.

Monitoring and Management

• Close monitoring for QTc prolongation is necessary to prevent Torsades de Pointes (TdP), a potentially life-threatening cardiac arrhythmia 4.
• When the QTc interval is 470-500 ms for males, or 480-500 ms for females, or the QTc interval increases 60 ms or more from pretreatment values, dose reduction or discontinuation of the offending drug should be considered 4.
• If the QTc interval is ≥500 ms, the offending drug should be discontinued, and continuous EKG telemetry monitoring should be performed, or the 12-lead EKG should be repeated every 2-4 hours, until the QT interval has normalized 4.

Bupropion Safety in Patients with Long QT Interval

• There is limited evidence on the safety of bupropion in patients with a known Long QT interval on EKG 2.
• However, the available evidence suggests that bupropion may not increase the risk of QTc interval prolongation, and may be considered for use in patients with a known Long QT interval on EKG, with close monitoring and management of risk factors 2.