Bupropion and QTc Interval Effects
Bupropion (Wellbutrin) does not cause QTc prolongation at therapeutic doses, but can cause significant QTc prolongation and QRS widening in overdose situations. 1, 2
Effects at Therapeutic Doses
Bupropion has no clinically significant effect on QTc interval when used at prescribed doses. A cross-sectional study of 487 subjects with 798 EKG records found no QTc prolongation with therapeutic bupropion use. 1
Bupropion is notably absent from comprehensive lists of QT-prolonging psychiatric medications in major cardiology guidelines, unlike many antidepressants (TCAs, citalopram) and antipsychotics that carry established arrhythmia risks. 3, 4
Some data suggested bupropion might have a "QTc-sparing" effect when combined with other QT-prolonging medications, but this was not confirmed in clinical studies. 1
Effects in Overdose
In overdose situations, bupropion causes significant cardiotoxicity including QTc prolongation and QRS widening. 5, 6, 7, 2
Specific Overdose Findings:
QTc prolongation and QRS widening occur when serum bupropion levels are elevated, with cardiotoxicity peaking at levels around 334 ng/mL (well above therapeutic range). 7
The cardiotoxicity appears directly related to the parent drug (bupropion) rather than its metabolite hydroxybupropion, as ECG abnormalities resolve when bupropion levels fall into therapeutic range even while metabolite levels remain elevated. 7
Overdose cases have required aggressive cardiac monitoring and antidysrhythmic therapy for up to 80 hours post-ingestion. 6
The mechanism likely involves effects on potassium rectifier channels (Kir) and/or Connexin 43 at cardiac gap junctions. 5
Clinical Monitoring Recommendations
Routine ECG monitoring is not required for patients on therapeutic doses of bupropion. 3, 1
When to Monitor:
In suspected overdose, obtain immediate ECG and monitor continuously for QRS widening and QTc prolongation. 6, 7
If QTc reaches >500 ms or increases >60 ms from baseline in any clinical scenario, discontinue the medication immediately. 3
Consider enhanced monitoring if bupropion is combined with other medications in overdose situations, as combination toxicity (e.g., with ziprasidone) can worsen cardiotoxicity. 6
Risk Stratification
The highest risk for QT prolongation with bupropion exists exclusively in overdose situations, not therapeutic use. 2