Which antidepressant does not cause QT (quantitative electrocardiogram interval) prolongation when co-administered with amiodarone (antiarrhythmic medication)?

Antidepressants That Do Not Cause QT Prolongation with Amiodarone

Bupropion is the safest antidepressant choice when co-administered with amiodarone as it does not cause QT prolongation and has minimal drug interactions with amiodarone.

Understanding the Risk of QT Prolongation

Amiodarone is known to markedly prolong the QT interval, although it paradoxically has a relatively low risk of causing Torsades de Pointes (TdP) compared to other QT-prolonging medications 1. However, when combined with other medications that also prolong the QT interval, the risk of dangerous arrhythmias increases significantly.

Mechanism of Risk

• Amiodarone inhibits multiple CYP enzymes (CYP2D6, CYP3A4) which metabolize many antidepressants 2
• This can increase plasma concentrations of SSRIs and other antidepressants
• Concurrent use creates an additive effect on QT prolongation 2

Antidepressant Options with Amiodarone

Recommended Options:

1. Bupropion - First choice

   • Does not prolong QT interval
   • Not metabolized primarily by CYP pathways inhibited by amiodarone
   • No significant cardiac conduction effects

2. Mirtazapine - Second choice

   • Minimal effect on QT interval
   • Different metabolic pathway than most SSRIs

Antidepressants to Avoid:

• Tricyclic antidepressants (amitriptyline, imipramine, etc.)

  • High risk of QT prolongation and TdP 1
  • Significant risk when combined with amiodarone

• Citalopram/Escitalopram

  • Known dose-dependent QT prolongation
  • Increased risk when combined with amiodarone

• Fluoxetine

  • Case reports of TdP when combined with amiodarone 3
  • A 62-year-old male experienced QTc prolongation and TdP after concurrent administration of fluoxetine and amiodarone 3

• Paroxetine

  • The American Heart Association recommends avoiding this combination 2

Risk Factors for QT Prolongation

Patients at highest risk when taking amiodarone with antidepressants include:

• Age >65 years
• Female sex
• Pre-existing cardiovascular disease
• Bradycardia
• Electrolyte abnormalities (hypokalemia, hypomagnesemia)
• Concomitant use of other QT-prolonging medications 2

Monitoring Recommendations

If an antidepressant must be used with amiodarone:

1. Obtain baseline ECG to measure QTc interval
2. Check electrolytes (potassium, magnesium, calcium)
3. Monitor ECG within 3-5 days of starting combination therapy
4. Discontinue if QTc exceeds 500 ms or increases ≥60 ms from baseline 2
5. Monitor for signs of serotonin syndrome

Clinical Considerations

• Amiodarone has a very long half-life (up to 100 days), so interactions can persist for weeks after discontinuation
• Even "safer" antidepressants should be started at lower doses and titrated slowly when used with amiodarone
• Consider cardiology consultation before initiating combination therapy in high-risk patients

Common Pitfalls to Avoid

1. Assuming all SSRIs have equal risk with amiodarone
2. Failing to monitor QTc interval when initiating combination therapy
3. Overlooking the importance of electrolyte monitoring and correction
4. Not considering the patient's baseline cardiac risk factors
5. Forgetting that amiodarone's long half-life means interactions can persist long after discontinuation

Remember that while amiodarone itself rarely causes TdP despite QT prolongation, adding another QT-prolonging medication significantly increases this risk. When possible, choose antidepressants with minimal effect on cardiac conduction.