Can Trazodone cause QT(c) (QT interval correction) prolongation?

Trazodone and QTc Prolongation

Yes, trazodone can cause QTc prolongation, particularly in overdose situations or when combined with other QT-prolonging medications. While not among the highest-risk antidepressants for this effect, evidence shows trazodone has demonstrated QT-prolonging properties in both clinical and laboratory settings 1, 2.

Evidence for Trazodone's QT Effects

The American Heart Association and American College of Cardiology Foundation specifically mention trazodone in their scientific statement on prevention of torsade de pointes (TdP) in hospital settings, noting that trazodone has been implicated in TdP in patients with purposeful overdose 3.

Laboratory studies confirm this risk:

• Trazodone inhibits hERG channel current (responsible for cardiac repolarization) with an IC50 of 0.69 microM, which is within clinically relevant concentrations 2
• In rabbit heart preparations, trazodone increased both QT interval and action potential duration in a reverse frequency-dependent manner at clinically relevant concentrations 2

Risk Factors for Trazodone-Induced QT Prolongation

The risk of QTc prolongation with trazodone increases with:

1. Overdose situations - Case reports document significant QT prolongation in overdose 1, 4
2. Drug combinations - Particularly when combined with other QT-prolonging medications 5
3. Pre-existing cardiac disease - The FDA label warns that trazodone should be used with caution in patients with cardiac disease 6
4. Other risk factors for TdP, including:
   • Older age
   • Female sex
   • Electrolyte abnormalities (especially hypokalemia or hypomagnesemia)
   • Bradycardia
   • Genetic predisposition to QT prolongation 3

Clinical Significance

While trazodone can cause QT prolongation, its risk profile differs from high-risk medications:

• Trazodone is not listed in the highest-risk category of QT-prolonging drugs in most guidelines
• A 2022 study found that trazodone was associated with prolonged QTc (>500ms) in poison center exposures, though life-threatening dysrhythmias remained rare 7
• The FDA label for trazodone mentions that it "may be arrhythmogenic in some patients" with pre-existing cardiac disease, noting observed arrhythmias including PVCs, ventricular couplets, and short episodes of ventricular tachycardia 6

Monitoring Recommendations

For patients on trazodone:

1. Baseline ECG is advisable for patients with:

   • Pre-existing cardiac disease
   • Multiple risk factors for QT prolongation
   • Concurrent use of other QT-prolonging medications

2. Follow-up ECG when:

   • Increasing to high doses
   • Adding other QT-prolonging medications
   • Patient develops symptoms suggesting arrhythmia

3. Immediate ECG assessment if a patient presents with trazodone overdose 1

Management of QT Prolongation

If QT prolongation occurs:

• Consider dose reduction or discontinuation if QTc exceeds 500ms or increases by >60ms from baseline 3
• Monitor and correct electrolyte abnormalities, particularly potassium and magnesium
• Avoid adding other QT-prolonging medications
• Consider alternative antidepressants with lower QT risk if prolonged QTc persists

Conclusion

While trazodone is not among the highest-risk medications for QT prolongation, clinicians should be aware of this potential adverse effect, especially in patients with risk factors or in overdose situations. The risk of serious arrhythmias like TdP appears to be low with therapeutic dosing in patients without additional risk factors, but appropriate monitoring is warranted in high-risk populations.