Is trazodone (an antidepressant) a long QT (QT interval prolongation) drug?

Trazodone and QT Prolongation Risk

Yes, trazodone is a QT-prolonging drug that has been implicated in Torsades de Pointes (TdP), particularly in overdose situations or when combined with other QT-prolonging medications. 1

Evidence for QT Prolongation Risk

• The FDA drug label explicitly states that "Trazodone Hydrochloride Tablets prolongs the QT/QTc interval" 1
• Trazodone has been implicated in Torsades de Pointes in patients with purposeful overdose 2
• The FDA warns that the use of trazodone should be avoided in patients with known QT prolongation or in combination with other drugs known to prolong QT interval 1
• ECG changes, including QT prolongation, are listed among the most severe reactions reported with trazodone overdose 1

Risk Factors for Trazodone-Induced QT Prolongation

• Pre-existing cardiac disease increases risk of arrhythmias with trazodone 1
• History of cardiac arrhythmias is a contraindication for trazodone use 1
• Symptomatic bradycardia, hypokalemia, or hypomagnesemia increase risk of torsade de pointes with trazodone 1
• Congenital prolongation of the QT interval is a risk factor for trazodone-induced arrhythmias 1
• Concomitant use with other QT-prolonging medications significantly increases arrhythmia risk 1

Drug Interactions That Increase QT Risk

• Trazodone should not be combined with:
  • Class 1A antiarrhythmics (e.g., quinidine, procainamide) 1
  • Class 3 antiarrhythmics (e.g., amiodarone, sotalol) 1
  • Certain antipsychotics (e.g., ziprasidone, chlorpromazine, thioridazine) 1
  • Certain antibiotics (e.g., gatifloxacin) 1
  • Strong CYP3A4 inhibitors (e.g., itraconazole, ketoconazole, clarithromycin) 1

Clinical Significance and Monitoring

• QTc prolongation occurred in 12.2% of trazodone exposure cases reported to poison centers in 2019 3
• A case report documented marked QT prolongation and polymorphous ventricular tachycardia when trazodone was added to amiodarone therapy 4
• In overdose situations, QTc prolongation can be severe, with reports of prolongation up to 586 ms 5
• A dose-response relationship exists for trazodone's effects, with higher doses associated with more severe outcomes 3

Practical Recommendations

• Obtain baseline ECG before initiating trazodone in patients with cardiac risk factors 1
• Consider alternative medications in patients with pre-existing QT prolongation or other cardiac risk factors 1
• Monitor for signs of QT prolongation in patients taking trazodone, especially those on higher doses or with concomitant QT-prolonging medications 1
• Be particularly vigilant in cases of overdose, as QT prolongation is among the most severe reported reactions 1
• If QTc exceeds 500 ms, immediate intervention is warranted as this represents a significant risk threshold 1

Comparison with Other Antidepressants

• Trazodone, while having QT prolongation risk, has been associated with fewer cardiac side effects than tricyclic antidepressants 6
• However, unlike benzodiazepines (such as lorazepam) which have no QT prolongation risk, trazodone does carry this cardiac risk 7
• In a poison center study, trazodone was statistically associated with QTc > 500 ms, along with mirtazapine, amitriptyline, and diphenhydramine 8