Does trazodone increase the QTc (QT interval corrected) interval?

Trazodone and QTc Interval Prolongation

Trazodone can prolong the QTc interval and has been associated with cardiac arrhythmias including torsade de pointes, particularly in patients with preexisting cardiac disease or when combined with other QT-prolonging medications. 1

Evidence for QTc Prolongation

• Trazodone has been implicated in Torsades de Pointes in patients with purposeful overdose, particularly when combined with other QT-prolonging medications 2
• Trazodone inhibits hERG channel current at clinically relevant concentrations with an IC50 of 0.69 microM, similar to other medications known to prolong QT interval 3
• The FDA drug label explicitly states that "Trazodone Hydrochloride Tablets prolongs the QT/QTc interval" 1
• Case reports document QTc prolongation and torsades de pointes even at standard therapeutic doses (50mg daily) 4

Risk Factors for QTc Prolongation with Trazodone

• Preexisting cardiac disease increases risk of arrhythmias with trazodone 1
• History of cardiac arrhythmias 1
• Symptomatic bradycardia 1
• Electrolyte abnormalities (hypokalemia or hypomagnesemia) 1
• Congenital prolongation of QT interval 1
• Concomitant use of other QT-prolonging medications significantly increases risk 1, 5

Monitoring Recommendations

• Consider baseline ECG before initiating trazodone, especially in high-risk patients 6
• For QTc 450-480 ms, identify reversible causes and continue monitoring ECG at least every 8-12 hours 6
• For QTc 481-500 ms, consider more frequent ECG monitoring and correcting electrolyte abnormalities 6
• For QTc >500 ms or increase >60 ms from baseline, temporarily discontinue trazodone 6, 1

Contraindications and Drug Interactions

• Avoid trazodone in patients with known QT prolongation 1
• Avoid combining trazodone with:
  • CYP3A4 inhibitors (e.g., itraconazole, clarithromycin, voriconazole) 1
  • 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

Clinical Implications

• Recent case reports document QTc prolongation with trazodone at standard doses (50mg daily), suggesting risk exists even at therapeutic doses 4
• A 2022 study found that trazodone was statistically associated with QTc >500 ms in poison center exposures 7
• Unlike benzodiazepines (such as lorazepam), which have no QT prolongation risk, trazodone does carry cardiac risk 2, 8
• Trazodone overdose cases have shown QTc prolongation up to 586 ms with associated hypotension 9

Management of Trazodone-Induced QTc Prolongation

• If QTc exceeds 500 ms or increases by >60 ms from baseline, consider temporary discontinuation of trazodone 6, 1
• Correct any electrolyte abnormalities, particularly potassium and magnesium 6
• For torsades de pointes, administer 2g IV magnesium sulfate regardless of serum magnesium level 6
• Consider cardiology consultation for severe QTc prolongation 6