Trazodone and QT Prolongation
Yes, trazodone definitively causes QT interval prolongation and carries a risk of torsades de pointes, even at therapeutic doses as low as 100 mg or less. 1
FDA Black Box Warning and Cardiac Risk Profile
The FDA drug label explicitly states that trazodone prolongs the QT/QTc interval and should be avoided in patients with known QT prolongation 1. Key cardiac risks include:
- Trazodone is arrhythmogenic in patients with preexisting cardiac disease, with documented cases of isolated PVCs, ventricular couplets, ventricular tachycardia with syncope, and torsades de pointes 1
- Post-marketing reports confirm torsades de pointes occurring at doses of 100 mg or less with immediate-release formulations 1
- The mechanism involves direct inhibition of hERG (human ether-á-go-go-related gene) potassium channels with an IC50 of 0.69 μM, occurring at clinically relevant concentrations 2
High-Risk Patient Populations to Avoid
Trazodone should be avoided entirely in patients with: 1
- History of cardiac arrhythmias
- Symptomatic bradycardia
- Hypokalemia or hypomagnesemia
- Congenital long QT syndrome
- Acute myocardial infarction (initial recovery phase)
- Concomitant use of other QT-prolonging medications (Class 1A antiarrhythmics like quinidine/procainamide, Class 3 antiarrhythmics like amiodarone/sotalol, antipsychotics like ziprasidone/chlorpromazine/thioridazine, or antibiotics like gatifloxacin) 1
Drug Interactions That Amplify Risk
Avoid combining trazodone with: 1
- Strong CYP3A4 inhibitors (itraconazole, ketoconazole, clarithromycin, indinavir) - these increase trazodone exposure and amplify cardiac arrhythmia risk; if unavoidable, use a lower trazodone dose 1
- Other QT-prolonging medications - the American Heart Association notes trazodone has been implicated in torsades de pointes when combined with other QT-prolonging drugs 3
- One case report documented marked QT prolongation and polymorphous ventricular tachycardia when trazodone was added to previously well-tolerated amiodarone therapy 4
Clinical Evidence of Real-World Harm
Recent case reports demonstrate trazodone's cardiac toxicity:
- A 67-year-old woman on 50 mg daily trazodone developed QTc of 586 ms and torsades de pointes requiring defibrillation and temporary pacemaker, despite having no other risk factors for QT prolongation 5
- A 45-year-old woman who ingested 500 mg trazodone developed progressive QTc prolongation from 502 ms to 586 ms with hypotension requiring ICU admission 6
- In a poison center study of 760 exposures, trazodone had a statistically significant association with QTc >500 ms, though life-threatening dysrhythmias were rare (0.8%) 7
Monitoring Requirements If Trazodone Must Be Used
If trazodone cannot be avoided, implement the following protocol: 8, 1
- Obtain baseline ECG before initiating therapy and correct all electrolyte abnormalities (potassium, magnesium, calcium) 8
- Repeat ECG 7 days after starting therapy and after any dose change 8
- Discontinue trazodone immediately if QTc exceeds 500 ms or increases >60 ms from baseline 8
- Monitor patients closely for cardiac symptoms including syncope, palpitations, or dizziness 1
- Maintain serum potassium between 4.5-5 mEq/L to reduce arrhythmia risk 8
Comparison to Safer Alternatives
Unlike benzodiazepines, which carry no QT prolongation risk, trazodone poses definite cardiac hazards 3. When treating insomnia or depression in patients with cardiac risk factors, consider alternatives without QT effects rather than implementing complex monitoring protocols for a medication with documented fatal outcomes.