Trazodone Safety in Atrial Fibrillation
Trazodone should be avoided in patients with atrial fibrillation due to significant arrhythmogenic risk, including documented cases of ventricular tachycardia, QT prolongation, and torsade de pointes, particularly in patients with preexisting cardiac disease. 1
Primary Safety Concerns
The FDA label explicitly warns that trazodone is arrhythmogenic in patients with preexisting cardiac disease, which includes atrial fibrillation 1. Key cardiac risks include:
- Ventricular arrhythmias: Isolated PVCs, ventricular couplets, ventricular tachycardia with syncope, and torsade de pointes have been documented 1
- QT prolongation: Trazodone prolongs the QT/QTc interval, with post-marketing reports of torsade de pointes occurring at doses as low as 100 mg or less 1
- Multiple conduction abnormalities: Case reports document progression from QTc prolongation to ventricular tachycardia, right bundle-branch block, left anterior fascicular block, and variable degrees of AV nodal blocks 2
Specific Contraindications in AFib Patients
Trazodone should be avoided in patients with:
- History of cardiac arrhythmias (including atrial fibrillation) 1
- Symptomatic bradycardia 1
- Known QT prolongation 1
- Conditions increasing torsade de pointes risk 1
Critical Drug Interactions
The risk is substantially amplified when trazodone is combined with:
- Class IA antiarrhythmics (quinidine, procainamide) - commonly used in AFib rhythm control 1
- Class III antiarrhythmics (amiodarone, sotalol) - first-line agents for AFib with heart failure or structural disease 3, 4, 1
- CYP3A4 inhibitors (clarithromycin, itraconazole, voriconazole) which increase trazodone levels 1
This creates a particularly dangerous scenario since amiodarone and sotalol are guideline-recommended first-line agents for AFib patients with heart failure or coronary disease 3, 4. One case report documented trazodone-induced parkinsonism likely exacerbated by concurrent amiodarone use, which inhibited trazodone metabolism 5.
Clinical Evidence of Harm
- A 45-year-old man with no prior cardiovascular disease developed life-threatening premature ventricular contractions and angina after starting trazodone 6
- Two patients with preexisting ventricular irritability showed increased ventricular premature beats and repetitive forms after trazodone initiation 7
- A 55-year-old woman developed QTc prolongation evolving into ventricular tachycardia, multiple conduction blocks, seizures, cardiogenic shock, and respiratory arrest 12-24 hours after trazodone overdose 2
Alternative Approaches
For insomnia in AFib patients, consider:
- Non-pharmacologic interventions (sleep hygiene, cognitive behavioral therapy)
- Melatonin or melatonin receptor agonists
- Low-dose doxepin (which has less cardiac toxicity than trazodone)
- Consultation with cardiology before initiating any sedative-hypnotic in patients with active arrhythmias
Common Pitfall
The most dangerous misconception is that trazodone is "cardiac-safe" because it lacks anticholinergic effects of tricyclic antidepressants 2. While trazodone may have less effect on cardiac conduction than tricyclics at therapeutic doses 7, it carries distinct and serious arrhythmogenic risks that are particularly hazardous in patients with preexisting arrhythmias like atrial fibrillation 1, 6.
If trazodone must be used despite AFib (which is not recommended), mandatory precautions include:
- Baseline and serial ECG monitoring for QTc interval 1
- Review all concurrent medications for QT-prolonging agents and drug interactions 1
- Use lowest effective dose (though toxicity reported even at 100 mg) 1
- Close cardiac monitoring, particularly during the first 24-36 hours when arrhythmias are most likely 2