What are the precautions for prescribing Trazodone (antidepressant) to older adults with a history of heart conditions due to the risk of QT (QT interval) prolongation?

Trazodone and QT Prolongation in Older Adults with Heart Disease

Direct Recommendation

Trazodone should be avoided in older adults with a history of cardiac arrhythmias, known QT prolongation, or other significant heart conditions due to documented risk of QTc prolongation and torsades de pointes, even at doses as low as 100 mg or less. 1

Absolute Contraindications

The FDA label explicitly states trazodone should be avoided in patients with: 1

• History of cardiac arrhythmias
• Known QT prolongation
• Symptomatic bradycardia
• Hypokalemia or hypomagnesemia
• Congenital long QT syndrome
• Acute myocardial infarction recovery phase

Cardiac Risk Profile

Trazodone prolongs the QT/QTc interval through its pharmacologic mechanism, and clinical studies demonstrate it may be arrhythmogenic in patients with preexisting cardiac disease. 1 Documented arrhythmias include isolated PVCs, ventricular couplets, tachycardia with syncope, and torsades de pointes at doses of 100 mg or less. 1

Recent case reports confirm fatal outcomes: a 67-year-old woman developed torsades de pointes on just 50 mg daily without traditional risk factors for QTc prolongation, requiring emergency defibrillation and temporary pacemaker placement. 2 Another case documented QTc prolongation to 586 ms following ingestion of 500 mg, requiring ICU admission. 3

Mandatory Pre-Treatment Assessment

Before prescribing trazodone to any older adult with cardiac history, obtain: 4

• Baseline ECG to measure QTc interval
• Complete medication review for other QT-prolonging drugs
• Electrolyte panel (potassium, magnesium, calcium)
• Cardiac history including arrhythmias, heart failure, ischemic disease

Drug Interactions Requiring Absolute Avoidance

The FDA label mandates avoiding trazodone in combination with: 1

• Class IA antiarrhythmics (quinidine, procainamide, disopyramide)
• Class III antiarrhythmics (amiodarone, sotalol, dofetilide) - one case report documented polymorphic ventricular tachycardia when trazodone was added to previously well-tolerated amiodarone 5
• CYP3A4 inhibitors (itraconazole, clarithromycin, voriconazole, ketoconazole) - these increase trazodone exposure and cardiac arrhythmia risk 1
• Certain antipsychotics (ziprasidone, chlorpromazine, thioridazine)
• Certain antibiotics (gatifloxacin, macrolides, fluoroquinolones) 6, 1

Safer Alternative Antidepressants for Cardiac Patients

When antidepressant therapy is needed in older adults with heart disease, consider: 6, 7

• SNRIs (duloxetine, venlafaxine) - registry studies show no association with cardiac arrest, though venlafaxine has cardiovascular adverse events that limit use 6, 7
• Selective SSRIs (sertraline, paroxetine, fluoxetine) - preferred over citalopram/escitalopram which have dose-dependent QTc prolongation 7
• Avoid tricyclic antidepressants - these carry the highest cardiac arrest risk (OR 1.69) and should not be used if PR or QTc interval is prolonged 6

Monitoring Protocol If Trazodone Must Be Used

If clinical circumstances absolutely require trazodone despite cardiac history (which should be rare), implement: 4

• Baseline ECG before initiation
• Repeat ECG at 2 weeks, then monthly 6
• Additional ECG after any dose increase 4
• Maintain potassium >4.0 mEq/L at all times 4
• Discontinue immediately if QTc >500 ms or increases >60 ms from baseline 4
• Consider cardiology consultation for QTc >500 ms 4

Critical Action Thresholds

Stop trazodone immediately if: 4, 7

• QTc exceeds 500 ms
• QTc increases >60 ms from baseline
• Development of T wave alternans, enhanced U waves, or polymorphic ventricular premature beats
• Any symptomatic arrhythmia occurs

Special Considerations for Older Adults

Age >65 years independently increases risk of drug-induced torsades de pointes. 4 Older patients are more likely to have: 6

• Multiple cardiac comorbidities
• Polypharmacy with potential drug interactions
• Baseline conduction abnormalities
• Electrolyte disturbances from diuretic therapy 4

The European Heart Journal guidelines specifically recommend starting tricyclic antidepressants at 10 mg/day in older patients due to cardiovascular risks, and this same caution should apply to trazodone. 6

Common Clinical Pitfall

Do not assume trazodone is "cardiac-safe" because it has minimal anticholinergic effects compared to tricyclics. 2, 8 While trazodone causes less orthostatic hypotension than most antidepressants and tends to lower heart rate, its QT-prolonging effects create significant arrhythmia risk in vulnerable cardiac patients. 8, 9 Historical data suggesting trazodone is safer in cardiac patients was based on studies using lower doses (100-300 mg) and excluding patients with ventricular irritability. 9