Can trazodone increase heart rate, particularly in patients with pre-existing cardiovascular disease or cardiovascular risk factors?

Can Trazodone Increase Heart Rate?

Trazodone typically decreases heart rate rather than increasing it, but can paradoxically cause tachycardia as part of serotonin syndrome or in the context of cardiac arrhythmias, particularly in patients with pre-existing cardiovascular disease. 1

Primary Cardiovascular Effects

Trazodone's predominant cardiovascular effect is heart rate reduction, not elevation. Clinical pharmacology studies demonstrate that trazodone significantly decreases heart rate through its alpha-receptor blocking activity 2. In healthy subjects, trazodone (150 mg) decreased both heart rate and blood pressure at 90 minutes post-dosing 2.

When Tachycardia Can Occur

Serotonin Syndrome

Tachycardia is a cardinal feature of serotonin syndrome, a potentially life-threatening condition that can occur with trazodone. The FDA label explicitly warns that serotonin syndrome presents with autonomic instability including tachycardia, labile blood pressure, diaphoresis, flushing, and hyperthermia 1. This risk is substantially increased when trazodone is combined with:

• Other serotonergic drugs (SSRIs, SNRIs, triptans, tramadol, fentanyl, lithium) 1
• MAO inhibitors (contraindicated combination) 1

Cardiac Arrhythmias

Trazodone can be arrhythmogenic in patients with pre-existing cardiac disease, causing various tachyarrhythmias. The FDA label states that clinical studies indicate trazodone may cause arrhythmias including ventricular tachycardia with syncope and torsade de pointes 1. Identified arrhythmias include:

• Isolated premature ventricular contractions (PVCs)
• Ventricular couplets
• Ventricular tachycardia 1, 3
• Torsade de pointes (reported at doses ≤100 mg) 1

High-Risk Patient Populations

Exercise extreme caution in patients with cardiovascular risk factors or pre-existing cardiac disease. The FDA label specifically warns that trazodone should be avoided in patients with 1:

• History of cardiac arrhythmias
• Known QT prolongation
• Symptomatic bradycardia (paradoxically increases arrhythmia risk)
• Hypokalemia or hypomagnesemia
• Congenital long QT syndrome
• Recent myocardial infarction (not recommended during initial recovery phase)

Patients with pre-existing ventricular irritability may experience worsening arrhythmias. Case reports document increased ventricular premature beats and repetitive forms after starting trazodone in patients with baseline ventricular irritability 4. One case report described life-threatening ventricular tachycardia in a patient without prior cardiovascular disease 3.

Drug Interactions That Increase Tachycardia Risk

Avoid combining trazodone with QT-prolonging medications, as this increases arrhythmia risk. The FDA label explicitly states trazodone should be avoided with 1:

• Class 1A antiarrhythmics (quinidine, procainamide)
• Class 3 antiarrhythmics (amiodarone, sotalol)
• Certain antipsychotics (ziprasidone, chlorpromazine, thioridazine)
• Strong CYP3A4 inhibitors (itraconazole, clarithromycin, voriconazole)

Isolated cases of drug-induced atrial fibrillation have been reported with trazodone, particularly in patients without previous heart disease 5.

Clinical Monitoring Recommendations

Close cardiac monitoring is essential when prescribing trazodone to patients with cardiac disease. The FDA label recommends 1:

• Baseline ECG assessment in high-risk patients
• Monitoring for signs of arrhythmias during treatment
• Lower starting doses (100-300 mg) in patients with significant cardiovascular disease 4
• Immediate discontinuation if tachyarrhythmias develop

In severe overdose, multiple cardiac complications can occur sequentially. A case report documented QTc prolongation evolving into ventricular tachycardia, followed by bundle branch blocks and AV nodal blocks occurring 12-24 hours post-ingestion 6.

Critical Pitfalls to Avoid

• Do not assume trazodone is "cardiac-safe" simply because it lacks anticholinergic effects - it carries distinct arrhythmia risks, particularly QT prolongation and ventricular arrhythmias 1, 6
• Do not overlook the paradox that baseline bradycardia increases arrhythmia risk with trazodone, despite the drug typically lowering heart rate 1
• Do not combine with other QT-prolonging agents without careful risk-benefit assessment 1
• Do not ignore new-onset palpitations or syncope in patients taking trazodone, as these may herald serious arrhythmias 1