What are the cardiac side effects of Trazodone (triazolopyridine antidepressant)?

From the Guidelines

Trazodone can cause several cardiac side effects, including orthostatic hypotension, QT interval prolongation, tachycardia, and arrhythmias, and its use should be cautious in patients with pre-existing heart conditions or those taking other medications that affect heart rhythm. The most common cardiac side effect is orthostatic hypotension, which causes dizziness or lightheadedness when standing up quickly. Trazodone may also cause QT interval prolongation, which can potentially lead to dangerous heart rhythm disturbances, particularly in patients with pre-existing heart conditions or those taking other medications that affect heart rhythm. Some patients may experience tachycardia (rapid heart rate) or palpitations while taking this medication. Rarely, trazodone has been associated with arrhythmias and cardiac conduction abnormalities, including atrial fibrillation, as reported in a recent narrative review of drug-induced atrial fibrillation 1. These cardiac effects occur because trazodone blocks alpha-adrenergic receptors, affecting blood vessel tone and blood pressure regulation, and can influence cardiac ion channels. Patients with pre-existing heart disease, electrolyte abnormalities, or those taking other medications that affect heart function should use trazodone cautiously. The risk of cardiac side effects is generally dose-dependent, with higher doses increasing the likelihood of adverse effects. If experiencing chest pain, irregular heartbeat, severe dizziness, or fainting while taking trazodone, medical attention should be sought immediately.

Some key points to consider when prescribing trazodone include:

• Monitoring for signs of orthostatic hypotension, such as dizziness or lightheadedness, especially when standing up quickly
• Assessing the risk of QT interval prolongation, particularly in patients with pre-existing heart conditions or those taking other medications that affect heart rhythm
• Being aware of the potential for tachycardia, palpitations, and arrhythmias, including atrial fibrillation
• Using caution when prescribing trazodone to patients with pre-existing heart disease, electrolyte abnormalities, or those taking other medications that affect heart function
• Educating patients on the importance of seeking medical attention immediately if they experience chest pain, irregular heartbeat, severe dizziness, or fainting while taking trazodone.

It is essential to weigh the benefits of trazodone against the potential cardiac risks, and to consider alternative treatments if necessary, as suggested by a study on the treatment of depressive disorders 1. However, the most recent and highest quality study on the topic of drug-induced atrial fibrillation 1 should be prioritized when making a definitive recommendation.

From the FDA Drug Label

Clinical studies indicate that trazodone hydrochloride may be arrhythmogenic in patients with preexisting cardiac disease. Arrhythmias identified include isolated PVCs, ventricular couplets, tachycardia with syncope, and torsade de pointes Trazodone Hydrochloride Tablets prolongs the QT/QTc interval. Trazodone Hydrochloride Tablets should also be avoided in patients with a history of cardiac arrhythmias, as well as other circumstances that may increase the risk of the occurrence of torsade de pointes and/or sudden death, including symptomatic bradycardia, hypokalemia or hypomagnesemia, and the presence of congenital prolongation of the QT interval

Cardiac Side Effects of Trazodone:

• Trazodone may cause cardiac arrhythmias, including isolated PVCs, ventricular couplets, tachycardia with syncope, and torsade de pointes, especially in patients with preexisting cardiac disease.
• Trazodone prolongs the QT/QTc interval, which may increase the risk of cardiac arrhythmias.
• Patients with a history of cardiac arrhythmias, symptomatic bradycardia, hypokalemia or hypomagnesemia, and congenital prolongation of the QT interval should avoid taking Trazodone or be closely monitored. 2 2

From the Research

Trazodone Cardiac Side Effects

• Trazodone is hypothesized to be less cardiotoxic than tri-tetracyclic antidepressants 3
• It has little effect on cardiac conduction and does not worsen supraventricular arrhythmias 3
• Trazodone produces less postural hypotension than most other antidepressants and tends to lower heart rate 3
• Lower doses of trazodone (100-300 mg) are better tolerated and more effective in major depressives simultaneously debilitated by significant cardiovascular disease 3
• Trazodone has few cardiovascular side effects, and in patients ingesting toxic amounts, no deaths have been reported unless other drugs were present or ingested concomitantly 4
• However, trazodone may be associated infrequently with orthostatic hypotension, QT interval prolongation, cardiac arrhythmias, and rare episodes of priapism 5
• A case report describes a young woman who developed significant QT prolongation and delayed atrioventricular nodal conduction after acute trazodone overdose 6
• The incidences of both anticholinergic and cardiovascular effects were notably lower in elderly patients treated with trazodone compared with older tricyclic antidepressants 7
• Trazodone is relatively safe in overdose, with no deaths reported unless other drugs were present or ingested concomitantly 4, 7