Does trazodone (an antidepressant medication) cause QT interval prolongation?

From the Guidelines

Trazodone is considered to have a low risk of QT interval prolongation at standard therapeutic doses, but the risk may increase at higher doses, in overdose situations, or when combined with other QT-prolonging medications. While trazodone can theoretically affect cardiac repolarization, significant QT prolongation is uncommon with this medication when used at typical antidepressant or sleep aid doses (50-300 mg daily) 1. However, patients with pre-existing cardiac conditions, electrolyte abnormalities (especially low potassium or magnesium), or those taking multiple QT-prolonging drugs should be monitored more carefully. Trazodone works primarily as a serotonin antagonist and reuptake inhibitor, and its cardiac effects are generally mild compared to other antidepressants like tricyclics.

Some key points to consider when evaluating the risk of QT prolongation with trazodone include:

• The risk of QT prolongation increases with dose and plasma drug concentration, although the exact incidence of QT prolongation with trazodone is not well established 1
• Trazodone is not listed as a high-risk medication for QT prolongation in the guidelines, but it is mentioned as a potential cause of torsades de pointes in patients with purposeful overdose 1
• The Arizona Center for Education & Research on Therapeutics maintains an updated list of drugs that have a risk of causing torsades de pointes, including trazodone, but notes that the risk is generally low 1
• The ACC/AHA/ESC 2006 guidelines for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death recommend removal of the offending agent in patients with drug-induced long QT syndrome, but do not specifically mention trazodone as a high-risk medication 1

For most patients without cardiac risk factors, trazodone is considered a relatively safe option with minimal QT concerns at standard doses. However, careful monitoring and consideration of the potential risks and benefits are necessary when prescribing trazodone, especially in patients with pre-existing cardiac conditions or those taking other QT-prolonging medications.

From the FDA Drug Label

Trazodone Hydrochloride Tablets prolongs the QT/QTc interval. The use of Trazodone Hydrochloride Tablets should be avoided in patients with known QT prolongation or in combination with other drugs that are inhibitors of CYP3A4 (e.g., itraconazole, clarithromycin, voriconazole), or known to prolong QT interval including Class 1A antiarrhythmics (e.g., quinidine, procainamide) or Class 3 antiarrhythmics (e.g., amiodarone, sotalol), certain antipsychotic medications (e.g., ziprasidone, chlorpromazine, thioridazine), and certain antibiotics (e.g., gatifloxacin). QTIntervalProlongation ClinicalImpact:Concomitant use of drugs that prolong the QT interval may add to the QT effects of Trazodone hydrochloride tablets and increase the risk of cardiac arrhythmia.

Trazodone causes QT interval prolongation. This is a direct effect of the medication, and it may increase the risk of cardiac arrhythmia, particularly when used in combination with other drugs that prolong the QT interval 2, 2.

From the Research

Trazodone and QT Interval Prolongation

• Trazodone, an antidepressant medication, has been associated with QT interval prolongation, which can lead to polymorphic ventricular tachycardia, known as torsades de pointes (TdP) 3, 4.
• Studies have shown that trazodone can inhibit the hERG (human ether-á-go-go-related gene) channel current, which can lead to QT interval prolongation 5.
• The risk of QT interval prolongation and TdP is not limited to patients with pre-existing risk factors, and close monitoring is essential to prevent adverse complications in trazodone users 3, 4.
• Other psychotropic medications, including antidepressants and antipsychotics, have also been associated with QT interval prolongation, highlighting the importance of careful monitoring and individualized risk assessment 6, 7.

Clinical Implications

• Trazodone-induced QT interval prolongation can be fatal, even in patients without pre-existing risk factors 3, 4.
• Close monitoring of patients taking trazodone, including regular ECGs and monitoring for signs of QT interval prolongation, is crucial to prevent adverse complications 3, 4.
• The frequency of cardiac monitoring for patients receiving psychiatric medications, including trazodone, should be individually determined based on the prescribed agent and additional risk factors for TdP 7.

Mechanism of Action

• Trazodone's inhibition of the hERG channel current is thought to be the primary mechanism by which it prolongs the QT interval 5.
• The effects of trazodone on the QT interval are similar to those of other agents known to inhibit the hERG channel current, such as astemizole, terfenadine, and cisapride 5.