Does trazodone (an antidepressant medication) prolong the QT (quantitative electrocardiogram) interval?

From the Guidelines

Trazodone has a low risk of QT prolongation at standard therapeutic doses, but the risk increases at higher doses or when combined with other QT-prolonging medications. While trazodone can theoretically affect cardiac repolarization, significant QT prolongation is rare when the medication is used at typical antidepressant or sleep aid doses (50-300 mg daily) 1. However, the risk increases at higher doses, especially above 600 mg daily, or when combined with other QT-prolonging medications. Patients with pre-existing cardiac conditions, electrolyte abnormalities (particularly low potassium or magnesium), or those taking multiple QT-prolonging drugs should use trazodone with caution. The mechanism involves trazodone's mild inhibition of certain cardiac ion channels that affect ventricular repolarization. For most patients without cardiac risk factors, trazodone remains a relatively safe option compared to other antidepressants that have more significant effects on cardiac conduction. If you have heart problems or take other medications, consult your healthcare provider before starting trazodone.

Some key points to consider:

• Trazodone is not listed as a high-risk medication for QT prolongation in the guidelines, but it is still important to use caution when prescribing it to patients with cardiac risk factors 1.
• The risk of QT prolongation with trazodone is dose-dependent, and higher doses increase the risk of cardiac arrhythmias.
• Patients with pre-existing cardiac conditions, such as congenital long QT syndrome, should be closely monitored when taking trazodone.
• Electrolyte abnormalities, such as low potassium or magnesium, can increase the risk of QT prolongation with trazodone.
• Combining trazodone with other QT-prolonging medications can increase the risk of cardiac arrhythmias.

It is essential to weigh the benefits and risks of trazodone in individual patients and to monitor them closely for signs of QT prolongation or cardiac arrhythmias. If you have concerns about the safety of trazodone, consult your healthcare provider before starting the medication.

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). Concomitant administration of drugs may increase the risk of cardiac arrhythmia [see DRUG INTERACTIONS (7.1)]. 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. InterventionAvoid the use of Trazodone hydrochloride tablets in combination with other drugs known to prolongQTc[seeWARNINGS AND PRECAUTIONS(5. 3)].

Trazodone prolongs the QT/QTc interval. This is a direct effect of the medication, and it may increase the risk of cardiac arrhythmias, particularly when used in combination with other drugs that prolong the QT interval or in patients with preexisting cardiac disease 2, 2.

From the Research

Trazodone and QT Prolongation

• Trazodone has been associated with prolonged QT intervals and increased risk of polymorphous ventricular tachycardias in clinical settings 3, 4.
• A case study reported a 67-year-old female who developed trazodone-induced torsades de pointe (TdP) after taking 50 mg of trazodone daily for six days, with an initial electrocardiography (ECG) revealing a prolonged corrected QT interval (QTc = 586 ms) 3.
• In vitro studies have demonstrated that trazodone inhibits hERG (human ether-á-go-go-related gene) channel current, which can lead to QT prolongation 4.
• A study evaluating the effect of three single doses of trazodone on QTc interval in healthy subjects found a modest, dose-dependent effect on cardiac repolarization, with no QTc prolongation observed with the 20-mg dose and an effect exceeding the values set in E14 guideline with the 60- and 140-mg doses 5.
• Another case report described a young woman who developed significant QT prolongation and delayed atrioventricular nodal conduction after acute trazodone overdose, highlighting the importance of considering cardiotoxic effects after trazodone overdose 6.
• A comparative study of QT prolongation with serotonin reuptake inhibitors found that trazodone was not significantly associated with QT prolongation, unlike citalopram and escitalopram, which showed a clear signal of QT prolongation 7.

Mechanism of QT Prolongation

• Trazodone's inhibition of hERG channel current is thought to be the primary mechanism underlying its QT-prolonging effect 4.
• The drug's ability to inhibit hERG channel current at clinically relevant concentrations suggests that it may increase the risk of QT prolongation and associated arrhythmias 4.

Clinical Implications

• Close monitoring is essential to prevent adverse complications in trazodone users, particularly those with risk factors for QTc prolongation 3.
• Caution should be used when concomitantly using other medications that prolong QT or increase trazodone exposure 5.