From the Guidelines
Trazodone can cause QT interval prolongation, particularly at higher doses or in patients with pre-existing cardiac conditions or electrolyte abnormalities. The risk of QT interval prolongation with trazodone is generally considered low at standard therapeutic doses, typically used for depression (50-300 mg/day) or insomnia (25-100 mg) 1. However, the risk increases with higher doses, especially above 300 mg daily. Some key points to consider:
- Trazodone affects cardiac ion channels, particularly potassium channels, which alters cardiac repolarization and can lead to QT prolongation 1.
- Patients with pre-existing cardiac conditions, electrolyte abnormalities (particularly low potassium or magnesium), or those taking other QT-prolonging medications may be at greater risk of QT prolongation with trazodone 1.
- Clinicians should consider obtaining baseline and follow-up ECGs in high-risk patients, especially when using higher doses of trazodone 1.
- Symptoms of concerning QT prolongation may include palpitations, dizziness, or syncope, which should prompt immediate medical evaluation 1.
- If QT prolongation is a significant concern for a patient, alternative medications with even lower risk profiles might be considered 1.
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 key warning in the drug label, and it is essential to be aware of this potential risk when prescribing or taking trazodone. The label advises avoiding the use of trazodone in combination with other drugs known to prolong the QTc interval, as this may increase the risk of cardiac arrhythmia 2 2.
From the Research
Trazodone and QT Interval Prolongation
- Trazodone, an antidepressant medication, has been associated with QT interval prolongation in several studies 3, 4, 5, 6.
- A case report published in 2024 described a 67-year-old female who developed trazodone-induced torsades de pointe (TdP) with a prolonged corrected QT interval (QTc = 586 ms) after taking 50 mg of trazodone daily for six days 3.
- Another study published in 1995 reported a case of QT prolongation and polymorphous ventricular tachycardia associated with the combination of trazodone and amiodarone 4.
- In vitro studies have shown that trazodone inhibits hERG channel current, which can lead to QT interval prolongation 5.
- A case report published in 2023 described a 45-year-old female who presented with hypotension and QTc prolongation after ingesting five 100 mg trazodone tablets 6.
- A study published in 2020 evaluated the effect of three single doses of trazodone on the QTc interval in healthy subjects and 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 7.
Key Findings
- Trazodone can cause QT interval prolongation, particularly at higher doses 3, 5, 6, 7.
- The risk of QT interval prolongation is increased when trazodone is combined with other medications that prolong QT or increase trazodone exposure 4, 7.
- Close monitoring is essential to prevent adverse complications in trazodone users, particularly those with a history of cardiovascular disease or those taking other medications that can affect the QT interval 3, 6.