Risk of QT/QTc prolongation among newer non-SSRI antidepressants

Objective: To review QT prolongation potential with newer nonselective serotonin reuptake inhibitor (non-SSRI) antidepressants.

Data sources: A PubMed literature search was performed from 1982 through June 16, 2014. Search terms included bupropion, desvenlafaxine, duloxetine, levomilnacipran, mirtazapine, venlafaxine, and vilazodone in combination with each of the following terms: cardiac toxicity, QTc prolongation, QT prolongation, torsades de pointes, and TdP.

Study selection and data extraction: English-language human studies, case reports, package inserts, manufacturer electronic communications, and ArizonaCert database were utilized.

Data synthesis: Rare QT prolongation has been reported with venlafaxine at therapeutic doses and in overdose. Bupropion has also been linked to QT prolongation in overdose situations. In elderly patients with a variety of high-risk comorbidities, mirtazapine did demonstrate higher odds of sudden cardiac death and ventricular arrhythmias when compared with paroxetine. Largely because of a lack of available data, existing studies fail to demonstrate QT prolongation with desvenlafaxine, duloxetine, levomilnacipran, and vilazodone.

Conclusion: Based on the current literature, risk of QT/QTc prolongation with the majority of newer non-SSRI antidepressants at therapeutic doses is low. The highest risk for QT prolongation appears to exist in overdose situations with venlafaxine and bupropion. Given the few to nonexistent controlled studies and confounding variables present in case reports, it is difficult to draw conclusions on QT prolongation risk with many of the newer non-SSRI antidepressants.