QT Prolongation Risk Assessed for Non-SSRI Antidepressants

the MPR take:

Although the Food and Drug Administration (FDA) requires drug companies to do extensive side-effect testing on their products prior to approval, including QT and QTc prolongation testing, there is still a concern that products that make it to market may cause QT prolongation, and subsequently torsades de pointes. In 2011, the labeling for the antidepressant citalopram, a selective serotonin reuptake inhibitor (SSRI), was updated to include a warning about the risk of QTc prolongation with higher doses. In a study published in the Annals of Pharmacotherapy, researchers reviewed data on newer nonselective serotonin reuptake inhibitor (non-SSRI) antidepressants to see assess their QT prolongation risk. After reviewing the literature, which was both ambiguous and insufficient, researchers concluded the following: 

  • For bupropion, QT prolongation is unlikely at normal doses; however, it did occur in overdose cases. Torsades de pointe was not reported in the literature. 
  • The risk of QT prolongation with desvenlafaxine appears to be low although data for this conclusion is lacking. 
  • Even at high doses, duloxetine does not appear to cause QT prolongation, although data is limited for patients with comorbidities. 
  • While the likelihood of QT prolongation with levomilnacipran is low, this assessment cannot be guaranteed due to insufficient data.
  •  Mirtazapine probably poses low risk, although one study did show an increased risk of SCD/VA (cardiovascular risk for sudden death and ventricular arrhythmias) in patients with chronic illnesses.
  •  Vilazodone is unlikely to prolong the QT interval based on one clinical trial. 
  • Out of all the studied drugs, venlafaxine appears to have the greatest risk, particularly among elderly patients, for prolonging the QT interval.

While routine ECG monitoring is unnecessary, for those with risk factors for QT prolongation, the authors suggest choosing another agent. The authors stress that due to shorter market life span, the conclusions presented in the study cannot be guaranteed and data in patients with comorbities is limited.

QT Prolongation Risk Assessed for Non-SSRI Antidepressants
QT Prolongation Risk Assessed for 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. 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.



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