Selective serotonin reuptake inhibitors and torsade de pointes: new concepts and new directions derived from a systematic review of case reports

OBJECTIVE: In the light of the recent United States Food and Drug Administration (FDA) warning to clinicians on using previously approved doses of citalopram because of the purported higher risk of torsade de pointes (TdP), we pursued the broader question: are selective serotonin reuptake inhibitor (SSRI) antidepressant agents as a group unsafe because they might induce QTc interval prolongation and TdP?

METHOD: We reviewed the literature and found only 15 case reports (6 of fluoxetine, 1 of sertraline and 8 of citalopram) of SSRI-associated QTc interval prolongation linking to TdP.

RESULTS: A total of 13 cases contained sufficient information for analysis. In the setting of TdP, QTc interval prolongation does not clearly relate to SSRI dose.

CONCLUSION: Applying conventional statistics as the FDA does may not be the best tool to study this phenomenon because SSRI-associated TdP is a very rare event and hence best understood as an 'extreme outlier'. Despite the limitations inherent in case report material, case reports on drug-associated QTc interval prolongation and TdP provide valuable information that should be considered along with other sources of information for clinical guidance.