title: Selective serotonin reuptake inhibitors and torsade de pointes: new concepts and new directions derived from a systematic review of case reports.
abstract: 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?
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Psychiatry, Virginia Commonwealth University, Richmond, VA, USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: Kogut
authors.affiliation: Department of Pharmacy, Virginia Commonwealth University, Richmond, VA, USA.
authors.forename: Ericka Breden
authors.initials: EB
authors.lastname: Crouse
authors.affiliation: Departments of Psychiatry and Internal Medicine, Virginia Commonwealth University, 17 Runswick Drive, Richmond, VA 23238-5414, USA.
authors.forename: W Victor R
authors.initials: WV
authors.lastname: Vieweg
authors.affiliation: Department of Psychiatry, Memorial University, St John's, Newfoundland, Canada.
authors.forename: Mehrul
authors.initials: M
authors.lastname: Hasnain
authors.affiliation: Department of Cardiology, Kingston General Hospital, Queen's University, Kingston, Ontario, Canada.
authors.forename: Adrian
authors.initials: A
authors.lastname: Baranchuk
authors.affiliation: Department of Cardiology, Kingston General Hospital, Queen's University, Kingston, Ontario, Canada.
authors.forename: Geneviève C
authors.initials: GC
authors.lastname: Digby
authors.affiliation: Department of Internal Medicine, Division of Cardiology and Cardiac Electrophysiology, Virginia Commonwealth University, Richmond, VA, USA.
authors.forename: Jayanthi N
authors.initials: JN
authors.lastname: Koneru
authors.affiliation: Department of Psychiatry, Virginia Commonwealth University, and Psychiatry Service, Hunter Holmes McGuire Veterans Affairs Medical Center, Richmond, VA, USA.
authors.forename: Antony
authors.initials: A
authors.lastname: Fernandez
authors.affiliation: Department of Cardiovascular Medicine, The Cardiac Center of Creighton University, Omaha, NE, USA.
authors.forename: Anand
authors.initials: A
authors.lastname: Deshmukh
authors.affiliation: School of Physiology and Pharmacology and Cardiovascular Research Laboratories, Medical Sciences Building, University of Bristol, University Walk, Bristol BS8 1TD, UK.
authors.forename: Jules C
authors.initials: JC
authors.lastname: Hancox
authors.affiliation: Department of Psychiatry, Virginia Commonwealth University, Richmond, VA, USA.
authors.forename: Ananda K
authors.initials: AK
authors.lastname: Pandurangi
keywords: QTc interval prolongation; SSRIs; antidepressant drugs; torsade de pointes
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