Christopher Kogut1, Ericka Breden Crouse2, W Victor R Vieweg3, Mehrul Hasnain4, Adrian Baranchuk5, Geneviève C Digby5, Jayanthi N Koneru6, Antony Fernandez7, Anand Deshmukh8, Jules C Hancox9, Ananda K Pandurangi1. 1. Department of Psychiatry, Virginia Commonwealth University, Richmond, VA, USA. 2. Department of Pharmacy, Virginia Commonwealth University, Richmond, VA, USA. 3. Departments of Psychiatry and Internal Medicine, Virginia Commonwealth University, 17 Runswick Drive, Richmond, VA 23238-5414, USA. 4. Department of Psychiatry, Memorial University, St John's, Newfoundland, Canada. 5. Department of Cardiology, Kingston General Hospital, Queen's University, Kingston, Ontario, Canada. 6. Department of Internal Medicine, Division of Cardiology and Cardiac Electrophysiology, Virginia Commonwealth University, Richmond, VA, USA. 7. Department of Psychiatry, Virginia Commonwealth University, and Psychiatry Service, Hunter Holmes McGuire Veterans Affairs Medical Center, Richmond, VA, USA. 8. Department of Cardiovascular Medicine, The Cardiac Center of Creighton University, Omaha, NE, USA. 9. School of Physiology and Pharmacology and Cardiovascular Research Laboratories, Medical Sciences Building, University of Bristol, University Walk, Bristol BS8 1TD, UK.
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? 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.
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.
Entities:
Keywords:
QTc interval prolongation; SSRIs; antidepressant drugs; torsade de pointes
Authors: P Weeke; A Jensen; F Folke; G H Gislason; J B Olesen; C Andersson; E L Fosbøl; J K Larsen; F K Lippert; S L Nielsen; T Gerds; P K Andersen; J K Kanters; H E Poulsen; S Pehrson; L Køber; C Torp-Pedersen Journal: Clin Pharmacol Ther Date: 2012-05-16 Impact factor: 6.875
Authors: Michael E Henry; Mark E Schmidt; John Hennen; Rosemond A Villafuerte; Michelle L Butman; Pierre Tran; Lynn T Kerner; Bruce Cohen; Perry F Renshaw Journal: Neuropsychopharmacology Date: 2005-08 Impact factor: 7.853
Authors: S Rajamani; L L Eckhardt; C R Valdivia; C A Klemens; B M Gillman; C L Anderson; K M Holzem; B P Delisle; B D Anson; J C Makielski; C T January Journal: Br J Pharmacol Date: 2006-09-11 Impact factor: 8.739
Authors: Bryan D Hayes; Wendy Klein-Schwartz; Richard F Clark; Allison A Muller; Jane E Miloradovich Journal: J Emerg Med Date: 2008-12-11 Impact factor: 1.484
Authors: Mar Carceller-Sindreu; Javier de Diego-Adeliño; Maria J Portella; Xavier Garcia-Moll; Maria Figueras; Aina Fernandez-Vidal; Josep M Queraltó; Dolors Puigdemont; Enric Álvarez Journal: Eur Arch Psychiatry Clin Neurosci Date: 2017-01-23 Impact factor: 5.270
Authors: M Nosè; I Bighelli; M Castellazzi; G Martinotti; G Carrà; C Lucii; G Ostuzzi; F Sozzi; C Barbui Journal: Epidemiol Psychiatr Sci Date: 2015-10-15 Impact factor: 6.892
Authors: W Victor R Vieweg; Mehrul Hasnain; Jules C Hancox; Adrian Baranchuk; Geneviève C Digby; Christopher Kogut; Ericka L Breden Crouse; Jayanthi N Koneru; Anand Deshmukh; Ananda K Pandurangi Journal: Psychopharmacology (Berl) Date: 2013-06-30 Impact factor: 4.530
Authors: W Victor R Vieweg; Jules C Hancox; Mehrul Hasnain; Jayanthi N Koneru; Michael Gysel; Adrian Baranchuk Journal: Ther Adv Infect Dis Date: 2013-08
Authors: Mohammad Hassan Nezafati; Ali Eshraghi; Mohammad Vojdanparast; Saeed Abtahi; Pouya Nezafati Journal: J Res Med Sci Date: 2016-09-01 Impact factor: 1.852
Authors: Jules C Hancox; Mehrul Hasnain; W Victor R Vieweg; Michael Gysel; Michelle Methot; Adrian Baranchuk Journal: Ther Adv Infect Dis Date: 2014-04