title: Antipsychotics and torsadogenic risk: signals emerging from the US FDA Adverse Event Reporting System database.
abstract: BACKGROUND
  Drug-induced torsades de pointes (TdP) and related clinical entities represent a current regulatory and clinical burden.
  
  
  OBJECTIVE
  As part of the FP7 ARITMO (Arrhythmogenic Potential of Drugs) project, we explored the publicly available US FDA Adverse Event Reporting System (FAERS) database to detect signals of torsadogenicity for antipsychotics (APs).
  
  
  METHODS
  Four groups of events in decreasing order of drug-attributable risk were identified: (1) TdP, (2) QT-interval abnormalities, (3) ventricular fibrillation/tachycardia, and (4) sudden cardiac death. The reporting odds ratio (ROR) with 95 % confidence interval (CI) was calculated through a cumulative analysis from group 1 to 4. For groups 1+2, ROR was adjusted for age, gender, and concomitant drugs (e.g., antiarrhythmics) and stratified for AZCERT drugs, lists I and II (http://www.azcert.org , as of June 2011). A potential signal of torsadogenicity was defined if a drug met all the following criteria: (a) four or more cases in group 1+2; (b) significant ROR in group 1+2 that persists through the cumulative approach; (c) significant adjusted ROR for group 1+2 in the stratum without AZCERT drugs; (d) not included in AZCERT lists (as of June 2011).
  
  
  RESULTS
  Over the 7-year period, 37 APs were reported in 4,794 cases of arrhythmia: 140 (group 1), 883 (group 2), 1,651 (group 3), and 2,120 (group 4). Based on our criteria, the following potential signals of torsadogenicity were found: amisulpride (25 cases; adjusted ROR in the stratum without AZCERT drugs = 43.94, 95 % CI 22.82-84.60), cyamemazine (11; 15.48, 6.87-34.91), and olanzapine (189; 7.74, 6.45-9.30).
  
  
  CONCLUSIONS
  This pharmacovigilance analysis on the FAERS found 3 potential signals of torsadogenicity for drugs previously unknown for this risk.
authors.affiliation: Department of Medical and Surgical Sciences, Pharmacology Unit, Alma Mater Studiorum, University of Bologna, Via Irnerio 48, 40126 Bologna, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Poluzzi
authors.forename: Emanuel
authors.initials: E
authors.lastname: Raschi
authors.forename: Ariola
authors.initials: A
authors.lastname: Koci
authors.forename: Ugo
authors.initials: U
authors.lastname: Moretti
authors.forename: Edoardo
authors.initials: E
authors.lastname: Spina
authors.forename: Elijah R
authors.initials: ER
authors.lastname: Behr
authors.forename: Miriam
authors.initials: M
authors.lastname: Sturkenboom
authors.forename: Fabrizio
authors.initials: F
authors.lastname: De Ponti
mesh_terms: D016907:Adverse Drug Reaction Reporting Systems; D000077582:Amisulpride; D014150:Antipsychotic Agents / Q000009:adverse effects*; D001145:Arrhythmias, Cardiac / Q000139:chemically induced / Q000453:epidemiology; D001569:Benzodiazepines / Q000009:adverse effects; D054715:Cardiotoxins / Q000009:adverse effects; D002317:Cardiovascular Agents / Q000009:adverse effects*; D062313:Databases, Pharmaceutical; D016757:Death, Sudden, Cardiac / Q000453:epidemiology / Q000209:etiology; D005260:Female; D006801:Humans; D008297:Male; D000077152:Olanzapine; D010640:Phenothiazines / Q000009:adverse effects; D012306:Risk; D013469:Sulpiride / Q000009:adverse effects / Q000031:analogs & derivatives; D013610:Tachycardia / Q000139:chemically induced / Q000453:epidemiology; D016171:Torsades de Pointes / Q000139:chemically induced* / Q000453:epidemiology; D014481:United States; D014486:United States Food and Drug Administration; D014693:Ventricular Fibrillation / Q000139:chemically induced / Q000453:epidemiology
chemical_list: D014150:Antipsychotic Agents; D054715:Cardiotoxins; D002317:Cardiovascular Agents; D010640:Phenothiazines; D001569:Benzodiazepines; D013469:Sulpiride; D000077582:Amisulpride; C028457:cyamemazine; D000077152:Olanzapine
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