Risk excess of mortality and use of antipsychotics: a case-noncase study.
Severe mental disorders are associated with an increased mortality risk and the use of antipsychotic drugs may be one of the causes. In this study, we addressed the potential association of the reported mortality among patients on antipsychotics compared to other drugs from a pharmacovigilance database with the aim of evaluating the drug-induced mortality risk. A database containing 189 441 entries of suspected adverse reactions reported from 1 January 1995 to 31 December 2012 was explored for fatal outcomes. Potential disproportionality was estimated using the reporting odds ratio, proportional reporting ratio, and the χ-test. Two-hundred fatal outcomes were reported in patients on antipsychotics, which indicated the occurrence of disproportionality for this pharmacological class compared with any other drugs. When data were analysed by antipsychotic subclass, disproportionality was found only for atypical but not for typical antipsychotics. When individually analysed by active substances and routes, only a few substances were found to show disproportionality. The disproportionality encountered in this study compared with the mortality associated with other drugs suggests that the active substances under study may be associated with a mortality risk higher than what is assumed currently. Also, it suggests that atypical antipsychotics are likely to have a mortality risk higher than the risk of typical antipsychotics. The disproportionality found for zuclopentixol, in both oral and depot formulations, can be considered to be a drug surveillance signal.
Centre for Research on Drug Safety (CESME), Valladolid University, Valladolid, Spain.
Luis H
LH
Martín Arias
Carlos
C
Treceño Lobato
Susana
S
Pérez García
María
M
Sáinz Gil
Rosario
R
Sanz Fadrique
Pilar
P
García Ortega
D000328:Adult; D016907:Adverse Drug Reaction Reporting Systems / Q000639:trends*; D000368:Aged; D000369:Aged, 80 and over; D014150:Antipsychotic Agents / Q000009:adverse effects*; D016208:Databases, Factual / Q000639:trends; D005260:Female; D006801:Humans; D008297:Male; D001523:Mental Disorders / Q000188:drug therapy* / Q000401:mortality*; D008875:Middle Aged; D009026:Mortality / Q000639:trends; D060735:Pharmacovigilance; D012307:Risk Factors; D013030:Spain / Q000453:epidemiology
D014150:Antipsychotic Agents