Safety of antipsychotic drugs: A systematic review of disproportionality analysis studies

Antipsychotic drugs are commonly prescribed, mainly for the treatment of schizophrenia and other psychotic disorders. Disproportionality analysis of pharmacovigilance data from national and international databases have been recently utilized to investigate the side-effect profiles of antipsychotics and have provided unique insights of their safety. Among several national and international spontaneous reporting databases the databases of the World Health Organization (VigiBase), of the European Medicines Agency (EudraVigilance) and the US Food and Drug Administration (FAERS) incorporate millions of Individual Case Safety Reports. The aim of our study was to systematically review published disproportionality analyses on antipsychotic drugs, in order to summarize the current state of methodology and potential strengths of this analysis while highlighting safety signal generated for these pharmacological group. PubMed was searched using a search algorithm combining terms for antipsychotic drugs and disproportionality analysis. A total of 39 articles were found to be eligible corresponding to 38 original disproportionality studies. Different measures of disproportionality were used in each study: reporting odds ratio (ROR), proportional reporting ratio (PRR), empirical Bayes geometric mean (EBGM) and the information component (IC). Despite the inherent limitations of the pharmacovigilance databases disproportionality analysis provides complemented evidence from RCTs on the safety of antipsychotics, especially regarding participants often excluded from RCTs, such as pregnant and breastfeeding women, children and participants with drug abuse, comorbidities or concomitant medications.