Risk of death associated with the use of conventional vs. atypical antipsychotic medications: evaluating the use of the Emilia-Romagna Region database for pharmacoepidemiological studies

Abstract

SUMMARYWhat is known and objective: Since 2005, a mounting base of evidence has identified that conventional antipsychotic medications are associated with an increased risk of mortality among elderly patients when compared to atypical antipsychotics. This study sought to explore the feasibility of using the EmiliaRomagna Region (RER) database for comparative safety analyses by replicating and refining risk estimates of this well-known drug safety example through meta-analysis. Methods: We identified a cohort of 23 681 Italian RER patients (aged ≥65) who initiated treatment with a conventional or atypical antipsychotic between 1 July 2009 and 30 June 2011. We compared 180-day mortality using Cox proportional hazards models adjusted for risk factors for death, use of other medications and measures of health services utilization intensity, all measured before antipsychotic initiation. We conducted a metaanalysis of studies with similar methods against which to compare our results. Results: Among 14 462 and 9219 patients prescribed conventional and atypical antipsychotics, respectively, we observed 2402 (16Á6%) and 821 (8Á9%) deaths during follow-up. Conventional antipsychotic initiators were older and generally had higher prevalence of outcome risk factors and higher baseline health service use intensity. The crude hazard ratio (HR) was 1Á95 [95% confidence interval (CI), 1Á80-2Á11], which decreased to 1Á47 (95% CI, 1Á35-1Á60) after full adjustment. We identified seven published studies that examined this association using similar methods. The pooled HR from these studies was 1Á34 (95% CI, 1Á28-1Á39). Including our study, the meta-analysis yielded a summary estimate of 1Á35 (95% CI, 1Á31-1Á40) and did not introduce any heterogeneity (I 2 = 0%; P = 0Á455). What is new and conclusions: Our results support the use of the RER database for pharmacoepidemiological studies and provide an up-to-date and pooled estimate of the magnitude of the association between mortality and conventional vs. atypical antipsychotics. WHAT IS KNOWN AND OBJECTIVEIn April 2005, the US Food and Drug Administration issued a public health advisory highlighting an association between atypical antipsychotic medications and increased mortality in elderly patients.1 In the wake of this advisory, subsequent studies found an even greater risk of mortality associated with the use of conventional antipsychotics as compared to atypical antipsychotics (Wang et al.,2 Schneeweiss et al. 3), and since then, the FDA, EMA and other regulatory and health agencies have expanded this alert to include conventional antipsychotics.1,4,5 Most of the studies on which these regulatory actions were based were conducted in large, population-based electronic healthcare databases comprising administrative claims from multiple sources, including pharmacies, hospitals, and outpatient physicians.Electronic healthcare databases from many countries have been used for a number of research purposes including to evaluate physician prescribing, drug utilization, drug adverse effects...

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