Antipsychotics and mortality in a nationwide cohort of 29,823 patients with schizophrenia

INTRODUCTION:It has remained controversial if antipsychotic treatment is associated with increased or decreased mortality among patients with schizophrenia, and if there are any clinically meaningful differences between specific agents and routes of administration. METHODS:We linked prospectively gathered nationwide register-based data during 2006-2013 to study all-cause mortality among all patients aged 16-64years with schizophrenia in Sweden (N=29,823 in total; N=4603 in the incident cohort). Multivariate Cox regression models were adjusted for clinical and sociodemographic covariates. Sensitivity analyses with the incident cohort were conducted to control for survival bias. RESULTS:During the mean follow-up of 5.7years, 2515 patients (8.4%) died. During the maximum follow-up (7.5years), the lowest cumulative mortality was observed for second generation (SG) long-acting injection (LAI) use (7.5%). Adjusted hazard ratios (aHRs) compared to SG LAI use were 1.37 (95%CI 1.01-1.86) for first generation (FG) LAIs, 1.52 (1.13-2.05) for SG orals, 1.83 (1.33-2.50) for FG orals, and 3.39 (2.53-4.56) for nonuse of antipsychotics. Concerning specific agents, the lowest mortality was observed for once-monthly paliperidone LAI (0.11, 0.03-0.43), oral aripiprazole (0.22, 0.15-0.34), and risperidone LAI (0.31, 0.23-0.43). In pairwise comparison, LAIs were associated with 33% lower mortality than equivalent orals (0.67, 0.56-0.80). The results with incident cohort were consistent with the primary analyses. CONCLUSIONS:Among patients with schizophrenia, LAI use is associated with an approximately 30% lower risk of death compared with oral agents. SG LAIs and oral aripiprazole are associated with the lowest mortality.