Comparative effectiveness and safety of antipsychotic drugs in patients with schizophrenia initiating or reinitiating treatment: A Real-World Observational Study.

Abstract

To compare the effectiveness and safety of various second-generation antipsychotics (SGAs), newer oral and long-acting injectable (LAI) SGAs, and first-generation antipsychotics (FGAs) treatments in patients with schizophrenia or schizoaffective disorder (SCZ). This retrospective cohort study included medical administrative information for patients with a diagnosis of SCZ living in Quebec (Canada), initiating or reinitiating at least one antipsychotic (AP) drug (with a clearance baseline period of 12months without any APs). Effectiveness was defined by a reduced risk of hospitalization for mental disorder and discontinuation, and safety by a reduced risk of all-cause death and hospitalization for non-mental disorder, 2years after AP initiation or reinitiation. Cox proportional hazard models were used to estimate the events associated with different antipsychotics compared with oral olanzapine. The study cohort included 19,615 patients initiating or reinitiating an antipsychotic drug between January 2006 and December 2015. Results showed better effectiveness of clozapine (adjusted HR 0.36, 95% CI 0.30-0.42, p<0.0001) and LAI SGAs (adjusted HR 0.56, 95% CI 0.51-0.61, p<0.0001) compared with oral olanzapine when adding discontinuation to hospitalizations for mental disorder as a composite measure of effectiveness, as opposed to oral FGAs (adjusted HR 1.36, 95% CI 1.27-1.46, p<0.0001) and LAI FGAs (adjusted HR 1.22, 95% CI 1.12-1.32, p<0.0001). Most APs were as safe as oral olanzapine. The effectiveness of LAI SGAs and clozapine appears to justify their use and are as safe as a recognized treatment (oral olanzapine) in Quebec (Canada).