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

Acta Psychiatr Scand. 2022 May;145(5):456-468. doi: 10.1111/acps.13413. Epub 2022 Mar 1.


Objective: 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).

Methods: 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 12 months 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, 2 years after AP initiation or reinitiation. Cox proportional hazard models were used to estimate the events associated with different antipsychotics compared with oral olanzapine.

Results: 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.

Conclusion: 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).

Keywords: antipsychotic; effectiveness; observational studies; safety; schizophrenia.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antipsychotic Agents* / adverse effects
  • Clozapine* / adverse effects
  • Delayed-Action Preparations / therapeutic use
  • Humans
  • Olanzapine / therapeutic use
  • Retrospective Studies
  • Schizophrenia* / diagnosis


  • Antipsychotic Agents
  • Delayed-Action Preparations
  • Clozapine
  • Olanzapine