Differences in Antipsychotic Treatment Discontinuation Among Veterans With Schizophrenia in the U.S. Department of Veterans Affairs

Objective: Effectiveness of antipsychotic drugs is inferred from relatively small randomized clinical trials conducted with carefully selected and monitored participants. This evidence is not necessarily generalizable to individuals treated in daily clinical practice. The authors compared the clinical effectiveness between all oral and long-acting injectable (LAI) antipsychotic medications used in the treatment of schizophrenia in the U.S. Department of Veterans Affairs (VA) health care system. Methods: This was an observational study utilizing VA pharmacy data from 37,368 outpatient veterans with schizophrenia. Outcome measures were all-cause antipsychotic discontinuation and psychiatric hospitalizations. Oral olanzapine was used as the reference group. Results: In multivariable analysis, clozapine (hazard ratio50.43), aripiprazole long-acting injectable (LAI) (hazard ratio50.71), paliperidone LAI (hazard ratio50.76), antipsychotic polypharmacy (hazard ratio50.77), and risperidone LAI (hazard ratio50.91) were associated with reduced hazard of discontinuation compared with oral olanzapine. Oral first-generation antipsychotics (hazard ratio51.16), oral risperidone (hazard ratio51.15), oral aripiprazole (hazard ratio51.14), oral ziprasidone (hazard ratio51.13), and oral quetiapine (hazard ratio51.11) were significantly associated with an increased risk of discontinuation compared with oral olanzapine. No treatment showed reduced risk of psychiatric hospitalization compared with oral olanzapine; quetiapine was associated with a 36% worse outcome in terms of hospitalizations compared with olanzapine. Conclusions: In a national sample of veterans with schizophrenia, those treated with clozapine, two of the LAI second-generation antipsychotics, and antipsychotic polypharmacy continued the same antipsychotic therapy for a longer period of time compared with the reference drug. This may reflect greater overall acceptability of these medications in clinical practice.