Veterans’ treatment discontinuation differs by type of antipsychotic

Researchers reported differences in antipsychotic treatment discontinuation among veterans with schizophrenia in an observational study published in American Journal of Psychiatry.

Veterans treated with clozapine, two of the long-acting injectable second-generation antipsychotics and antipsychotic polypharmacy maintained the same antipsychotic therapy for a longer duration vs. the reference drug.

“To our knowledge, this is the largest study comparing all-cause discontinuation of antipsychotics and psychiatric hospitalizations in the United States and the first to compare LAI formulations with the same oral medication in a nationwide, multiyear U.S. sample using nonprofit funding,” Mark Weiser, MD, of the Stanley Medical Research Institute in Maryland, and colleagues wrote. “Based on findings from previous studies, we hypothesized that clozapine and LAI antipsychotics would be associated with longer time to discontinuation and fewer psychiatric hospitalizations compared with oral olanzapine and that LAI formulations would be associated with longer time to discontinuation and fewer psychiatric hospitalizations than oral formulations of the same medication.”

The researchers analyzed pharmacy data of 37,368 outpatient veterans with schizophrenia to compare the clinical effectiveness between all oral and LAI antipsychotic medications used for treating schizophrenia in the U.S. Department of Veterans Affairs health care system. All-cause antipsychotic discontinuation and psychiatric hospitalizations served as outcome measures and oral olanzapine as the reference group.

Results of multivariable analysis showed an association between clozapine (HR = 0.43), aripiprazole LAI (HR = 0.71), paliperidone LAI (HR = 0.76), antipsychotic polypharmacy (HR = 0.77) and risperidone LAI (HR = 0.91) and reduced risk for discontinuation compared with oral olanzapine. Further, they noted a significant association between oral first-generation antipsychotics (HR = 1.16), oral risperidone (HR = 1.15), oral aripiprazole (HR = 1.14), oral ziprasidone (HR = 1.13) and oral quetiapine (HR = 1.11) and increased risk for discontinuation compared with oral olanzapine. However, they observed no association between any treatment and reduced risk for psychiatric hospitalization with oral olanzapine. Quetiapine was linked to a 36% worse outcome for hospitalizations compared with olanzapine.

Weiser and colleagues speculated about the reason that those who received antipsychotic polypharmacy experienced longer episodes of continuous therapy and lower rates of treatment discontinuation but not of psychiatric hospitalization compared with those who received oral olanzapine.

“This may be because clozapine, long-acting injectables and polypharmacy are often used as a last resort, and once clinicians have put patients on one of these options, they may be reluctant to change the treatment, because they do not see any other option,” the researchers wrote.