Is the risk of antipsychotic polypharmacy discontinuation dependent on the agents used?

This study assesses the risks and benefits of switching from two to one antipsychotic among participants on two non-clozapine oral antipsychotics, and among those on combinations involving either clozapine or an injectable antipsychotic. Ninety adult participants with schizophrenia or schizoaffective disorder were assigned to stay on polypharmacy or to switch to monotherapy. Half of these participants were receiving combinations of non-clozapine oral antipsychotics and half were receiving combinations involving either clozapine or an injectable antipsychotic. Participants were assessed every 60 days for one year. We examined differences in symptom and side effect trajectories as a function of group assignment and time for both medication groups. Participants who switched from two to one non-clozapine oral antipsychotic experienced significant increases in symptoms relative to stay participants. They also saw significant side effect benefits. Switch participants on combinations involving clozapine or an injectable antipsychotic did not differ over time from stay participants on either symptom or side effect measures. It appears that patients on these combinations can be safely switched to monotherapy. While there may be symptom related risks associated with switching patients on combinations of non-clozapine oral antipsychotics, there are significant health related benefits. Clozapine or injectable antipsychotic monotherapy are recommended options.