Antipsychotic Polypharmacy for Treatment Resistant Schizoaffective Disorder: A Case Report

This case presents a male in his early 20s with schizoaffective disorder and cannabis use disorder presenting with treatment resistance demonstrated by inadequate control of psychotic symptoms despite multiple trials of antipsychotics. The patient was experiencing positive symptoms, including hyper-religiosity, hallucinations, mood lability, agitation, and aggression. The patient and next of kin were unable to provide consent for clozapine due to concerns for monitoring requirements. The patient continued paliperidone long-acting injectable (LAI) 234 milligrams (mg) every four weeks and divalproex 750 mg twice per day (BID) and was started on haloperidol with titration to 2 mg BID. Following the addition of a second antipsychotic agent, the patient exhibited marked improvement with reduced intensity of perceptual disturbances. This case underscores the potential benefits and challenges of antipsychotic polypharmacy in addressing residual psychosis and improving functional outcomes. We also provide an overview of available evidence for and against antipsychotic polypharmacy, defined as two or more antipsychotic medications used in a patient concurrently, as well as alternative non-antipsychotic agents for treatment-resistant schizophrenia.