Caroline Kruse, Daniel Weintraub, John Duda, James F Morley
Psychosis in Parkinson's disease (PD) is a common and debilitating non-motor symptom that can occur at any stage of the disease. PD psychosis (PDP) manifests as a diverse clinical spectrum that can include misperceptions, passage and presence phenomena, hallucinations, and delusions, alone or in combination. This review explores the epidemiology and underlying neurobiological mechanisms of psychosis in PD, describes the symptom spectrum experienced by patients, and reviews the evidence supporting current and future therapies for psychosis in PD. Pimavanserin and clozapine are the only pharmacologic therapies for PDP that have been found to be efficacious in randomized controlled trials, though quetiapine is most frequently used despite lacking positive trial results. Future research that continues to clarify the exact pathophysiology of psychosis in PD will improve the current therapeutic approaches, and ongoing randomized clinical trials of these therapies are necessary to identify the safest and most efficacious treatments for PD patients with psychosis.