Management of Parkinson's disease psychosis: first-line antipsychotic selection and rationale for continuing, combining, or switching

Introduction: The past decade has seen a paradigm shift in the evaluation and management of Parkinson's disease psychosis (PDP), with the first approval of an antipsychotic in the US in 2016. An evidence-based review by the Movement Disorder Society found pimavanserin and clozapine to be clinically useful, (low-dose) quetiapine to be possibly useful, and all other antipsychotics to be avoided due to motor worsening. Clozapine and quetiapine use can be limited by provoking Parkinson's disease (PD) nonmotor symptoms of somnolence and hypotension. Quetiapine may also be limited by its risk in cognitive impairment. Pimavanserin is not associated with these symptoms. Despite advances in the understanding of PDP and the approval of pimavanserin in the US, clinical questions concerning patient selection, treatment timing, switch strategies, and combination therapy remain. Areas covered: To develop a consensus on first-line and subsequent treatment strategies for PDP, a panel of experts reviewed the clinical presentation and course of PDP, then discussed clinical trial evidence and experience. Expert opinion: PDP is a common but still undertreated sequela of PD progression. Pimavanserin is recommended as a first-line antipsychotic therapy based on its established safety and efficacy. While switching strategies are suggested, further study is needed to assess combination antipsychotic therapy.