Pimavanserin: A Novel Antipsychotic for Parkinson’s Disease Psychosis

Objective: To review the pharmacology, pharmacokinetics, efficacy, safety, and place in therapy of pimavanserin for the treatment of hallucinations and delusions of Parkinson’s disease psychosis (PDP). Data Sources: A comprehensive PubMed search (1966 to January 2017) was conducted using the search terms Parkinson’s disease psychosis, hallucinations, delusions, pimavanserin, and ACP-103. Additional data were obtained from references of identified articles, governmental sources, manufacturer product labeling and website, and Clinicaltrials.gov. Study Selection and Data Extraction: All English-language trials evaluating pimavanserin in PDP were included. Data from review articles were included if relevant to clinical practice. One phase II and 3 phase III trials are discussed. Data Synthesis: Pimavanserin was approved in April 2016 for the treatment of delusions and hallucinations of PDP. One phase II and 2 phase III trials reported no difference for primary outcomes when pimavanserin was compared with placebo. The pivotal phase III ACP-103-020 trial adapted a scale to target more specific symptoms prevalent in PDP and showed that least-squares mean differences of the total PD-adapted Scale for the Assessment of Positive Symptoms score were significantly improved for pimavanserin-treated patients as compared with placebo-treated patients (difference = −3.06; 95% CI [−4.91 to −1.20]; P = 0.0014]). Pimavanserin’s adverse effect profile includes urinary tract infections, falls, peripheral edema, hallucinations, confusion, nausea, and headaches. Conclusion: Pimavanserin is a novel 5-HT_2A inverse agonist that has shown promising results for managing hallucinations and delusions in patients with PDP without worsening motor effects or orthostasis. Yet its high cost and specialty pharmacy access may limit use in clinical practice.