Pimavanserin: A Novel Drug Approved to Treat Parkinson's Disease Psychosis.

Abstract

<i>Objective</i>: Pimavanserin is the first United States Food and Drug Administration (FDA)-approved treatment for Parkinson's disease psychosis (PDP). This article reviews the safety, efficacy, and pharmacology data for pimavanserin and its role in therapy. <i>Method of Research:</i> Initial literature sources were identified via MEDLINE search (1946-September 2016) of pimavanserin and ACP-103 (original molecular designation). Reference review and search of FDA.gov and clinicaltrials.gov yielded additional studies. English-language studies of pimavanserin for PDP were evaluated. Animal studies were excluded. Randomized, controlled trials (RCTs) were prioritized. <i>Results:</i> Four RCTs were identified. In each, pimavanserin was well-tolerated with few adverse effects and no worsening of motor symptoms. A Phase II trial displayed a nonsignificant trend toward Scale for Assessment of Positive Symptoms (SAPS) improvement (<i>p</i>=0.09), with significant benefits in secondary efficacy markers. However, two Phase III trials, including one that was terminated early, failed to show significant SAPS improvement. A third Phase III trial with an improved research design utilized a nine-item subset of the SAPS, the SAPS-PD, as the primary outcome and demonstrated that pimavanserin 40mg was effective in improving PDP compared to placebo (<i>p</i>=0.0014, effect size=0.50). Secondary outcomes were also significantly improved: Clinical Global Impression of Severity (CGI-S) (<i>p</i>=0.0007, effect size=0.52) and Clinical Global Impression of Improvement (CGI-I) (<i>p</i>=0.0011, effect size=0.51), caregiver burden (<i>p</i>=0.0016, effect size=0.50), nighttime sleep (<i>p</i>=0.0446, effect size=0.31), and daytime wakefulness (<i>p</i>=0.012, effect size=0.39). <i>Conclusion</i>: Evidence suggests pimavanserin attenuates PDP symptoms with few adverse effects and little risk of worsening motor function. With limited treatment options for PDP, pimavanserin represents an important therapeutic innovation.