Objective: 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. Method of Research: 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. Results: 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 (p=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 (p=0.0014, effect size=0.50). Secondary outcomes were also significantly 
improved: Clinical Global Impression of Severity (CGI-S) (p=0.0007, effect 
size=0.52) and Clinical Global Impression of Improvement (CGI-I) (p=0.0011, 
effect size=0.51), caregiver burden (p=0.0016, effect size=0.50), nighttime 
sleep (p=0.0446, effect size=0.31), and daytime wakefulness (p=0.012, effect 
size=0.39). Conclusion: 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.