To evaluate the efficacy and safety of pimavanserin in Parkinson’s disease psychosis (PDP) through a meta-analysis of placebo-controlled randomized controlled trials (RCTs).

RCTs comparing pimavanserin with placebo in PDP were identified through systematic searches of PubMed and ClinicalTrials.gov. The primary outcome was psychosis severity measured by SAPS-PD or SAPS-H+D. Secondary outcomes included UPDRS II/III (motor function) and adverse events such as falls, orthostatic hypotension, hallucinations, headache, and confusional state. Random-effects models were used to calculate standardized mean differences (SMD), mean differences (MD), or risk ratios (RR) with 95% confidence intervals (CI).

Four trials (PMID 19907417, NCT01174004, NCT00477672, NCT00658567) were included. Pimavanserin significantly reduced psychosis severity (SAPS: SMD −0.86; 95% CI −1.53 to −0.20; p = 0.011). Motor function showed no significant change (UPDRS II/III: MD −0.08; 95% CI −1.55 to 1.39; p = 0.92). Most adverse events were not significantly different from placebo, including falls (RR 0.69; 95% CI 0.42–1.12), hallucinations (RR 0.96; 95% CI 0.24–3.81), headache (RR 0.58; 95% CI 0.28–1.21), and confusional state (RR 1.42; 95% CI 0.67–3.02). Orthostatic hypotension showed a lower risk with pimavanserin (RR 0.36; 95% CI 0.17–0.76). Heterogeneity was high for efficacy outcomes (I² > 90%) but low for safety outcomes.

Pimavanserin significantly improves psychosis in PDP without worsening motor symptoms. Most adverse events, including confusion, were not significantly different from placebo, except for a possible reduction in orthostatic hypotension. High heterogeneity and wide prediction intervals warrant cautious interpretation and further head-to-head trials.