Objective:

To evaluate the impact of baseline sleep disturbances on antipsychotic response to pimavanserin vs placebo in patients with Parkinson’s disease psychosis (PDP).

Background:

Sleep-related disturbances are commonly associated with PDP. Pimavanserin is approved in the US for hallucinations and delusions associated with PDP, but the impact of sleep disturbances on pimavanserin response is unclear.

Design/Methods:

To identify patients with sleep-related disturbances, data from the pivotal phase 3 trial (NCT01174004) were stratified by baseline Scales for Outcomes in Parkinson’s Disease-nighttime sleep (SCOPA-NS) scores (≥7 or <7) and SCOPA-daytime sleepiness (SCOPA-DS) scores (≥5 or <5). The impact of baseline sleep disturbances was assessed using a mixed model for repeated measures including treatment, visit, SCOPA subgroup, and their interactions. The primary endpoint was the least squares mean (LSM) change from baseline in Scale for the Assessment of Positive Symptoms-Parkinson's Disease (SAPS-PD) score at week 6. Treatment differences (LSMD) vs placebo were estimated within each SCOPA subgroup, and an interaction test was conducted (not powered to detect differences; all nominal P values).

Results:

Overall, pimavanserin improved psychosis symptoms vs placebo at week 6: SAPS-PD LSMD (95% CI), −3.02 (−4.89, −1.14); P=0.0018. For baseline SCOPA-DS<5, SAPS-PD LSMD (95% CI) was −5.27 (−8.41, −2.12); P=0.0015; for SCOPA-DS≥5, −1.97 (−4.24, 0.29); P=0.0872 (interaction test P=0.1429). For baseline SCOPA-NS<7, SAPS-PD LSMD (95% CI) was −3.35 (−5.79, −0.92); P=0.0074; for baseline SCOPA-NS≥7, −2.56 (−5.53, 0.40); P=0.0893 (interaction test P=0.6716). Notably, patients with nighttime sleep disturbances (baseline SCOPA-NS≥7) experienced sleep improvement with pimavanserin vs placebo: SCOPA-NS LSMD (95% CI), −2.54 (−4.14, −0.93); P=0.0025.

Conclusions:

Pimavanserin demonstrated consistent antipsychotic efficacy vs placebo in patients with PDP regardless of baseline sleep-disturbance status. Additionally, patients with baseline impairment in nighttime sleep experienced improved nighttime sleep with pimavanserin. These findings support the consistent efficacy of pimavanserin in the presence or absence of daytime or nighttime sleep disturbance.