Objective: To examine individual responses to pimavanserin in patients with Parkinson’s disease psychosis (PDP) initiating treatment <6 vs ≥6 months and <12 vs ≥12 months after initial psychotic symptoms.

Background: Pimavanserin is the only FDA-approved medication indicated for the treatment of hallucinations and delusions associated with PDP.  Data regarding the relationship between PDP symptom duration and response to treatment are limited, and information from individual response data may have greater relevance to clinical practice than simply reporting mean changes from baseline.

Method: Using data from a pivotal Phase 3, randomized, double-blind, placebo-controlled trial (ACP-103-020), we performed a responder analysis based on the duration of PDP symptoms. Patients with moderate to severe psychotic symptoms and a score ≥3 on a SAPS-HD global item and SAPS-PD non-global item were randomized 1:1 to receive once-daily pimavanserin (34 mg) or placebo for 6 weeks. The primary outcome was the mean change from baseline to week 6 on the SAPS-PD. Individual responses were categorized by SAPS-PD score point reductions of ≥1, ≥3, ≥5, ≥7, ≥10, or complete response (SAPS-PD=0), as well as increases >1 (worsening) or no change.

Results: A total of 95 patients treated with pimavanserin were included in this analysis. Patients with PDP symptoms <6 months had numerically greater rates of response to pimavanserin at all levels compared to those with symptoms ≥6 months [Table 1]. Notably, 30.8% of those who initiated pimavanserin <6 months after initial psychotic symptoms achieved a complete response (CR, no hallucinations or delusions), vs 11.0% who initiated treatment ≥6 months after PDP symptom onset. A trend for greater response rates was also seen in patients treated <12 vs ≥12 months after PDP symptoms began (CR, 22.6% vs 9.4%, respectively) [Table 2]. Differences were not statistically significant.

Conclusion: Our analysis found that, at all levels of response, a greater percentage of patients with PDP responded to pimavanserin when treated <6 months after initial psychotic symptoms compared with patients treated ≥6 months after initial psychotic symptoms (CR, 30.8% vs 11.0%); findings were consistent for durations of <12 vs ≥12 months since initial symptoms.

Table 1

Table 2

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MDS Abstracts - https://www.mdsabstracts.org/abstract/duration-of-illness-and-response-to-pimavanserin-in-parkinsons-disease-psychosis-post-hoc-analysis-of-clinical-trial-data/