Duration of Illness and Complete Response to Pimavanserin in Parkinson’s Disease Psychosis: Analysis of Pooled Clinical Trial Data

Pimavanserin is the only FDA-approved medication indicated for treatment of hallucinations and delusions associated with Parkinson’s disease psychosis (PDP). Earlier treatment of mild PDP symptoms may lower the risk of later deterioration; however, evidence for potential benefit of early treatment is limited. In a pivotal trial, ~14% of patients achieved complete response (CR) with pimavanserin. We explored the potential association between time since PDP diagnosis and pimavanserin initiation in patients with CR. Data were pooled from PDP patients treated with once-daily pimavanserin (34mg) in two 6-week placebo-controlled trials. The probability of achieving CR, defined as a reduction of SAPS-PD score to 0 at week 6, and its association with timing of treatment initiation (PDP duration) was assessed using logistic regression. Of the 135 patients evaluated, 21 achieved CR. Patients who initiated pimavanserin with PDP durations < 6 or < 12 months had a greater probability of achieving CR vs those who initiated ≥6 months (odds ratio [OR]: 3.11, 95% CI: 1.03–9.42, p=0.045) or ≥12 months (OR: 2.59, 95% CI: 1.01–6.66, p=0.049). Cutoffs of < 18 months or < 24 months did not indicate clear advantage over ≥18 months (OR: 1.81, 95% CI: 0.70–4.69, p=0.225) or ≥24 months (OR: 2.17, 95% CI: 0.79–6.00, p=0.135). After adjusting for baseline SAPS-PD, the trend still favored PDP duration < 12 vs ≥12 months (OR: 2.27, 95% CI: 0.85–6.08, p=0.102). Our analysis found that early pimavanserin treatment is associated with higher probability of complete resolution of PDP symptoms.