Psychosis is a common feature of Parkinson’s Disease (PD), affecting approximately 50% of PD patients during their disease course. The INSYTE study was the first prospective, real-world, observational study examining the outcomes of both treated and untreated patients with PD Psychosis (PDP).

PDP patients were enrolled from 76 US academic centers and community sites from 03/21/2017 to 03/08/2021. Patients were included in the final analytical cohort if they had a baseline visit and at least 1 follow-up visit within 3 years; due to the variability of follow-up for each patient within the 3-year period, all study outcomes were assessed in patients with at least one baseline and two follow-up visits within 1 year. No specific visit schedule was imposed; all interactions were established by the investigators. Questionnaires were completed at follow-up visits and assessments focused on PDP treatment utilization, treatment patterns, clinical outcomes, caregiver burden, quality of life, and resource utilization.

760 patients were initially enrolled; 635 patients (84%) were included in the final study group, and 441 patients (69%) were included in the analysis. 281 patients (64%) had no antipsychotic treatment at enrollment (untreated group) vs 160 (36%) who had received an antipsychotic at enrollment (treated group). At enrollment, patients in the untreated vs treated group, respectively, had a mean PD duration of 8.05 vs 10.23 years, mean duration of PDP features of 2.20 vs 3.10 yrs, and had a PDP diagnosis for a mean of 1.42 vs 2.16 yrs. Most patients in the untreated group (n=221, 77%) received no antipsychotics through follow-up. The groups were balanced in terms of age (mean 73.9 vs 73.4 yrs) and sex (65.1% vs 63.1% male). The untreated group had higher rates of hypertension (44.5% vs 36.8%) and diabetes (12.8% vs 8.8%); however, the treated group had higher rates of depression (25.6% vs 41.3%) and anxiety (22.8% vs 26.9%). The percent change from baseline at 12 months in total psychosis, hallucination, and delusion scores for the untreated group showed greater worsening than the treated group: 32.3% vs 29.3%; 29.3 % vs 25.0%; and 29.3 % vs 25.0%, respectively, as did daytime sleepiness scores (51.6% vs 40.8%). Measures of PD severity (non-motor and motor MDS-UPDRS scores) and health-related quality of life showed less worsening for the untreated group vs treated group at 12 months. Caregiver burden (per the ZBI) was lower in the untreated group vs the treated group (81.5% vs 90.0%).

In this descriptive analysis, untreated patients had shorter duration of PD, fewer PDP symptoms at baseline, and lower rates of mental health comorbidities vs treated patients. The untreated PDP patients had greater worsening in their psychosis and sleepiness scores at 12 months versus the treated group, yet remained untreated. Future studies are needed to better understand clinicians’ rationale for withholding PDP treatment.

Acadia Pharmaceuticals, Inc