Atypical Psychosis in Parkinson Disease: A Retrospective Study on 24-Hour Continuous Subcutaneous Infusion of Foslevodopa/Foscarbidopa.

Abstract

Background and objectives: Atypical psychosis, characterized by severe delusions, paranoia, and auditory or somatic hallucinations, is a notable complication of continuous subcutaneous infusion (CSCI) of foslevodopa/foscarbidopa therapy in Parkinson disease (PD). The aim of this study was to identify clinical predictors of CSCI-induced psychosis to understand its potential mechanisms and evaluate predictive measures for early detection and management.

Methods: This retrospective cohort study included patients with PD treated with CSCI (n = 23) and an independent PD database cohort (n = 94) from Osaka University Hospital. In the CSCI cohort, clinical data such as psychosis information and answers from Parkinson's Disease Questionnaire (PDQ39) and the Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease-Current Symptoms (QUIP-CS) were collected. Statistical analyses included independent t tests and linear regression to identify predictors of atypical psychosis within a year of CSCI initiation. In the PD database cohort, potential relationships between QUIP-CS scores and other clinical parameters were explored using correlational analyses.

Results: Among the 23 patients, 6 developed atypical psychosis, all occurring within 6 months, with 4 of them discontinuing CSCI. Patients who developed atypical psychosis had significantly higher QUIP-CS scores before CSCI (adjusted p = 0.0032). Linear regression identified QUIP-CS as the sole predictor of atypical psychosis onset (coefficient = 0.199, p < 0.001). Among the PDQ39 subitems, item 27 showed a significant correlation with QUIP-CS scores (r = 0.722, adjusted p = 0.0128). Furthermore, a composite score comprising PDQ39 items 20, 27, 29, 31, and 36 (PDQ39_sub5) showed an even stronger correlation with QUIP-CS scores (r = 0.770, p = 0.0000704). This association was independently confirmed in the PD database cohort (r = 0.415, p = 0.00003). Finally, PDQ39_sub5 effectively stratified survival curves for psychosis onset in the CSCI cohort (p = 0.008).

Discussion: CSCI-induced psychosis is distinct from visual hallucinations observed in typical PD psychosis and likely involves mechanisms in mesolimbic circuits and impulsive-compulsive behaviors associated with dopamine dysregulation. While QUIP-CS is rarely used in clinical practice, widely used PDQ39_sub5 offers a practical way to identify individual psychosis risk. These findings potentially offer tailored strategies to predict and manage atypical psychosis in patients with PD receiving advanced dopaminergic therapies.