Objective: This study aims to identify clinical predictors of continuous subcutaneous infusion (CSCI)-induced psychosis to understand its potential mechanisms and evaluate predictive measures for its early detection and management.

Background: Atypical psychosis, characterized by severe delusions, paranoia, and auditory or somatic hallucinations, is a notable complication of the 24-hour CSCI foslevodopa/foscarbidopa therapy in Parkinson disease (PD).

Method: The present retrospective cohort study included PD patients treated with CSCI (n = 23) and a database of an independent sample of the PD database (n = 94) at Osaka University Hospital. In the CSCI cohort, clinical data such as psychosis information and data from PD-related questionnaires such as 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 occurring within a year of CSCI initiation.

Results: Six patients developed atypical psychosis, with all the psychosis cases occurring within six months and four discontinuing CSCI due to psychosis. Patients who developed atypical psychosis had significantly higher QUIP-CS scores than those who did not (adjusted p = 0.00021). Linear regression identified QUIP-CS as the sole predictor of atypical psychosis onset (coefficient = 0.199, p < 0.001). Among the 39 PDQ39 sub-items, item 27 showed a significant correlation with QUIP-CS (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 (r = 0.770, p = 0.0000704). Lastly, PDQ39_sub5 effectively stratified survival curves for psychosis onset (p = 0.008).

Conclusion: 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, the PDQ39_sub5 offers a practical way to identify individual psychosis risk. These findings potentially offer tailored strategies to predict and manage atypical psychosis in PD patients receiving advanced dopaminergic therapies.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/atypical-psychosis-in-parkinson-disease-a-retrospective-study-on-24-hour-continuous-subcutaneous-infusion-foslevodopa-foscarbidopa-therapy/