Emerging role of psychosis in Parkinson's disease: From clinical relevance to molecular mechanisms

Abstract

Parkinson’s disease (PD) is the second most common neurodegenerative disease. Psychosis is one of the common psychiatric presentations in the natural course of PD. PD psychosis is an important non-motor symptom, which is strongly correlated with a poor prognosis. Increasing attention is being given to PD psychosis. In this opinion review, we summarized and analyzed the identification, screening, epidemiology, mechanisms, risk factors, and therapeutic approaches of PD psychosis based on the current clinical evidence. PD psychosis tends to have a negative effect on patients' quality of life and increases the burden of family caregiving. Screening and identification in the early stage of disease is crucial for establishing tailored therapeutic strategies and predicting the long-term outcome. Development of PD psychosis is believed to involve a combination of exogenous and endogenous mechanisms including imbalance of neurotransmitters, structural and network changes, genetic profiles, cognitive impairment, and antiparkinsonian medications. The therapeutic strategy for PD psychosis includes reducing or ceasing the use of dopaminergic drug, antipsychotics, cholinesterase inhibitors, and non-pharmacological interventions. Ongoing clinical trials are expected to provide new insights for tailoring therapy for PD psychosis. Future research based on novel biomarkers and genetic factors may help inform individualized therapeutic strategies.

Rethinking Clozapine: Lights and Shadows of a Revolutionary Drug

“…In 2002, the European Agency for the Evaluation of Medicinal Products (EMEA) approved Clozapine for the treatment of psychotic symptoms in patients with Parkinson's Disease (PD) after failure of standard treatments [30]. Indeed, about 25-30% of Parkinson's patients experience psychotic symptoms, with a constant increase linked to the duration of illness and a great impact on quality of life [87]. The indication was mainly supported by data from the Parkinson Study Group of 1999 and by the FDA's Orphan Drug Division, which demonstrated a reduction in symptoms, by 9.3 points vs. 2.6 points with placebo, with Clozapine at a mean dose of approximately 25 mg/day, as confirmed by subsequent studies [29,[88][89][90][91].…”