Ge Lindun, Kimura Yasuyoshi, Kakuda Keita, Ogawa Kotaro, Kajiyama Yuta, Asai Kanako, Taniguchi Seira, Beck Goichi, Nishio Yoshiyuki, Kim Jee Hyun, Ikenaka Kensuke, Mochizuki Hideki
Department of Neurology, Osaka University Graduate School of Medicine, Suita, Japan.
Department of Neurology, Kawasaki Medical School, Kurashiki, Japan.
Neurol Clin Pract. 2025 Oct;15(5):e200534. doi: 10.1212/CPJ.0000000000200534. Epub 2025 Sep 8.
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.
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 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.
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 = 0.0032). Linear regression identified QUIP-CS as the sole predictor of atypical psychosis onset (coefficient = 0.199, < 0.001). Among the PDQ39 subitems, item 27 showed a significant correlation with QUIP-CS scores ( = 0.722, adjusted = 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 ( = 0.770, = 0.0000704). This association was independently confirmed in the PD database cohort ( = 0.415, = 0.00003). Finally, PDQ39_sub5 effectively stratified survival curves for psychosis onset in the CSCI cohort ( = 0.008).
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.
非典型精神病以严重的妄想、偏执以及听觉或躯体幻觉为特征，是帕金森病（PD）患者持续皮下输注（CSCI）福司来沃多巴/福司卡比多巴治疗的一种显著并发症。本研究的目的是确定CSCI所致精神病的临床预测因素，以了解其潜在机制，并评估早期检测和管理的预测措施。
这项回顾性队列研究纳入了接受CSCI治疗的PD患者（n = 23）以及来自大阪大学医院的一个独立的PD数据库队列（n = 94）。在CSCI队列中，收集了诸如精神病信息以及帕金森病问卷（PDQ39）和帕金森病冲动控制障碍问卷 - 当前症状（QUIP - CS）的答案等临床数据。统计分析包括独立检验和线性回归，以确定CSCI开始后一年内非典型精神病的预测因素。在PD数据库队列中，使用相关性分析探索QUIP - CS评分与其他临床参数之间的潜在关系。
在23例患者中，6例出现非典型精神病，均在6个月内发生，其中4例停止了CSCI治疗。出现非典型精神病的患者在CSCI治疗前的QUIP - CS评分显著更高（校正P = 0.0032）。线性回归确定QUIP - CS是非典型精神病发作的唯一预测因素（系数 = 0.199，P < 0.001）。在PDQ39子项目中，第27项与QUIP - CS评分显示出显著相关性（r = 0.722，校正P = 0.0128）。此外，由PDQ39的第20、27、29、31和36项组成的综合评分（PDQ39_sub5）与QUIP - CS评分的相关性更强（r = 0.770，P = 0.0000704）。这种关联在PD数据库队列中得到了独立证实（r = 0.415，P = 0.00003）。最后，PDQ39_sub5有效地对CSCI队列中精神病发作的生存曲线进行了分层（P = 0.008）。
CSCI所致精神病与典型PD精神病中观察到的视幻觉不同，可能涉及中脑边缘回路机制以及与多巴胺调节异常相关的冲动控制行为。虽然QUIP - CS在临床实践中很少使用，但广泛使用的PDQ39_sub5提供了一种识别个体精神病风险的实用方法。这些发现可能为接受晚期多巴胺能治疗的PD患者预测和管理非典型精神病提供量身定制的策略。
