Neuropsychiatric Adverse Events Associated With Foslevodopa/Foscarbidopa Continuous Subcutaneous Infusion in Clinical Practice: A Multicenter Study

BACKGROUND: Foslevodopa/foscarbidopa continuous subcutaneous infusion (LDp/CDp CSI) has emerged as an effective and well-tolerated therapy for reducing OFF and increasing non-troublesome ON in advanced Parkinson's disease (PD). Neuropsychiatric adverse events (AEs) have been reported in both clinical trials and real-world studies, with some real-world cohorts suggesting higher rates among patients with prior hallucinations or cognitive impairment. The present study aimed to determine the incidence and risk factors of neuropsychiatric AEs in a large prospective real-world cohort. METHODS: We analyzed data from the DATs-PD GETM Spanish Registry, an observational, prospective, multicenter, open-label study. RESULTS: 214 patients treated with LDp/CDp CSI were included. Median age was 69 years, and median disease duration was 12 years. At baseline, 35% had cognitive impairment, 25.7% hallucinations/psychosis, and 26.2% impulse control disorders (ICDs). During follow-up after initiation (median 163 days), 19.2% developed at least one neuropsychiatric AE, mostly mild-moderate, and only 2.3% required device removal. Most events occurred more than 1 month after treatment initiation. In adjusted Cox, none of the evaluated variables were associated with the development of hallucinations/psychosis/confusion. The presence of ICD at baseline was associated with an increased risk of ICD-related AEs. CONCLUSION: Neuropsychiatric AEs, mainly hallucinations/psychosis, occurred in a clinically relevant proportion of patients treated with LDp/CDp CSI. However, they were generally mild-to-moderate and rarely led to treatment discontinuation. Except for ICD, baseline cognitive and psychotic features were not associated with higher incidence. These findings support its use in appropriately selected patients while highlighting the importance of individualized careful clinical monitoring.