Real-world neuropsychiatric safety profile of foslevodopa/foscarbidopa infusion in advanced Parkinson's disease
TL;DR
Frontal executive dysfunction emerged as a significant risk factor, suggesting specific frontal screening should be routine in candidacy evaluation for cognitively frail patients and Preventive strategies to reduce risk are proposed and discussed.
Abstract
To describe demographic, clinical, and neuropsychiatric safety outcomes in a cohort of PD patients treated with LDp/CDp infusion in a real-world setting. We retrospectively analyzed a database of 77 consecutive PD patients treated with LDp/CDp at two Italian tertiary referral centers, with a minimum 6-month follow-up. Baseline cognitive, epidemiological, and clinical variables were assessed to determine potential neuropsychiatric adverse event (NAE) risk factors. Patients had long disease duration (13.8±6.4 years) and moderate-to-severe motor burden (MDS–UPDRS III: 34.4±15). Pre-existing cognitive impairment (MCI 41.6%, dementia 7.8%), prior hallucinations (26%), and impulse control disorders (27.3%) were frequent. At 6 months, mean L-dopa equivalent daily dose increased by ~300 mg (p<0.001). The dropout rate was 16.9% (13 patients), mainly due to AEs (38.5%), bridging to DBS (23%), or device intolerance (15.4%). New-onset NAEs emerged in 17 patients (22.1%) at a median of 30 days, predominantly hallucinations (41.2%) and psychosis (29.4%). Most events were efficiently managed via careful infusion rate adjustments and low-dose antipsychotics, achieving resolution or improvement in 82% of cases. Three patients (18%) discontinued therapy due to severe NAEs. Multivariable regression analysis confirmed baseline Frontal Assessment Battery (FAB) score as the primary independent predictor of NAE development (OR 0.707, p=0.010). LDp/CDp infusion is well-tolerated. Although NAEs were more frequent than in pivotal trials, they were largely manageable. Frontal executive dysfunction emerged as a significant risk factor, suggesting specific frontal screening should be routine in candidacy evaluation for cognitively frail patients. Preventive strategies to reduce risk are proposed and discussed.