Opicapone in Parkinson's Disease on Levodopa-Carbidopa Intestinal Gel Treatment: A Pilot, Randomized Study

Background Levodopa-carbidopa intestinal gel infusion (LCIG) is an effective therapy for advanced Parkinson's disease (PD). Opicapone (OPC) is an enzyme inhibitor that enhances the bioavailability of levodopa in the brain. Objectives This study evaluates the effect of Opicapone addition in PD-LCIG patients, assessing its impact on motor fluctuations and dyskinesias. Secondly, the study analyses the impact of OPC on non-motor symptoms, LCIG dosage, and peripheral neuropathy. Method In this pilot study, 22 PD patients on LCIG were randomized to receive OPC or not, based on persistent or reemergent fluctuations. The Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS), Unified Dyskinesia Rating Scale (UDysRS), Montreal Cognitive Assessment (MoCA), electroneurography (ENG), LCIG doses, homocysteine, vitamin B12, and folic acid levels were measured at baseline (T0) and after 12 months (T1). Results Eleven patients added OPC (addOPC group), while 11 maintained standard treatment (nOPC group). At baseline, both groups had similar disease duration and severity. At T1, the addOPC group showed significant: (i) improvement in motor fluctuations evaluated by the MDS-UPDRS part IV; (ii) reduction in dyskinesias (UDyRS); (iii) decrease in LCIG infusion rate; (iv) improvement in motor and non-motor symptoms (MDS-UPDRS parts I-III); (v) increase in Vitamin B12. No significant differences were observed in the ENG data, and no serious adverse events occurred. Four addOPC patients (36%) discontinued OPC after 15 +/- 2 months, mainly due to hallucinations. Conclusions OPC addition appeared well tolerated and beneficial in reducing motor fluctuations, dyskinesia, and LCIG dose. Randomized controlled trials are needed to confirm these findings.