Opicapone improves end-of-dose neuropsychiatric fluctuations in patients with Parkinson’s disease

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Introduction Non-motor fluctuations (NMF) represent one of the main complications that patients with Parkinson’s disease (PD) may experience during long-term levodopa treatment. Opicapone (OPC), a COMT-inhibitor indicated for end-of-dose motor fluctuations (MF), has not been extensively investigated for the management of NMF. We evaluate the efficacy of OPC on end-of-dose neuropsychiatric fluctuations, the most frequent and severe NMF. Methods We assessed 15 PD patients who underwent treatment with OPC (PD-OPC) compared to a control group of 15 PD patients (PD-CTRL). All patients had end-of-dose MF and NMF, confirmed by 19-item Wearing-Off Questionnaire (WOQ-19). For each, we identified the first end-of-dose deterioration period through MDS-UPDRS-III administered every 30 min over two consecutive days. On the third day, a comprehensive clinical and neuropsychological battery was administered during this designated period. Subsequently, OPC was prescribed to PD-OPC. After 6 months, patients were re-evaluated using the same baseline assessments during the same end-of-dose period. Results At 6-month follow-up, PD-OPC showed significant improvement in the following tests: WOQ-19 ( p < 0.001), total MDS-UPDRS and each of its four parts ( p < 0.001), NMSS ( p < 0.001), executive functions/attention (Weigl’s, p < 0.001; FAB, p < 0.001; FAS, p < 0.001; STROOP, p = 0.001) and mood related-symptoms (BDI-II, HAM-A; both p = 0.001). There was a slightly significant difference in Visual Search ( p = 0.018), and no differences in RAVLT-I (p = 0.323), and RAVLT-D ( p = 0.155) scores. At follow-up, PD-CTRL showed no significant differences in WOQ-19, motor scales, and neuropsychological tests compared to baseline. Conclusion OPC improved end-of-dose fluctuations in anxiety/depression, and executive functions/attention, while memory and visuospatial abilities showed little or no significant changes.