Objective: We aim to evaluate the efficacy of Opicapone (OPC) on end-of-dose neuropsychiatric fluctuations, the most frequent and severe non-motor fluctuations (NMF) in Parkinson’s disease (PD) patients [1].

Background: NMF represent one of the main complications that patients with PD may experience during long-term levodopa treatment [1].  OPC, a COMT inhibitor indicated for end-of-dose motor fluctuations (MF), has not yet been extensively investigated for the management of NMF [2,3].

Method: We assessed 15 PD patients who will take OPC (PD-OPC) compared to a control group of 15 PD patients (PD-CTRL) (Table 1). All patients had end-of-dose MF and NMF, confirmed by 19-item Wearing-Off Questionnaire (WOQ-19). For each patient, we identify the first end-of-dose deterioration period through MDS-UPDRS-III administered every 30 minutes 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) (Table 2), total MDS-UPDRS and each of its four parts (p<0.001), NMSS (p<0.001) (Table 3), executive functions/attention (Weigl’s, p<0.001; FAS fluency, p<0.001; STROOP, p=0.003) and mood related symptoms (BDI-II, HAM-A; both p<0.001) (Table 4). There were no significant differences in Visual Search (p=0.033), RAVLT-I (p=0.225), and RAVLT-D (p=0.136) scores. At 6-month follow-up, PD-CTRL showed no significant differences in WOQ-19, motor scales, and neuropsychological tests compared to baseline (Table 1, 2, 3, 4).

Conclusion: OPC improved end-of-dose fluctuations in anxiety, depression, and executive functions/attention, while memory and visuospatial abilities showed no significant changes.

TABLE 3B

TABLE 3A

TABLE 2

TABLE 1

TABLE 4

References: [1]. R. Martínez-Fernández, E. Schmitt, P. Martinez-Martin, P. Krack, The hidden sister of motor fluctuations in Parkinson’s disease: a review on nonmotor fluctuations, Mov. Disord. 31 (2016) 1080-1094, https://doi.org/10.1002/mds.26731.

[2]. M. Fabbri, J.J. Ferreira, A. Lees, F. Stocchi, W. Poewe, E. Tolosa, O. Rascol, Opicapone for the treatment of Parkinson’s disease: a review of a new licensed medicine, Mov. Disord. 33 (2018) 1528-1539, https://doi.org/10.1002/mds.27475.

[3]. J.J. Ferreira, A. Lees, J.F. Rocha, W. Poewe, O. Rascol, P. Soares-da-Silva, Bi-Park 1 investigators, Opicapone as an adjunct to levodopa in patients with Parkinson’s disease and end-of-dose motor fluctuations: a randomised, double-blind, controlled trial, Lancet Neurol. 15 (2016) 154-165, https://doi.org/10.1016/S1474-4422(15)00336-1.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/opicapone-improves-end-of-dose-neuropsychiatric-fluctuations-in-patients-with-parkinsons-disease/