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

**Authors:** Roberta De Fiores, Iolanda Martino, Andrea Quattrone, Basilio Vescio, Gennarina Arabia, Antonio Gambardella, Maurizio Morelli

PMC · DOI: 10.1016/j.prdoa.2025.100343 · Clinical Parkinsonism & Related Disorders · 2025-05-07

## TL;DR

Opicapone, a drug used for Parkinson's disease, helps reduce neuropsychiatric symptoms like anxiety and attention issues that occur as the medication wears off.

## Contribution

This study demonstrates that Opicapone improves non-motor symptoms like anxiety and executive functions in Parkinson’s patients during end-of-dose fluctuations.

## Key findings

- Opicapone significantly improved anxiety, mood, and executive functions in Parkinson’s patients after six months.
- No significant changes in memory or visuospatial abilities were observed with Opicapone treatment.
- Control group patients showed no improvement in neuropsychiatric or motor symptoms over six months.

## Abstract

•Non-motor fluctuations are debilitating complications in levodopa-treated PD patients.•End-of-dose neuropsychiatric symptoms are the most common non-motor fluctuations.•Opicapone is a COMT inhibitor indicated for end-of-dose motor fluctuations.•Opicapone improves fluctuations in anxiety/mood and executive functions/attention.•Opicapone is useful for the management of neuropsychiatric fluctuations in PD.

Non-motor fluctuations are debilitating complications in levodopa-treated PD patients.

End-of-dose neuropsychiatric symptoms are the most common non-motor fluctuations.

Opicapone is a COMT inhibitor indicated for end-of-dose motor fluctuations.

Opicapone improves fluctuations in anxiety/mood and executive functions/attention.

Opicapone is useful for the management of neuropsychiatric fluctuations in PD.

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.

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.

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; FAS, p < 0.001; FAB, 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.

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

## Linked entities

- **Chemicals:** Opicapone (PubChem CID 135565903)
- **Diseases:** Parkinson’s disease (MONDO:0005180)

## Full-text entities

- **Genes:** COMT (catechol-O-methyltransferase) [NCBI Gene 1312] {aka HEL-S-98n}
- **Diseases:** PD (MESH:D010300), anxiety (MESH:D001007), depression (MESH:D003866)
- **Chemicals:** levodopa (MESH:D007980), OPC (MESH:C549349)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

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## References

33 references — full list in the complete paper: https://tomesphere.com/paper/PMC12141878/full.md

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Source: https://tomesphere.com/paper/PMC12141878