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3 The dopaminergic balancing act: a literature review of a novel COMT inhibitor opicapone with a focus on the risk of visual hallucinations
  1. Richard Cole,
  2. Romi Saha
  1. King’s College, London


Aims Parkinson’s Disease (PD) medications are well-evidenced for improving motor symptoms. However, often a balancing act is required to ameliorate positive neuropsychiatric symptoms, such as visual hallucinations (VH). Opicapone, a novel COMT inhibitor, has been shown by BIPARK-1 and BIPARK-2 studies to improve wearing-off phenomena but little is known about associated neuropsychiatric symptoms. The aim of this literature review was to investigate any association between opicapone and VH.

Methods A literature review was undertaken on the 18th July 2019 using PubMed, Ovid (using key resources of Embase, Ovid MEDLINE, Global Health and PsycINFO), Web of Science and Scopus. The search terms used were ‘Parkinson’s Disease’ and ‘Opicapone’. The search included full-texts, abstracts, conference abstracts and posters.

Results The initial search produced 398 articles; 391 were excluded. Of the 7 articles reviewed there were two randomised controlled trials (RCTs) (BIPARK-1 and -2), two observational studies, two post-hoc analyses of BIPARK-1 and -2, and one retrospective analysis. BIPARK-1 reported VH in 1% of the entacapone group, 8% opicapone 25 mg group and 4% of the opicapone 50 mg group. BIPARK-2 did not report on VH in their randomised phased and reported VH in 0.8% of opicapone patients in their open-label phase but without specifying the associated dose.

Chaudhuri et al.’s (2018) post-hoc analysis of BIPARK-1 reported VH in 8% of COMT- naive patients given opicapone, vs. 1% of those given entacapone. Lees et al.’s (2019) post-hoc analysis of BIPARK-1 & -2 reported VH in 4.6% of patients receiving opicapone who were ≥70 years old, vs 0.6% in those younger. Gandor et al.’s (2018) prospective observational study reported VH in 14.8% of patients given opicapone.

Conclusions Several factors limit the conclusions drawn about the risk of VH in patients taking opicapone. The RCTs were designed and powered to assess ‘on-off’ phenomena and didn’t include patients >65 or with a psychiatric history. This also limits their post-hoc analyses’ generalisability. The more ‘real-world’ observational studies were small and only available in abstract form with limited details. Lees et al.’s (2019) post-hoc analysis nevertheless reported a higher incidence of VH in the older age group, which is concordant with known risk factors for neuropsychiatric adverse events. Further investigation is required, focusing on older patients and those with a psychiatric history or cognitive impairment.

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