A systematic review of the cognitive effects of the COMT inhibitor, tolcapone, in adult humans

Abstract

Objective: the catechol-o-methyltransferase (COMT) inhibitor tolcapone constitutes a potentially useful probe of frontal cortical dopaminergic function. The aim of this systematic review was to examine what is known of effects of tolcapone on human cognition in randomised, controlled studies.

Methods: the study protocol was pre-registered on the Open Science Framework (OSF). A systematic review was conducted using PubMed to identify relevant randomised controlled trials examining effects of tolcapone on human cognition. Identified articles were then screened against inclusion and exclusion criteria.

Results: of 22 full text papers identified, 13 randomised control trials were found to fit the pre-specified criteria. The most consistent finding was that tolcapone modulated working memory – however, the direction of effect appeared to be contingent on the COMT polymorphism (more consistent evidence of improvement in Val-Val participants). There were insufficient nature and number of studies for meta-analysis.

Conclusion: the cognitive improvements identified upon tolcapone administration, in some studies, are likely to be due to the level of dopamine in the prefrontal cortex being shifted closer to its optimum, per an inverted U model of prefrontal function. However, results should be interpreted cautiously due to the small numbers of studies. Given the centrality of cortical dopamine to understanding human cognition, studies using tolcapone in larger samples and across a broader set of cognitive domains would be valuable. It would also be useful to explore effects of different dosing regimens (different doses; and single versus repeated administration).

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Identifiers

ORCID for S.R. Chamberlain: orcid.org/0000-0001-7014-8121

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