A systematic review of the cognitive effects of the COMT inhibitor, tolcapone, in adult humans
A systematic review of the cognitive effects of the COMT inhibitor, tolcapone, in adult humans
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 randomized controlled studies. Methods The study protocol was preregistered on the Open Science Framework. A systematic review was conducted using PubMed to identify relevant randomized controlled trials examining the effects of tolcapone on human cognition. Identified articles were then screened against inclusion and exclusion criteria. Results Of the 22 full-text papers identified, 13 randomized 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, the 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 the effects of different dosing regimens (different doses; and single versus repeated administration).
COMT inhibitor, Tolcapone, catechol-o-methyltransferase inhibitor, cognition, dopamine, enhancement
166-175
Kings, Emilia
d892b141-58ee-4b3a-a716-c76696f24da6
Ioannidis, K.
82240a24-3153-45bb-bfaf-c6df9cd4f261
Grant, J.E.
07372bd5-8a0d-42b4-b41b-e376c652acf3
Chamberlain, S.R.
8a0e09e6-f51f-4039-9287-88debe8d8b6f
15 March 2024
Kings, Emilia
d892b141-58ee-4b3a-a716-c76696f24da6
Ioannidis, K.
82240a24-3153-45bb-bfaf-c6df9cd4f261
Grant, J.E.
07372bd5-8a0d-42b4-b41b-e376c652acf3
Chamberlain, S.R.
8a0e09e6-f51f-4039-9287-88debe8d8b6f
Kings, Emilia, Ioannidis, K., Grant, J.E. and Chamberlain, S.R.
(2024)
A systematic review of the cognitive effects of the COMT inhibitor, tolcapone, in adult humans.
CNS Spectrums, 29 (3), .
(doi:10.1017/S1092852924000130).
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 randomized controlled studies. Methods The study protocol was preregistered on the Open Science Framework. A systematic review was conducted using PubMed to identify relevant randomized controlled trials examining the effects of tolcapone on human cognition. Identified articles were then screened against inclusion and exclusion criteria. Results Of the 22 full-text papers identified, 13 randomized 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, the 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 the effects of different dosing regimens (different doses; and single versus repeated administration).
Text
EM.Project Report CNS
- Accepted Manuscript
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Accepted/In Press date: 11 March 2024
e-pub ahead of print date: 15 March 2024
Published date: 15 March 2024
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For the purpose of open access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission.
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© 2024 Cambridge University Press. All rights reserved.
Keywords:
COMT inhibitor, Tolcapone, catechol-o-methyltransferase inhibitor, cognition, dopamine, enhancement
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Local EPrints ID: 488185
URI: http://eprints.soton.ac.uk/id/eprint/488185
ISSN: 1092-8529
PURE UUID: 1309590b-397e-4074-9242-fab22dc8ec40
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Date deposited: 18 Mar 2024 17:30
Last modified: 30 Aug 2024 02:00
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Author:
Emilia Kings
Author:
K. Ioannidis
Author:
J.E. Grant
Author:
S.R. Chamberlain
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