O’Neill, J.R. orcid.org/0000-0001-8664-8825, Jameson, A. orcid.org/0000-0002-3248-2302, McLean, S.L. orcid.org/0000-0001-9328-8928 et al. (3 more authors) (2024) A proposal for reducing maximum target doses of drugs for psychosis: Reviewing dose–response literature. Journal of Psychopharmacology, 38 (4). 344 -352. ISSN 0269-8811
Abstract
Background: Presently, there is limited guidance on the maximal dosing of psychosis drugs that is based on effectiveness rather than safety or toxicity. Current maximum dosing recommendations may far exceed the necessary degree of dopamine D2 receptor blockade required to treat psychosis. This may lead to excess harm through cognitive impairment and side effects.
Aims: This analysis aimed to establish guidance for prescribers by optimally dosing drugs for psychosis based on efficacy and benefit.
Methods: We used data from two dose–response meta-analyses and reviewed seven of the most prescribed drugs for psychosis in the UK. Where data were not available, we used appropriate comparison techniques based on D2 receptor occupancy to extrapolate our recommendations.
Results: We found that the likely threshold dose for achieving remission of psychotic symptoms was often significantly below the currently licensed dose for these drugs. We therefore recommend that clinicians are cautious about exceeding our recommended doses. Individual factors, however, should be accounted for. We outline potentially relevant factors including age, ethnicity, sex, smoking status and pharmacogenetics. Additionally, we recommend therapeutic drug monitoring as a tool to determine individual pharmacokinetic variation.
Conclusions: In summary, we propose a new set of maximum target doses for psychosis drugs based on efficacy. Further research through randomised controlled trials should be undertaken to evaluate the effect of reducing doses from current licensing maximums or from doses that are above our recommendations. However, dose reductions should be implemented in a manner that accounts for and reduces the effects of drug withdrawal.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © The Author(s) 2024. This is an open access article under the terms of the Creative Commons Attribution License (CC-BY 4.0), which permits unrestricted use, distribution and reproduction in any medium, provided the original work is properly cited. |
Keywords: | Dopamine; antipsychotic; dosing; reduction; maximum |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) > Leeds Institute of Health Sciences (Leeds) > Academic Unit of Psychiatry and Behavioural Sciences (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 12 Apr 2024 09:56 |
Last Modified: | 12 Apr 2024 09:57 |
Status: | Published |
Publisher: | SAGE Publications |
Identification Number: | 10.1177/02698811241239543 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:211408 |