Effect of CYP1A2, CYP2D6, and CYP3A4 Variation on Antipsychotic Treatment Outcomes
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Authors
Varney, Lauren
Murtough, Stephen
Cotic, Marius
Ahidoph, Rosemary
Chan, Lian
Khani, Noushin Saadullah
Richards-Belle, Alvin
Richards-Brown, Maria
Mills, Daisy
Panconesi, Daniele
Issue Date
2025-06-14
Type
Article
Language
en
Keywords
Wessex Classification Subject Headings::Psychology , Wessex Classification Subject Headings::Pharmacology
Alternative Title
Abstract
Background/Objectives: Antipsychotic treatment response varies considerably between individuals, with one potential reason being genetic variation affecting the cytochrome P450 enzymes that metabolise them. Methods: With a diverse sample of 453 participants, we studied the influence of CYP1A2, CYP2D6, and CYP3A4 variation on three antipsychotic treatment outcomes: participant-reported adverse antipsychotic drug reactions, health-related quality of life, and the dose of antipsychotic medication prescribed. These measures were taken from the baseline assessment, before a pharmacogenetic intervention was delivered. Results: Over half of our sample (62.9%) were carriers of an allele associated with altered metabolism of antipsychotic medications on CYP2D6 or CYP3A4, the two genes with pharmacogenetic guidelines for antipsychotic medications. Ultrarapid CYP2D6 metabolisers reported significantly lower levels of adverse antipsychotic drug reactions than normal CYP2D6 metabolisers (mean difference: −11.1; 95% confidence interval [CI]: −18.9, −3.3; p = 0.00575). There was also suggestive evidence of lower quality of life scores in those carrying one (mean difference: −0.0863; 95% CI: −0.1806, 0.0081; p = 0.0731) or two copies (mean difference: −0.0803; 95% CI: −0.1734, 0.0129; p = 0.0914) of the CYP1A2*30-inducible allele. Conclusions: Our findings suggest that even when looking at a small number of cytochrome P450 genes, carrying an allele associated with altered antipsychotic medication metabolism is relatively common. We also found evidence that the CYP genotype can influence antipsychotic treatment outcomes, specifically adverse drug reactions and quality of life scores.
Description
© 2025 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Citation
Varney, L. et al. (2025) 'Effect of CYP1A2, CYP2D6, and CYP3A4 Variation on Antipsychotic Treatment Outcomes', Pharmaceuticals, 18(6) 892. Available at: https://doi.org/10.3390/ph18060892
Publisher
MDPI
License
Journal
Volume
Issue
PubMed ID
ISSN
1424-8247