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Effect of CYP1A2, CYP2D6, and CYP3A4 Variation on Antipsychotic Treatment Outcomes

Shranjeno v:
izdano v:Pharmaceuticals vol. 18, no. 6 (2025), p. 892-919
Glavni avtor: Varney, Lauren
Drugi avtorji: Murtough, Stephen, Cotic Marius, Abidoph Rosemary, Chan, Lian, Saadullah Khani Noushin, Richards-Belle, Alvin, Richards-Brown, Maria, Mills, Daisy, Panconesi Daniele, Dawda Yogita, Sharma, Parveen, Shah, Chetan, Secchi Agostina, Nilforooshan Ramin, Mudholkar Santosh, Murdoch, Rosie, Molai Jazmin, Griffiths, Rebecca, Senthilkumar Suruthy, Blake, Helen, Lankshear, Steve, McRoberts, Jennifer, Pastor, Bethany, Carmel, Thomas, Richards, Sabrina, Welfare-Wilson, Alison, Sai-Bo, Cheung, Cox, Rebecca, Jibero, Anita Chinazam, Anad Reanne, Laczik Rebeka, Ghali Sharif, Berry, Alex J, Curwen, Joanna, Koye, Odutoye, Kottalgi Girija, Williams, Sally, Wong, Solomon, Anandan Nithya, Pius Georgy, Ajiteru Tonye, Clark, Victoria, van Driel Philip, Bashir Amir, Court, Samantha, Pawsey Minerva, Skowronska Anna, Woodley, Jessica, Bramon Elvira
Izdano:
MDPI AG
Teme:
Food & Drug Administration > FDA
United Kingdom > UK
Quality of life
Schizophrenia
Mental disorders
Psychotropic drugs
Psychosis
Side effects
Mental depression
Licenses
Bipolar disorder
Metabolism
Mental health
Ethnicity
Genes
Enzymes
Antipsychotics
Clinical outcomes
Drug dosages
Online dostop:Citation/Abstract
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Resumen: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.
ISSN:1424-8247
DOI:10.3390/ph18060892
Fuente:Research Library