Journal Article

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

Pawsey, Minerva, Bramon, Elvira, Laczik, Rebeka, Pastor, Bethany, Lankshear, Steve, Anad, Reanne, Mills, Daisy, Blake, Helen, Murtough, Stephen, Richards, Sabrina, Saadullah Khani, Noushin, Cox, Rebecca, Abidoph, Rosemary, Odutoye, Koye, Shah, Chetan, Secchi, Agostina, Mudholkar, Santosh, Richards-Belle, Alvin, Woodley, Jessica, van Driel, Philip, Chan, Lian, Jibero, Anita Chinazam, Kottalgi, Girija, Clark, Victoria, Ajiteru, Tonye, Williams, Sally, Cheung, Sai-Bo, Dawda, Yogita, Anandan, Nithya, McRoberts, Jennifer, Cotic, Marius, Court, Samantha, Ghali, Sharif, Wong, Solomon, Molai, Jazmin, Varney, Lauren, Skowronska, Anna, Bashir, Amir, Richards-Brown, Maria, Senthilkumar, Suruthy, Berry, Alex J., Panconesi, Daniele, Thomas, Carmel, Nilforooshan, Ramin, Griffiths, Rebecca, Murdoch, Rosie, Welfare-Wilson, Alison, Pius, Georgy, Sharma, Parveen, Curwen, Joanna

2025

Overview

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.

• Publisher: MDPI AG,MDPI
• Subject: Adverse and side effects / Antipsychotic drugs / Antipsychotics / Bipolar disorder / Clinical outcomes / Complications and side effects / CYP1A2 / CYP2D6 / CYP3A4 / Cytochrome P-450 / Drug dosages / Drug metabolism / Drugs / Enzymes / Ethnicity / Genes / Genetic aspects / Genetic variation / Health aspects / Licenses / Mental depression / Mental disorders / Mental health / Metabolism / Patient outcomes / pharmacogenetics / Physiological aspects / Psychosis / Psychotropic drugs / Quality of life / Schizophrenia / Side effects