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Medications to treat psychosis (i.e., antipsychotics) have common and sometimes serious adverse drug reactions and can require several trials before finding a suitable drug and dose. To address this, there is increasing focus on personalizing medicine. Pharmacogenetics investigates how genetic variation influences drug metabolism and response, with recent clinical trials suggesting pharmacogenetic testing can improve remission and reduce adverse drug reactions. Therefore, understanding stakeholder perspectives on acceptability is critical. This pilot study is part of 'GEMS' (Genetics and Environment in Mental Health Study), which investigates pharmacogenetic testing for psychosis. A participant survey, co-created with patients, was completed by 22 patient-participants, and semi-structured interviews were conducted with 11 clinician-participants who had used pharmacogenetic test reports with patients. Both patients and clinicians were generally positive about pharmacogenetics, although clinicians saw this as just one component in the multifactorial process of individualized prescribing. Clinicians and patients both suggested a more user-friendly format of the pharmacogenetic report to enhance patient understanding. Some described the reports as promoting more collaborative care, but this was not universal. Clinicians highlighted both retrospective and prospective value in pharmacogenetics providing more certainty through reducing 'trial-and-error' prescribing. However, accessibility, understanding, and logistics were identified as potential barriers to implementation. Among patients and clinicians who have experienced pharmacogenetic testing to inform antipsychotic prescribing, acceptability is good. There is potential for pharmacogenetics to enhance personalized prescribing, but barriers to widespread implementation remain.

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.