Pharmacogenomics in psychiatry (MEQ)

(i) HLA pairs and ancestry. HLA-B15:02 is strongly associated with carbamazepine-induced SJS/TEN and is more prevalent in many East and Southeast Asian populations; prospective screening with avoidance of carbamazepine in carriers prevented SJS/TEN in Taiwanese programme data. HLA-A31:01 associates with a broader carbamazepine hypersensitivity spectrum, including in European ancestry cohorts. CPIC provides genotype-guided recommendations for carbamazepine and oxcarbazepine. Ancestry informs pre-test probability and labelling emphasis but decisions follow genotype and guideline, not appearance alone.[1][2][3]

(ii) If HLA-B*15:02 positive and drug-naive. Do not start carbamazepine; choose an alternative mood stabiliser or antipsychotic strategy appropriate to her illness; document the allele in allergy/alert systems; counsel that structurally related aromatics may carry cross-risk considerations per specialist guidance; continue lithium optimisation and psychosocial care rather than forcing CBZ.[1][2]

(iii) SLC6A4 commercial report. CPIC 2023 states existing data do not support using SLC6A4 (or HTR2A) genotypes to guide serotonin reuptake inhibitor prescribing. Proprietary red/green bins are not equivalent to single gene–drug CPIC tables. Do not switch a suitable antidepressant solely for SLC6A4; focus on dose, duration, adherence, formulation, and evidence-based next steps. ISPG consensus prioritises CYP2D6/CYP2C19 and HLA over many PD markers.[4][8]

(iv) CYP enzymes and trials. CYP2D6 and CYP2C19 (also CYP2B6 in the 2023 SRI update) inform selected antidepressant dosing/selection. GUIDED reported improved response/remission with combinatorial testing but warrants critical appraisal of algorithm opacity/industry context; PRIME Care showed reduced gene–drug interaction prescribing with modest/time-limited remission effects rather than durable universal superiority.[4][5][6]

(v) TDM and phenoconversion. Plasma levels (AGNP TDM) measure real-world exposure under adherence, organ function, and interactions. Strong CYP2D6 inhibitors (for example paroxetine, fluoxetine, bupropion) can phenoconvert genotypic normal metabolisers toward functional poor-metaboliser exposure — genotype without interaction review is incomplete.[7][4]