Pharmacogenomics in psychiatry — consultant viva

Station structure

Time: 8–10 minutes. Depth: consultant teaching registrar. Expect named guidelines (CPIC), HLA alleles, phenotype language, and one nuanced trial point each for GUIDED and PRIME Care.[1][3][6]

Core questions and model points

1. PK vs PD genes? PK changes exposure (CYP ADME); PD changes receptor/transporter effect. Actionable psychiatry PGx is mostly PK + HLA, not PD colour bins.[1][10]

2. Phenotypes? PM, IM, NM, RM, UM from diplotype/activity score; direction: PM → higher parent levels of many substrates; UM → lower levels/failure risk.[1][2]

3. SSRI CPIC? Hicks 2015 CYP2D6/2C19 SSRI dosing; Bousman 2023 expands CYP2D6/2C19/2B6 and rejects routine SLC6A4/HTR2A use for prescribing.[1][2]

4. HLA-B*15:02? SJS/TEN risk with carbamazepine; avoid if positive and drug-naive; Chen screening prevented cases in Taiwan pathway.[3][4]

5. HLA-A*31:01? Broader CBZ hypersensitivity association including European ancestry (McCormack).[5][3]

6. Phenoconversion? Strong 2D6 inhibitors (paroxetine/fluoxetine/bupropion) can make genotypic NM behave like PM.[1][9]

7. Atomoxetine? CYP2D6-guided dosing/levels (Brown CPIC).[8]

8. Trials? GUIDED: combinatorial testing outcome signals with appraisal caveats; PRIME Care: better gene–drug matching, modest/time-limited remission effects.[6][7]

9. TDM? AGNP levels complement genotype as in vivo phenotype.[9]

10. ISPG? Supports CYP2D6/2C19 selected use + HLA for CBZ/OXC; limited PD panel enthusiasm.[10]

Distinctions that score

Score for separating safety HLA decisions from optional MDD combinatorial panels, drug-naive HLA-positive starts from already long-term tolerant patients, and report interpretation as star allele → phenotype → drug-specific action rather than algorithm worship.[1][3][10]

Common fails

Fails include mandating every gene before every antidepressant, claiming SLC6A4 short allele means SSRIs never work, asserting negative HLA-B*15:02 means zero rash risk, and confusing CYP1A2 smoking–clozapine interactions with mandatory genotyping-first for all clozapine starts.[1][3][10]