Title : Precision psychiatry works: Pharmacogenomics improves treatment response in early schizophrenia- RCT evidence
Abstract:
Schizophrenia treatment outcomes vary due to genetic polymorphisms affecting drug metabolism and receptor pharmacodynamics. Pharmacogenomics (PGx) may optimise antipsychotic efficacy, tolerability, and adherence, particularly in drug-naïve patients where first-choice therapy determines long-term trajectory.A prospective, open-label, randomised controlled trial was conducted from March 2024 to November 2025 at AMU involving 80 drug-naïve schizophrenia patients (ICD-11 criteria), randomised 1:1 to PGx-guided therapy vs treatment-as-usual (TAU). Buccal swabs were analysed using a PCR-based multi-gene panel (CYP2D6, CYP1A2, HTR2A) to guide drug selection and dosing. Assessments occurred monthly for 3 months. Total of 76 participants completed follow-up (PGx n=38; TAU n=38). Baseline PANSS scores were comparable. At 3 months, mean percentage PANSS reduction was higher in PGx (84.9%) vs TAU (72.5%). Response rate (≥50% reduction) was greater in PGx (76.3%) vs TAU (57.9%). Medication switch requirement was lower (31.6% vs 65.8%). ADR incidence was lower in PGx (60.5% vs 78.9%) and lower mean chlorpromazine-equivalent dose. Mixed Model for Repeated Measures (MMRM) adjusted for baseline PANSS showed a statistically significant adjusted mean difference of 12.4% improvement in PGx group (p<0.001). Multi-gene PGx-guided antipsychotic selection significantly improves treatment response, reduces switching, and enhances tolerability in drug-naïve schizophrenia. Integration of PGx appears feasible and beneficial in routine psychiatry within low-middle-income settings.
