Pharmacogenomic-Guided Prescribing for Treatment-Resistant Mental Health Conditions in Australian Primary Care: A Single-GP Practice Retrospective Observation of 29 Patients

Abstract

Treatment-resistant mental health conditions are common in primary care and challenging for clinicians. Trial-and-error prescribing can prolong morbidity and increase adverse drug reactions (ADRs). Pharmacogenomic (PGx) testing enables individualised prescribing by identifying gene–drug interactions affecting psychotropic response. Thirty adults with treatment-resistant mental health conditions underwent PGx testing using a commercial panel (one lost to follow-up [n = 29]). Patients received PGx-guided treatment (n = 8) or standard care (n = 21). Phenotypes were assigned per CPIC and DPWG guidelines, with prescribing guided by clinical experience where guidelines were unavailable. Medication histories were reviewed for gene–drug concordance, ADRs, and treatment failures. Clinical improvement at eight weeks was defined as “marked” or “moderate” improvement and/or ADR resolution. Actionable genotypes were common, particularly CYP2D6 (27.5% poor/intermediate drug metabolising phenotype) and CYP2C19 (37.9%). Guideline-actionable gene–drug interactions occurred in 37% of patients, and eleven patients possessed actionable phenotype at multiple loci. Gene–drug interactions were identified in nine patients and guidance was fully implemented in six. Clinical benefit at 8 weeks was achieved in 6/8 patients with genotype-guided changes versus 8/21 receiving standard care. PGx-guided prescribing may support improved antidepressant response and tolerability while reducing trial-and-error prescribing for treatment-resistant patients in primary care.