{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T12:28:54Z","timestamp":1786969734287,"version":"build-2736575974"},"reference-count":27,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T00:00:00Z","timestamp":1786924800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>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\u2013drug 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\u2013drug concordance, ADRs, and treatment failures. Clinical improvement at eight weeks was defined as \u201cmarked\u201d or \u201cmoderate\u201d 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\u2013drug interactions occurred in 37% of patients, and eleven patients possessed actionable phenotype at multiple loci. Gene\u2013drug 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.<\/jats:p>","DOI":"10.3390\/ijms27167329","type":"journal-article","created":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T12:01:26Z","timestamp":1786968086000},"page":"7329","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Pharmacogenomic-Guided Prescribing for Treatment-Resistant Mental Health Conditions in Australian Primary Care: A Single-GP Practice Retrospective Observation of 29 Patients"],"prefix":"10.3390","volume":"27","author":[{"given":"Cristina","family":"Beer","sequence":"first","affiliation":[{"name":"Centre for Genomics and Personalised Health, School of Biomedical Sciences, Faculty of Health, Queensland University of Technology, Kelvin Grove, QLD 4059, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-9276-0076","authenticated-orcid":false,"given":"Fiona","family":"Rae","sequence":"additional","affiliation":[{"name":"Centre for Genomics and Personalised Health, School of Biomedical Sciences, Faculty of Health, Queensland University of Technology, Kelvin Grove, QLD 4059, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikayla","family":"Watt","sequence":"additional","affiliation":[{"name":"Dr. Cris Medical Services, Robina, QLD 4226, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2084-4986","authenticated-orcid":false,"given":"Annalese","family":"Semmler","sequence":"additional","affiliation":[{"name":"School of Clinical Sciences, Faculty of Health, Queensland University of Technology, Kelvin Grove, QLD 4059, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6645-6164","authenticated-orcid":false,"given":"Joanne","family":"Voisey","sequence":"additional","affiliation":[{"name":"Centre for Genomics and Personalised Health, School of Biomedical Sciences, Faculty of Health, Queensland University of Technology, Kelvin Grove, QLD 4059, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"GBD 2019 Mental Disorders Collaborators (2022). Global, regional, and national burden of 12 mental disorders in 204 countries and territories, 1990\u20132019: A systematic analysis for the global burden of disease study 2019. Lancet Psychiatry, 9, 137\u2013150.","DOI":"10.1016\/S2215-0366(21)00395-3"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1002\/wps.20941","article-title":"The efficacy of psychotherapies and pharmacotherapies for mental disorders in adults: An Umbrella Review and Meta-analytic evaluation of recent Meta-analyses","volume":"21","author":"Leichsenring","year":"2022","journal-title":"World Psychiatry"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"545","DOI":"10.31887\/DCNS.2014.16.4\/spreskorn","article-title":"Prediction of individual response to antidepressants and antipsychotics: An integrated concept","volume":"16","author":"Preskorn","year":"2014","journal-title":"Dialogues Clin. Neurosci."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1071\/HC23168","article-title":"Patient demographics and psychotropic medication prescribing in Australian general practices: Pre- and during COVID-19 pandemic","volume":"16","author":"Kibret","year":"2024","journal-title":"J. Prim. Health Care"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1002\/cpt.2350","article-title":"An evidence-based framework for Evaluating Pharmacogenomics Knowledge for Personalized Medicine","volume":"110","author":"Huddart","year":"2021","journal-title":"Clin. Pharmacol. Ther."},{"key":"ref_6","unstructured":"RCPA (2026, March 26). Pharmacogenomic Indications in Australia. n.d. Available online: https:\/\/www.rcpa.edu.au\/Library\/Practising-Pathology\/Pharmacogenomic-Indications-in-Australia."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1002\/cpt.70006","article-title":"Insights into patient-level exposure to actionable pharmacogenomic medications in Australia using a new national pharmacogenomic guideline","volume":"119","author":"Ianni","year":"2025","journal-title":"Clin. Pharmacol. Ther."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"662","DOI":"10.1038\/clpt.2011.34","article-title":"Pharmacogenetics: From bench to byte\u2014An update of guidelines","volume":"89","author":"Swen","year":"2011","journal-title":"Clin. Pharmacol. Ther."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1038\/s41380-021-01200-3","article-title":"Treatment resistance in psychiatry: State of the art and New Directions","volume":"27","author":"Howes","year":"2021","journal-title":"Mol. Psychiatry"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"e063095","DOI":"10.1136\/bmjopen-2022-063095","article-title":"What are the treatment remission, response and extent of improvement rates after up to four trials of antidepressant therapies in real-world depressed patients? A reanalysis of the STAR*D study\u2019s patient-level data with fidelity to the original research protocol","volume":"13","author":"Pigott","year":"2023","journal-title":"BMJ Open"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Lorvellec, M.-A., Sipahimalani, G., Lahutte, B., Delacour, H., Baldacci, A., and Saguin, E. (2024). Pharmacogenetics testing for poor response to antidepressants: A transnosographic case series. Front. Pharmacol., 15.","DOI":"10.3389\/fphar.2024.1440523"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Tesfamicael, K.G., Zhao, L., Fern\u00e1ndez-Rodr\u00edguez, R., Adelson, D.L., Musker, M., Polasek, T.M., and Lewis, M.D. (2024). Efficacy and safety of pharmacogenomic-guided antidepressant prescribing in patients with depression: An Umbrella Review and updated meta-analysis. Front. Psychiatry, 15.","DOI":"10.3389\/fpsyt.2024.1276410"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/j.jpsychires.2019.01.003","article-title":"Impact of pharmacogenomics on Clinical Outcomes in major depressive disorder in the guided trial: A large, patient- and rater-blinded, randomized, controlled study","volume":"111","author":"Greden","year":"2019","journal-title":"J. Psychiatr. Res."},{"key":"ref_14","unstructured":"The Royal College of Pathologists of Australiasia (2026, March 26). Position Statement Subject: Utilisation of Pharmacogenetics in Healthcare. Available online: https:\/\/www.rcpa.edu.au\/Library\/College-Policies\/Position-Statements\/Utilisation-of-pharmacogenetics-in-healthcare."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"510","DOI":"10.5694\/mja2.51759","article-title":"Pharmacogenomics in the era of personalised medicine","volume":"217","author":"White","year":"2022","journal-title":"Med. J. Aust."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1114","DOI":"10.1038\/s41431-021-01004-7","article-title":"Dutch Pharmacogenetics Working Group (DPWG) guideline for the gene-drug interaction between CYP2C19 and CYP2D6 and ssris","volume":"30","author":"Brouwer","year":"2021","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Daly, A.K., Rettie, A.E., Fowler, D.M., and Miners, J.O. (2017). Pharmacogenomics of CYP2C9: Functional and clinical considerations. J. Pers. Med., 8.","DOI":"10.3390\/jpm8010001"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.ibror.2019.01.001","article-title":"The emergence of new antidepressants for clinical use: Agomelatine paradox versus other novel agents","volume":"6","author":"Fasipe","year":"2019","journal-title":"IBRO Rep."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1177\/0269881119827959","article-title":"Polymorphisms in CYP1A2, cyp2c9 and abcb1 affect agomelatine pharmacokinetics","volume":"33","author":"Ochoa","year":"2019","journal-title":"J. Psychopharmacol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1124\/jpet.111.183111","article-title":"Polymorphic variants of cytochrome P450 2B6 (CYP2B6.4\u2013CYP2B6.9) exhibit altered rates of metabolism for bupropion and Efavirenz: A charge-reversal mutation in the K139E variant (CYP2B6.8) impairs formation of a functional cytochrome P450-reductase complex","volume":"338","author":"Zhang","year":"2011","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_21","unstructured":"North West Genomic Medicine Service Alliance (2026, March 26). Spotlight: PROGRESS Pharmacogenomics Project. NHS Choices. Available online: https:\/\/www.nw-gmsa.nhs.uk\/about-us\/our-projects\/spotlight."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1038\/s41588-022-01274-x","article-title":"The Singapore National Precision Medicine Strategy","volume":"55","author":"Wong","year":"2023","journal-title":"Nat. Genet."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"137","DOI":"10.2217\/pgs-2020-0173","article-title":"Veterans Affairs pharmacogenomic testing for veterans (phaser) clinical program","volume":"22","author":"Dong","year":"2021","journal-title":"Pharmacogenomics"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Kennedy, A., Scodellaro, S., Verstegen, R.H., and Cohn, I. (2025). Pharmacogenetic testing of children and adolescents with mental health conditions: Real-world experiences. Pharmaceuticals, 18.","DOI":"10.3390\/ph18081170"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1093\/pch\/pxae029","article-title":"Gene-based drug therapy for children and youth treated with psychoactive medications","volume":"29","author":"Verstegen","year":"2024","journal-title":"Paediatr. Child Health"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1298","DOI":"10.1111\/cts.12830","article-title":"CYP2C19 allele frequencies in over 2.2 million direct-to-consumer genetics research participants and the potential implication for prescriptions in a large health system","volume":"13","author":"Ionova","year":"2020","journal-title":"Clin. Transl. Sci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"773","DOI":"10.2165\/00002018-200427110-00003","article-title":"Drug interactions with St John\u2019s Wort","volume":"27","author":"Mannel","year":"2004","journal-title":"Drug Saf."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/16\/7329\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T12:11:04Z","timestamp":1786968664000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/16\/7329"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,17]]},"references-count":27,"journal-issue":{"issue":"16","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["ijms27167329"],"URL":"https:\/\/doi.org\/10.3390\/ijms27167329","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,17]]}}}