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Yet, the tolerability and efficacy of antidepressant drugs in youth remain poor. Pharmacogenetic (PGx) testing, or the personalised and guided treatment of medication based on genetic data, has been suggested to improve the effectiveness and tolerability of antidepressants. However, limited studies have evaluated the utility of antidepressant PGx-guided treatment in adolescent and young adult populations. Thus, this pilot randomised controlled trial (RCT), the GENE-YD Study, will evaluate the feasibility for a large-scale RCT assessing the effect of PGx-guided antidepressant prescription vs treatment as usual in youth with major depressive disorder (MDD).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and analysis<\/jats:title>\n                    <jats:p>Eighty young people between 16 and 24 years of age and in the early stages of pharmacotherapy treatment for MDD will be recruited. Following initial screening, participants will be randomised on a 1:1 ratio to either the intervention or control study group. Participants in the intervention condition will have their treatment tailored based on their PGx profile. Participants randomised into the control group will have their prescription based on current best practice recommendations, or treatment as usual. Individuals will be assessed at drug prescription baseline and again 6 and 12\u2009weeks following drug prescription. The primary outcome of the study will be to evaluate the feasibility and acceptability of the GENE-YD protocol. Specifically, this study will explore participation recruitment strategies and attrition to the study protocols to guide the recruitment processes of a large-scale RCT, along with participating satisfaction in overall study protocols. Secondary outcomes will inform the utility and variability of specific measures (eg, depression rating scales, quality of life measures and medication adherence scales) that may be scaled up for use in a future full-scale trial.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Ethics and dissemination<\/jats:title>\n                    <jats:p>Ethics approval was granted by the Department of Health, Western Australia\u2019s Human Research Ethics Committee (RGS0000006822) and recognised by the University of Western Australia\u2019s Human Research Ethics Committee (2024\/ET000685). All participants will be required to provide written informed consent. Results will be published in international peer-reviewed journals.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration number<\/jats:title>\n                    <jats:p>ACTRN12624000760572.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjopen-2025-103644","type":"journal-article","created":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T11:46:13Z","timestamp":1762861573000},"page":"e103644","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":1,"title":["PharmacoGENEtics in Youth Depression (GENE-YD) Study protocol: a pilot triple-blinded randomised controlled trial using pharmacogenetics to tailor antidepressant treatment in young 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