Pharmacogenomic Decision Support With GeneSight Psychotropic to Guide the Treatment of Major Depressive Disorder

The primary objectives of this study are 1) to compare the efficacy of GEN to treatment as usual (TAU) in improving response to psychotropic treatment in outpatients suffering from a MDD and having had - within the current episode - an inadequate response to at least one psychotropic medication included in GEN; and 2) to validate the utility of the new CAMH markers and demonstrate the superior predictive capabilities and greater clinical utility of E-GEN as compared to GEN. This study is designed as a three-arm multi-centre, double-blind (participants and raters), randomized controlled trial to compare the clinical and economic outcomes of GEN, E-GEN and TAU for patients suffering from a MDD and having had - within the current episode - an inadequate response to at least one psychotropic medication included in GEN. Participants will be randomized in a 1:1:1 ratio to each of the three treatment arms. Recruitment will be 24 months. Follow-up will be 12 months. Subjects will complete short diagnostic interviews specific to their clinical diagnosis, basic metabolic measures (eg. blood pressure, weight), and provide buccal swab samples for genetic analysis (the unanalyzed buccal swabs and associated DNA will be biobanked). During the first visit, blood and urine samples will be required for laboratory panel screening and blood biobanking. Subjects will be monitored over a one year period and clinical measures and healthcare resource utilization will be obtained. Treating clinicians in the GEN and E-GEN arms will receive an easy to implement report providing pharmacogenomic guidance for prescribing psychotropic medications to their patients. The study will recruit subjects from 10 sites, stratified into 2 clusters. Nine study sites altogether will form one of the two stratified clusters. CAMH will constitute the tenth study site and the second stratified cluster.The sample size required for this study was calculated using effect size estimates drawn from a previous study conducted by Hall-Flavin et al \[Pharmacogenetics Genomics 2013; 23(10)\]. Assuming an effect size of 0.30 in HAM-D17 score favoring the treatment group, intra class coefficient between clusters of 20%, statistical power of 90%, an alpha level of 0.05, and an expected 16.7% rate of premature discontinuation by Week 8 (primary endpoint), a total of 570 subjects (i.e., 190 per treatment arm) are required to detect the same effect in this study.