An Australian Multicentre Double-Blinded Randomised Controlled Trial of Genotype-guided versus Standard Psychotropic Therapy in Moderately-to-Severely Depressed Patients Initiating Pharmacotherapy

Depression is a serious and prevalent illness that remains one of the leading causes of morbidity and disease burden worldwide, including
Australia. Current pharmacotherapy for Major Depressive Disorder (MDD) lacks precision, with medication selection and dosing decision being
primarily based on empirical choice and sequential medication trial-and-error. About two-thirds of patients with moderate-to-severe MDD fail to
achieve remission following first-line medication. In these non-remitters the chance of remission diminishes with every medication trial-anderror
iteration. There is a pressing and largely unmet need for precision approaches. This application aims to exploit recent advances in
pharmacogenomics and neuroimaging biomarkers to develop a more effective precision approach to treatment selection. Informed by consumers,
and partnering with public/private health services, this proposal will address current evidence gaps in PG, incorporating a comprehensive
economic evaluation of PG-guided care versus standard care, investigate the incremental benefit of neuroimaging to PG, and combine clinical,
PG, and neuroimaging data via Deep Learning to develop a user-friendly decision support tool. Built upon prior initiatives, this project has
scalability and aims to reduce barriers to clinical uptake of PG. It will help to build a value for money mental health service, by generating
economic data to substantiate a potential application to the Medical Services Advisory Committee for public funding of mental health PG to
guide treatment of MDD.