GLAD Study: Genetics Linked to Anti-Depressants in Adults with Treatment Resistant Depression

INTERVENTION: After informed consent, a single DNA sample using a buccal swab kit will be collected from all participants for pharmacogenomic (PG) testing at the Screening Visit. For participants randomised to the intervention arm, the treatment plan for their antidepressants will be informed by the participant’s PG report ‐ a recommendation for antidepressant prescribing guided by the participants' pharmacogenomic profile in line with TGA recommended doses. The recommendations about antidepressant class and dose are based on Clinical Pharmacogenetics Implementation Consortium (CPIC) and Royal Dutch Pharmacogenetics Working Group (DPWG) international guidelines. All participants will commence treatment within 4 weeks after the Screening visit. Participants will be reviewed at 2, 4 8 and 12 weeks after treatment initiation (Baseline visit). Participant adherence to antidepressant treatment will be reviewed by the Investigators as per standard of care. In addition the Medication Adherence Report Scale (MARS‐5) will be performed. Both groups will be recommended medications that follows current TGA guidelines. CONDITION: Depression; ; Depression Mental Health ‐ Depression PRIMARY OUTCOME: The primary outcome is remission of depressive symptoms defined as change in depressive symptom score measured by Montgomery and Åsperg Depression Rating Scale (MADRS) [Baseline, Week 4, 8, 12 (primary endpoint), 24 from Randomisation ] SECONDARY OUTCOME: Changes in self‐reported depression symptoms as assessed using the 16‐Item Quick Inventory of Depressive Symptomology – Self‐Report (QIDS‐SR) ; [Baseline, Week 4, 8, 12, 24 from Randomisation ] Response to antidepressants, defined as > 50% decrease in MADRS scores assessed using the Montgomery and Åsperg Depression Rating Scale [Baseline, Week 4, 8, 12, 24 from Randomisation ] Tolerability to antidepressant therapy, defined as the difference in Antidepressant Side Effect Checklist score between the pharmacogenomic (PG)‐informed treatment arm and the standard treatment arm[Baseline, Week 4, 8, 12 from Randomisation] INCLUSION CRITERIA: ‐ Age 18 ‐ 70 years ‐ Sufficiently fluent in English ‐ Diagnosed with MDD, either first‐episode or relapsed, on Mini International Neuropsychiatric Interview (M.I.N.I.) 7.0.2 for DMS‐5 criteria ‐ Montgomery and Asberg Depression Rating Scale (MADRS) score of greater than or equal to 20 at Screening and Baseline ‐ Failure of greater than or equal to 2 prior adequate trial of evidenced‐based treatments in the current MDD episode ‐ Willing and able to provide informed consent