A new WA-based study aims to improve outcomes in treatment resistant depression. Major Depressive Disorder (MDD) is one of the leading causes of illness and disease burden in Australia. In the 2021 Australian National Health Survey, 8% of people surveyed had experienced a mood (affective) disorder in the previous 12 months.
General practitioners continue to treat the majority of depression in the community, with these disorders associated with significant disability, role impairment and substance use comorbidity.
Antidepressants are used to treat moderate to severe MDD, with 74% of mental health prescriptions provided for antidepressant medication. Current antidepressants are often inadequate as approximately half of patients see no response and two-thirds fail to see remission of symptoms. The process of finding a suitable medication then becomes a trial-and-error approach but the chances of remission and response rates decrease with every subsequent medication trialled.
Treatment Resistant Depression (TRD) is defined as MDD which fails to respond to at least two different antidepressants. Patients with TRD are more likely to have lower remission rates, substantially lower quality of life and higher suicide rates compared to patients with MDD who respond to antidepressant treatment.
Many patients spend years switching from one medication to the next in search of something that works. Finding more innovative and targeted approaches to help those with TRD is a critical unmet need in the health system.
Personalised or ‘precision’ medicine models of care are increasingly effective for achieving better outcomes for the individual patient, instead of using a one-drug-fits-all model. One approach to precision medicine is the use of pharmacogenomics (PG), which involves the study of an individual’s genetic make-up to understand how that influences their body’s ability to metabolise drugs and consequently their response to prescribed medications.
Some of the variation in response rates and frequency of side effects can be attributed to variation in genes involved in the absorption, distribution, metabolism and excretion of specific drugs.
PG support tools provide information relevant for drug selection or dosing decisions and has the potential to guide drug and dose selection to improve patient outcomes. Genetic variants can contribute up to 50% of antidepressant response rates, with a recent meta-analysis of multiple studies showing a significant association between PG-informed prescribing and remission of MDD.
A new WA-based study focuses on the clinical application of PG support tools in treatment resistant depression. The GLAD (Genetics Linked to Antidepressants) trial is recruiting adults with treatment resistant depression and offers free pharmacogenomic testing to participants eligible for the trial. Participants will have psychiatric assessment on screening and regular assessments with the study team throughout the 12-week trial.
The aim of the study is to determine if treatment with pharmacogenomic-informed antidepressant therapy improves clinical outcomes in treatment resistant depression compared with today’s widely adopted ‘trial and error’ approach.
The principal investigator is Professor Sean Hood (head of UWA’s Division of Psychiatry & Sir Charles Gairdner Hospital, North Metropolitan Health Service, WA). The research has ethics approval at the University of WA and registered on ANZCTR.
Apart from the potential benefits of taking part in the trial, participants and their GPs will have access to their pharmacogenetic testing report at the end of the trial to guide the choice and/or dosing of any medications that may be relevant to their current or future treatment(s).
Those who would like to express their interest in participating should email the GLAD study coordinator at gladstudy@uwa.edu.au
Author competing interests – the author is involved in the research described