By Mr Bradley Roberts, Perron Institute & UWA, and Professor Sean Hood, Perron Institute, UWA and SCGH
Researchers at the Perron Institute for Neurological and Translational Science have recently launched the GENE-YD study, an innovative trial exploring the benefits of pharmacogenetic testing to optimise antidepressant pharmacotherapy in young Western Australians.
This pilot randomised controlled trial aims to explore the feasibility for a larger trial in WA to improve treatment outcomes through personalising patients’ antidepressant prescriptions, helping young people achieve symptom relief faster with fewer medication-related side effects.
Major Depressive Disorder (MDD) is among the leading causes of disability in Australian youth, with a rising number of young people seeking treatment and support for their mental health each year.
Antidepressants are often a first-line treatment for those suffering from moderate to severe depression, and with the prevalence of MDD rising so too are prescription and consumption rates of antidepressant medications.
Between 2015 and 2019, antidepressant use increased by 16% in Australians aged 10-24 years – a rate likely to have climbed further since the COVID-19 pandemic.
GPs are at the coalface of MDD treatment with over 85% of antidepressant medications prescribed in primary care settings. These medications are often prescribed using a clinical trial-and-error approach, with adjustments based on patient initial response or side effect presentation.
This process can be particularly challenging for young people, who may become discouraged by unsuccessful attempts to find the right medication, often choosing to cease treatment without informing their mental healthcare professionals, friends, or family.
The traditional antidepressant prescription model has been associated with a reduction in antidepressant treatment response by up to 20% come the second drug trial and up to 32% come the third and fourth.
Furthermore, the likelihood for symptom remission drops to 14% when patients start their third antidepressant drug trial, with side effects presentation more likely with each subsequent medication.
Given these limitations, new methods of prescription are required to ensure all young people exploring antidepressant medication are given the best chance for a therapeutic outcome.
Pharmacogenetics, or PGx, is the study and application of how common genetic variance may influence the way in which we metabolise and respond to drugs.
By understanding the variance in key genetic markers, clinicians may be better informed on medications and doses best suited to individual patients, potentially shortening the time to symptom relief and reducing the need for multiple drug trials.
PGx testing requires the collection of a DNA sample, often via a simple cheek swab, to identify and characterise genetic markers associated with drug metabolism.
RELATED: Gene testing for meds
For antidepressants, drug-metabolising enzymes such as CYP2D6 and CYP2C19 play critical roles in how individuals process medications.
Simply put, an upregulation of these genes may result in metabolising drugs quickly, reducing antidepressant efficacy. Alternatively, metabolising drugs slowly due to a downregulation of these genes may result in increased risk of drug toxicity and medication-related side effect presentation.
PGx testing reveals these insights prior to treatment commencement, guiding informed prescription decisions.
Key messages
- A new WA trial is investigating the utility of genetic testing to improve treatment outcomes in youth depression
- Genetic markers for drug metabolism are being evaluated to optimise antidepressant pharmacotherapy and provide more personalised care
- The GENE-YD study is actively recruiting people aged 16-24 years with a history of MDD who are seeking antidepressant treatment.
In the Perron Institute GENE-YD study, WA researchers are taking a pre-emptive approach to PGx-informed care, investigating how proactive PGx testing in the early stages of mental healthcare impacts antidepressant response and treatment outcomes in young people with MDD.
The GENE-YD study is actively recruiting up to 80 participants aged 16-24 years who have been diagnosed with MDD and are considering either starting or adjusting their antidepressant prescription.
Participants in the study will undergo a PGx test to identify specific genetic markers linked to antidepressant response.
This will allow the research team to provide participants’ GPs with an antidepressant treatment guide, written by psychiatrist and GENE-YD Chief Investigator, Professor Sean Hood.
The goal of the GENE-YD study is to improve the efficacy of antidepressant pharmacotherapy for young people suffering MDD.
By using PGx screening to identify optimal treatment plans, we hope to increase the likelihood of achieving symptom relief with the first prescribed medication.
This trial also aims to assess the utility of PGx in reducing medication-related side effects, improving medication adherence and quality of life.
As the GENE-YD study is a pilot trial, results and participant feedback will help to inform a larger RCT to further explore the use of PGx in youth psychiatric primary care.
ED: For more information, email the Perron Institute PGx research team on PGx@perron.uwa.edu.au or visit www.perroninstitute.org/clinics/clinical-trials/youth-mental-health-gene-yd-project
Author competing interests – the authors are involved in the study.
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