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The Living with Anxiety study aims to identify genes that influence a person’s risk of developing anxiety disorders and genes that impact how well treatments for anxiety work.
Anxiety disorders are the most common mental problems in Australia, with 1 in 6 adults experiencing an anxiety disorder in any given year. Anxiety disorders co-occur with other disabling conditions, most commonly depression. As noted in the 2024 Health of the Nation report, anxiety and depressive disorders are among the most common reasons for patients to seek help from a general practitioner.
While anxiety disorders are often first, and optimally, treated with psychological therapies, antidepressants are also commonly prescribed. Although medication can be an effective second line or concurrent treatment strategy, it can take some time and effort to optimise treatment. This is due, in part, to a range of adverse reactions, including initially headache, nausea, vomiting, agitation or sleep difficulties, and later problems like weight gain or sexual dysfunction. It has been estimated that up to 20% of individuals using antidepressants will experience at least one distressing side effect, and these difficulties are a major cause of medication discontinuation.
The role of pharmacogenomics
Pharmacogenomics tests may aid initial selection of the most efficacious medications with the lowest chance of adverse drug reactions. It is, in many ways, the operationalisation of precision medicine, and a growing number of pharmacogenomic effects are being identified.
The Clinical Pharmacogenetics Implementation Consortium (CPIC) has developed a series of Clinical Practice Guidelines including for the two most commonly prescribed classes of antidepressants: selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants (TCAs). However, as the position statement from the Royal College of Pathologists of Australia (RCPA) notes, while pharmacogenomics guidance is included on more than 15% of medications in the US, there is “little evidence these developments are being included in Australian health care”.
A 2019 retrospective analysis of 52 000 individuals from the Estonian Biobank found that of those who had been prescribed an antidepressant, up to 65% had genotypes that meant they were likely non-responders. As such, they might have received an alternate medication or dosage if pharmacogenomics-informed prescribing had been implemented. These results highlight the impact that pharmacogenomics-informed prescribing may have, if it were more widely adopted in Australia.
In 2024, RCPA launched a living resource document providing guidance on pharmacogenomic testing, which presents guidelines according to the strength of indication. Notably, a number of commonly prescribed antidepressants are listed in this document as having tests available, and being associated “with adverse effects or therapeutic failure”, but there was a lack of international consensus “regarding indications testing“.
As interest in pharmacogenomics continues to grow, there is also an increasing focus on implementation and the cost effectiveness of these tests. While pharmacogenetic cost effectiveness is an active research focus, very few analyses have been conducted in Australia.
Evidence for the impact of genetic variants on the efficacy and side effects associated with medications is aggregated within PharmGKB. Most of these results come from relatively small studies, with a median sample size of 131, which can be problematic, as many of the genetic variants included in pharmacogenomics tests are often seen in less than 5% of the population. In addition, as many of these results come from clinical trials, the participants who are eligible to participate in these studies, may not represent the Australian community in terms of the rate of co-occurring conditions.
Hence, there is a pressing need to conduct large studies, including participants with common patterns of co-occurring conditions, that also better reflect the Australian population. In other words, much more fine-grained and highly personalised research is urgently needed. To address this issue, we are launching the Living with Anxiety study.
The Living with Anxiety study
The Living with Anxiety study, which is funded by the National Health and Medical Research Council (NHMRC), focuses on Australian adults who have experienced an anxiety disorder. The study acknowledges the complexity of mental health challenges, and welcomes participants who live with co-occurring mental health conditions, most notably, depressive disorders. It has been our experience with related studies in depression and bipolar disorder (here and here) that Australians are very keen to volunteer for such genetic studies. This often surprises many clinicians who assume (wrongly) that those who live with these conditions, or have seen them in other family members, may be reluctant to engage in this style of research.
Participants complete online questionnaires that focus on personal experiences with treatment benefits, medication types and side effects. They also answer questions on their current circumstances, and other health and lifestyle factors that may influence their response to psychological or medical interventions. Participants are then invited to provide a saliva sample using a kit that will be sent by mail, to enable DNA extraction and pharmacogenomic analyses. What this study aims to do, just like the concurrent studies in depression and bipolar disorder, is to not primarily decode the genetic risk factors for these complex conditions, but rather, deliver practical insights into what genetic or environmental factors may predict individual responses (benefits or side effects) to common interventions.
Genome-wide associations studies (GWAS) have been previously conducted to investigate the genes involved in other condition such as anorexia nervosa (ANGI), depression, bi-polar disorder and eating disorders (EDGI). In fact, EDGI follows the ground-breaking advances made through the collaborative ANGI study, in which researchers, including the EDGI team, identified both psychiatric and metabolic causes for anorexia nervosa.
The Living with Anxiety study has the potential to help Australians with common anxiety or depressive disorders, to access better estimates of the potential benefits of pharmacogenomic testing on predicting individual responses to antidepressant medications. It will also help our governments to make key decisions about the longer term value of providing Medicare-based funding of such tests. The long term aim is to help streamline the process of finding optimal treatments for all Australians living with anxiety, and co-occurring conditions.
Should you have a patient aged 18+ years who has been diagnosed with, and treated for an anxiety disorder, please invite them to volunteer for the Living with Anxiety study at livingwithanxiety.org.au or email: lwa@qimrberghofer.edu.au
Professor Sarah Medland OAM, FASSA, FAHMS, PhD is the Lead Investigator of the Living with Anxiety study, and Coordinator of the Mental Health Research Program and Group Leader (Psychiatric Genetics) with QIMR Berghofer, Brisbane
Professor Ian Hickie AO MD, FRANZCP, FASSA, FAHM, FRSN is Co-Investigator of the Living with Anxiety study, and Professor of Psychiatry and Co-Director, Health and Policy at The University of Sydney Brain and Mind Centre, Sydney
Conflicts: Ian Hickie is the Co-Director, Health and Policy at the Brain and Mind Centre (BMC) University of Sydney. The BMC operates an early-intervention youth services at Camperdown under contract to headspace. He is the Chief Scientific Advisor to, and a 3.2% equity shareholder in, InnoWell Pty Ltd which aims to transform mental health services through the use of innovative technologies.
The statements or opinions expressed in this article reflect the views of the authors and do not necessarily represent the official policy of the AMA, the MJA or InSight+ unless so stated.
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