None listed
Conditions
Brief summary
Depression is a common form of mental distress that affects 1 in 7 Australians in their lifetime. People who are depressed not only feel depressed and sad, but often find they sleep poorly, experience a change in appetite, have low energy, poor concentration and have lowered self-esteem. Sometimes, they might think of harming themselves. Often, they find it hard to enjoy life or be productive. Recovery from depression is possible and treatment for depression includes psychotherapy (talking therapy), cognitive behavioural therapy and medication. In fact, almost 10% of Australians use antidepressants each year. Finding the right medication and the right dose can be challenging, often requiring several trial-and-error attempts. Approximately two thirds of people do not get better with the first medication they’re prescribed and one third of people do not recover even after four different medications are tried. Pharmacogenomics is a new, simple genetic test which can determine the way a person’s body will respond to medication. The ALIGNED Study (AustraLIan trial of GeNotype-guided pharmacothErapy for Depression) is looking at how pharmacogenomics can help to find the right antidepressant medication for people with depression. This may improve the likelihood of recovery from depression.
Interventions
Materials used: a Treatment Guide will be prepared by the Treatment Guide Writing Group; the Treatment Guide will list recommended antidepressant medication(s) that are TGA approved/PBS-listed, chosen from current practice guidelines (Australian and New Zealand College of Psychiatrists’ Clinical Practice Guidelines for Major Depression, 2018 and the latest edition of Therapeutic Guidelines: Psychotropic (Version 8)) for participants based on their pharmacogenomic test results. Participants in th
Materials used: a Treatment Guide will be prepared by the Treatment Guide Writing Group; the Treatment Guide will list recommended antidepressant medication(s) that are TGA approved/PBS-listed, chosen from current practice guidelines (Australian and New Zealand College of Psychiatrists’ Clinical Practice Guidelines for Major Depression, 2018 and the latest edition of Therapeutic Guidelines: Psychotropic (Version 8)) for participants based on their pharmacogenomic test results. Participants in the intervention group will be given an individualised Treatment Guide based on their pharmacogenomic results. The Treatment Guide may recommend a lower starting dose but with a therapeutic dose that falls within the TGA-recommended dosing range. It is unlikely that the individualised Treatment Guide will recommend a maintenance dose that deviates from the TGA-recommended dosing range, and under no circumstance will the Treatment Guide recommend a dose higher than the maximum TGA-recommended dose. Participants in the control group will be given a standard treatment plan that adheres to TGA-recommended doses based on current ANZ guidelines. Procedure and activities: pharmacogenomic testing will be used to identify the most appropriate antidepressant medication(s) for participants. Participants will be provided with a kit to collect a buccal swab sample at home, which will be shipped to the pharmacogenomic testing laboratory by courier. A single pharmacogenomic test will take place from a single sample collected at baseline. Pharmacogenomic testing will occur 10-14 days prior to participants commencing treatment per their individualised Treatment Guide. The results of the pharmacogenomic testing will be provided to participants’ treating clinician. Participants will be encouraged to discuss their results with their treating clinician. A Treatment Guide Writing Group will prepare individual Treatment Guides for participants based on their pharmacogenomic test results. The Treatment Guide Writing Group will comprise registered psychiatrists, a registered clinical geneticist, a general practitioner, psychiatry and clinical genetics registrars. Intervention delivery: the Treatment Guide will be provided to the participant’s treating clinician e.g. GP, who will prescribe antidepressant therapy according to the recommendation(s) in the Treatment Guide. Mode of intervention delivery: prescription of antidepressant therapy will be done by the participant’s treating clinician during a standard-of-care clinic visit. Frequency of intervention: the intervention will be delivered once, within 7 days of day 0, following which, participants will be monitored by their treating clinician and depending on their response, the treating clinician has the discretion of deciding whether prescription changes are needed. If prescription changes are needed, the treating clinician is advised to follow the recommendations made in the Treatment Guide. Unblinding will occur at the week 12 time point (after week 12 assessments have been completed). The results of the pharmacogenomic testing will be provided to participants’ treating clinician. Participants will be encouraged to discuss their results with their treating clinician. The overall duration of the study is 12 weeks. Participants will also be followed by the study team at regular time points over 12 weeks. Location where intervention occurs: the intervention occurs at the participant’s treating clinician’s clinic as part of routine standard-of-care visit. Assessment of adherence to intervention: the antidepressant(s) prescribed to participants by their treating clinician (determined by participant self-report, review of PBS data) will be compared to those recommended by the Treatment Guide to assess clinician adherence to the intervention. Participant adherence to intervention will be assessed by validated adherence scales at regular time points.
Sponsors
The George Institute for Global Health
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
All
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. Aged between 18 and 80 years (inclusive) 2. Sufficiently fluent in English 3. Diagnosed with Major Depressive Disorder, either first-episode or relapsed, on the Mini-International Neuropsychiatric Interview Diagnostic and Statistical Manual of Mental Disorders (DSM)-5 criteria 4. Person in whom antidepressants are indicated based on the current ANZ guideline but are yet to be initiated during current episode OR planning to switch antidepressant treatment in current episode 5. Willing and able to provide informed consent
Exclusion criteria
1.. Intellectual impairment or dementia limiting capacity to provide informed consent 2. Current history of hepatic or renal failure confounding drug metabolism 3. Contraindication, including hypersensitivity (e.g. anaphylaxis), to SSRI, SNRI, mirtazapine and moclobemide. 4. Pregnant or breast feeding
Outcome results
None listed