None listed
Conditions
Brief summary
The aim of this research is to evaluate the role of dysbiosis and probiotics and orotic acid as a treatment for depressive illness that does not respond to standard medication treatment. The mechanisms of probiotics in the treatment of dysbiosis and systemic inflammation and orotic acid as a treatment for resistant depression will also be evaluated. Significance: Developing effective and safe treatments for resistant depression is essential as this group presents a significant burden of care to the health system and generally have poorer vocational and quality of life outcomes and are at increased risk of morbidity and mortality. Dysbiosis and ensuing systemic inflammation has been strongly implicated in depression that has a poor treatment response. Orotic acid rapidly metabolises into uridine which has proven antidepressant effects through mechanisms different to antidepressant medication. Orotic acid demonstrated efficacy in our previous pilot work. The expected outcome of this study is to provide preliminary efficacy and safety data, and elucidate the mechanism of probiotics and orotoic acid as an adjuvant therapy with one class of standard medication.
Interventions
The project intervention will consist of n=250 using a randomised parallel treatment trial to test the efficacy of the oral administration of specific strain probiotics and orotic acid administered in conjunction with selective serotonin uptake inhibiters (SSRI) for treatment resistant depression.
The project time line will consist of rolling recruitment and block allocation to conditions. All participants will be inducted into a 2 week precondition where they will receive 2x placebo capsules
The project intervention will consist of n=250 using a randomised parallel treatment trial to test the efficacy of the oral administration of specific strain probiotics and orotic acid administered in conjunction with selective serotonin uptake inhibiters (SSRI) for treatment resistant depression. The project time line will consist of rolling recruitment and block allocation to conditions. All participants will be inducted into a 2 week precondition where they will receive 2x placebo capsules daily to identify placebo responders. Placebo capsules (microcellulose) will be identical the probiotic and the Mg orotate tablets used in the experimental phase of the study. All participants are then allocated to a 2 week probiotic run in period and receive 2 probiotic capsules daily followed by random allocation to either 1. probiotic + orotic acid (Magnesium form: Mg orotate) and 2., probiotic and placebo groups for 8 weeks with a 4 week follow up assessment. Total study duration is 16 weeks for participants with repeated recruitments over a minimum of 24 months. . Probiotic: A daily dose of 2 probiotic capsules taken orally, 1 x morning and 1 x evening with a meal. Each capsule contains 50 billion colony-forming units (CFU) of live organisms (Lactobacillus acidophilus +Lactobacillus casei +Lactobacillus rhamnosus JB-1.) Orotic acid: A daily oral dose of 4 x Mg orotate taken 2 x morning and 2 x evening with a meal, yielding 1600mg of orotate. Each participant will be taking SSRI medication prescribed by their own medical practitioner as part of the selection criteria, and they will continue taking their medication throughout the study. Supplement and SSRI compliance will be monitored by fortnightly contact with each participant by a research assistant and a dosage log book that must be completed by participants on a daily basis throughout the study.
Sponsors
Professor Luis Vitetta
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Be depressed,, with depression as primary diagnosis, while taking SSRI antidepressant medication as prescribed by a doctor 2. Currently be under the management of a medical practitioner e.g. family doctor or a psychiatrist 3. Have a history of depression that has not responded well to medication, with at least 2 previous episodes 4. Be over 18 years of age and have the capacity to provide informed consent 5. Have the willingness and ability to comply with assessment protocols of the study
Exclusion criteria
1. Resistant depression not being the primary diagnosis 2. Current substance misuse 3. Other psychiatric disorder as primary diagnosis 4. Active suicidality 5. Not able to understand or conform to study requirements 6. Subject to a mental health or guardianship order
Outcome results
None listed