None listed
Conditions
Brief summary
Depression is the top leading cause of disability, yet existing treatments leave many people with a shortfall in recovery. In addition, medical and particularly cardiovascular comorbidity dramatically shortens the lives of people with depression, and there are no routine strategies to reduce this burden. Current evidence suggests a possible aetiological role for inflammation in the genesis and pathophysiology of depression and comorbid medical disorders especially cardiovascular disorder. Statins and metformin reduce inflammation and have established benefits for medical comorbidity. Both agents show antidepressant effects in preclinical models. Multiple epidemiology studies and preliminary clinical trial data suggests an antidepressant effect of both agents. Hearts and Minds is a 3-arm multicentre, randomised, double-blind, trial of atorvastatin (40 mg daily) and metformin (2000 mg daily) for the treatment of depression in people who remain symptomatic after a trial of established therapy. This will be a 16-week placebo-controlled trial with a 6 month follow up period.
Interventions
16 weeks of adjunctive Metformin 2000mg oral tablet daily or Atorvastatin 40mg oral tablet daily. Adherence to intervention will be monitored via counting of returned medication.
Sponsors
Deakin University
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 No maximum
Healthy volunteers
No
Inclusion criteria
1. A DSM-5 diagnosis of current major depressive disorder determined by the SCID-5-RV 2. Moderate to severe depression indexed by a MADRS score of = 20. the MADRS will be administered at baseline to confirm ongoing eligibility prior to dispensing of study IP/administration of medication; 3. Aged 18 years and above; 4. Have the capacity to consent to the study and to follow its instructions and procedures; 5. Participants will need to have been on stable pre-existing pharmacological or psychotherapy regimens for two weeks prior to study entry; 6. Be using effective contraception if female, sexually active and of childbearing age; 7. Be able to speak, read, write, and understand the English language, 8. Participants will be required to nominate a current treating physician, 9. Willing to consent to blood collection for safety monitoring.
Exclusion criteria
Exclusion criteria: 1. A diagnosis of bipolar disorder and/or another psychotic disorder and/or current substance use disorder, assessed using the SCID-5-RV; 2. Undergoing Electroconvulsive Therapy (ECT) or Transcranial Magnetic Stimulation (TMS) within one month of randomisation in the study; 3. Known or suspected clinically unstable systemic medical disorder, including heart disease especially congestive heart failure, cerebrovascular, liver or kidney disease including renal artery stenosis; 4. Participants currently taking atorvastatin or other statins such as simvastatin, lovastatin, pitavastatin, pravastatin, and rosuvastatin will be ineligible, although previous use of these (i.e., cessation at least two weeks prior to entrance in the study) will not preclude participation; 5. Participants who have received a clinical diagnosis of diabetes (‘pre-diabetes’ or ‘insulin resistance’ are not exclusionary) or any other clinical indication that requires the continuation of metformin will be excluded from participating in this study. However, individuals who do not have a clinical requirement for continued use of metformin and are willing to discontinue metformin two weeks prior to randomisation can be included; 6. Participants with severe renal impairment (CrCl<30ml/min) or liver function tests > 3 times upper limit of normal; 7. Current use of medications contraindicated with concurrent use of atorvastatin: CYPA4 inhibitors (e.g. Itraconazole, ketoconazole, erythromycin, clarithromycin, telithromycin), CYP3A4 inducers (e.g. rifampicin, phenytoin, efavirenz, carbamazepine), HIV protease inhibitors, Paxlovid therapy (for treating COVID) 8. Current use of medications contraindicated with concurrent use of metformin 9. Contraindications, intolerance or allergy to atorvastatin or any of the trial preparations; 10. Contraindications, intolerance or allergy to metformin or any of the trial preparations 11. Acute or chronic metabolic acidosis, including diabetic ketoacidosis, with or without coma. 12. People of Child-Bearing Potential (POCBP) who are: currently pregnant, are planning on becoming pregnant, or who are breastfeeding; 13. Current enrolment in another psychiatric intervention study; 14. Participants with current suicidal ideation with a specific plan, defined as a score of 5 or 6 on the MADRS item 10;
Outcome results
None listed