Omega-3 Fatty Acids for Major Depressive Disorder With High Inflammation: A Personalized Approach

Inclusion Criteria

• Able to provide informed consent.
• Men or women aged 18-80 years.
• A primary psychiatric diagnosis of major depressive disorder (MDD), by Diagnostic and Statistical Manual-5th ed (DSM-5) using the Mini International Neuropsychiatric Interview (MINI v.7.0).
• A Screening and Baseline visit Inventory of Depressive Symptoms, Clinician rated (IDS-C30) total score ≥ 25.
• Currently overweight at screening, defined as BMI > 25 kg/m2.
• Screening visit high-sensitivity C-reactive protein concentration ≥ 3 mg/L.
• Willing to not significantly modify their diet from the time they sign consent through the end of study participation.

Exclusion Criteria

• Use of any psychotropic agents within 2 weeks of baseline or at any time during the study, with the exception of prescription hypnotics (eszopiclone, zaleplon, zolpidem, suvorexant, ramelteon), diphenhydramine, or a stable daily dose of a benzodiazepine.
• Breastfeeding or pregnant women, women intending to become pregnant within 6 months of the screening visit, or women of child bearing potential who are not using a medically accepted means of contraception (defined as oral contraceptive pill or implant, condom, diaphragm, intrauterine device (IUD), status-post tubal ligation, or partner with vasectomy)
• Patients who, in the investigator's judgement, pose a current, serious suicidal or homicidal risk.
• Serious or unstable medical illness that in the investigator's opinion could compromise response to treatment or interpretation of study results.
• History of seizure disorder, except for childhood febrile seizures.
• Meeting DSM-5 criteria at any point in their lifetime, for any of the following: Neurocognitive Disorder, Psychotic Disorder, Bipolar disorder, Anorexia Nervosa
• Meeting DSM-5 criteria in the 3 months prior to the screening visit for any Substance Use Disorder (except nicotine or caffeine).
• Meeting DSM-5 criteria at screening for current obsessive compulsive disorder or bulimia nervosa.
• Presence of psychotic features at any time during the current major depressive episode.
• Any conditions or medications (within 1 week of baseline or during the trial) that might confound the biomarker findings, including: Regular ingestion of NSAIDs or Cyclooxygenase-2 (COX-2) inhibitors, or any use of oral steroids, immunosuppressants, interferon, chemotherapy, or anticoagulants (Patients will be instructed not to take a nonsteroidal antiinflammatory drug (NSAID) or COX-2 inhibitor in the 24 hours prior to a biomarker assessment visit), Malignancy not in remission for at least 1 year, Active autoimmune disorder or inflammatory bowel disease, Insulin-dependent diabetes mellitus.
• History of allergy to PUFA supplements.
• Laboratory evidence of undiagnosed hypothyroidism or change in treatment for hypothyroidism in the 3 months prior to screening.
• Patients who have failed to respond during the course of their current major depressive episode to >4 adequate antidepressant trials, defined as six weeks or more of treatment with the FDA-defined minimally effective dose.
• Patients who have taken a supplement of at least 1 g/day of omega 3 fatty acids for at least 6 weeks during the current major depressive episode.
• Patients who have had electroconvulsive therapy (ECT) during the current depressive episode or within 6 months of the screening visit.
• Patients who have taken supplements with omega-3 fatty acids (see Appendix A for list of products) within sixty (60) days of the screening visit.
• Patients who, at baseline, are consuming a diet that contains more than 3g/day of omega-3 FA, or who consume more than 3 meals of fatty fish per week.
• Patients who have a history of a bleeding disorder.
• Patients who have participated in another clinical trial of an investigational medication within 1 month of the screening visit.
• Patients who are currently in psychotherapy that was initiated within 90 days prior to the study screening visit.