Specialized Pro-resolving Lipid Mediators and Treatment Resistant Depression

Inclusion Criteria: Age: 18 and above Patients with MDD who have not responded to at least 2 and no more than 5 antidepressant trials during the current episode and have been on a current stable antidepressant regiment for at least 4 weeks. The diagnosis of MDD will be confirmed using the MINI and the historical failure to respond to antidepressant therapy will be documented using the Antidepressant Treatment Response Questionnaire (ATRQ), with failure to respond defined as less than 50% improvement by subject history. hs-CRP ≥ 3 mg/L and ≤ 10 mg/L BMI >25 kg/m2 17-item Hamilton Depression Rating Scale (HAM-D) score ≥15, and <25% decrease in score between screen and baseline Able to clearly understand English Exclusion Criteria: Diagnostic Exclusions: Meeting lifetime DSM-5 criteria for: a neurocognitive disorder, psychotic disorder, bipolar disorder, or anorexia nervosa in the 3 months prior to the screening; any substance use disorder (except for nicotine or caffeine use disorder); obsessive compulsive disorder or bulimia nervosa. Patients who, in the investigator's judgment, pose a current, serious suicidal or homicidal risk Presence of a serious or unstable medical illness, including insulin-dependent diabetes mellitus or bleeding disorder which, in the investigator's opinion, could compromise response to treatment, participant safety, or interpretation of study results Currently breastfeeding or pregnant women Currently participating in another clinical trial Treatment and Concomitant Medication Exclusions: Failure to respond during the course of the current major depressive episode to >5 adequate antidepressant trials Current use of antipsychotic medications or lithium Having received ketamine therapy within 90 days of the screening visit Patients who have initiated psychotherapy ≤ 90 days prior to screening.Having received electroconvulsive therapy during the current depressive episode or within 6 months of the screening visit Concomitant use of any psychotropic agents within 2 weeks of the baseline visit, except for the ongoing antidepressant, prescription hypnotics, diphenhydramine, or a stable daily dose of a benzodiazepine. Concomitant medications that might confound the biomarker findings within 1 week of the baseline visit and during the trial, including: regular (i.e. more than three times per week) ingestion of non-steroidal anti-inflammatory drugs (NSAIDs) or cyclooxygenase (COX)-2 inhibitors; any use of oral steroids, immunosuppressants, interferon, chemotherapy, or anticoagulants. Omega-3 Exclusions: A history of severe sensitivity to soy products, fish products, or PUFA supplements Patients who had taken supplements enriched with n-3 fatty acids within 60 days of the screening visit or who, at baseline, were consuming a diet containing > 3 g/day of n-3 fatty acids, or who consume > 2 meals of fatty fish per week. Having taken a supplement of ≥1 g/day of n-3 fatty acids for ≥6 weeks during the current major depressive episode Patients who have had either a poor response or intolerable side effects from n-3s in the past. Patients with the following conditions: Crohn's disease, Irritable Bowel Syndrome-diarrhea type, history of gastric bypass surgery, history of cholecystectomy, recent/current history of bulimia with purging, use of prokinetic medications that affect GI transit time, and small intestinal bacterial overgrowth (SIBO)