The Effect of Fish Oil in Major Depressive Disorder

The Effect of Fish Oil in Major Depressive Disorder: a Double-blind Placebo-controlled Monotherapy Trail to Demonstrate the Therapeutic Effects of Depression

The first part is a double-blind placebo-controlled trial to identify the effects of omega-3 polyunsaturated fatty acids (PUFAs) monotherapy in depression. The second part is a double-blind trial to identify the effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on different symptom clusters in patients with depression.

With the dissatisfaction of monoamine-based pharmacotherapy and the high comorbidity of physical illness in depression, the serotonin hypothesis seems to fail in approaching the etiology of depression. Based upon the evidence from epidemiological data, case-control studies of PUFAs levels in human tissues, and antidepressant effect in clinical trials, phospholipid PUFAs is enlightening a promising path to discover the unsolved of depression. The PUFAs are classified into n-3 (or omega-3) and n-6 (or omega-6) groups. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), the major bioactive components of n-3 PUFAs, are not synthesized in humans and can only be obtained directly from the diet, particularly by consuming fish. The deficit of n-3 PUFAs has been reported to be associated with neurological, cardiovascular, cerebrovascular, autoimmune, and metabolic diseases. Recent studies revealed that the deficit of n-3 PUFAs is also associated with depression. More specifically, societies that consume a small amount of omega-3 PUFAs appear to have a higher prevalence of major depressive disorder. In addition, depressive patients had showed a lower level of omega-3 PUFAs; and the antidepressant effect of PUFAs had been reported in a number of clinical trials. Theoretically, DHA deficit is associated with dysfunctions of neuronal membrane stability and transmission of serotonin, norepinephrine and dopamine, which might connect to etiology of depression. On the other hand, EPA is important in balancing the immune function by reducing membrane arachidonic acid (AA, an n-6 PUFA) and prostaglandin E2 (PGE2) synthesis. Interestingly, animals fed with high AA diet or treated with PGE2 present sickness behaviors of anorexia, low activity, change in sleep pattern and attention, which are similar to somatic symptoms of depression in human. There are little data at this stage to reveal whether the oral administration of omega-3 fatty acids monotherapy would lead to an effective mood stabilization in major depressive disorder. In addition, the active component of antidepressant effect in n-3 PUFAs is still unknown. In this project, the first part is a double-blind placebo-controlled trial to identify the effects of omega-3 PUFAs monotherapy in depression. The second part is a double-blind trial to identify the effects of EPA and DHA on different symptom clusters in patients with depression.

Inclusion Criteria: DSM-IV criteria for major depressive disorder. Age being age 18-65. Capacity and willingness to give written informed consent. Exclusion Criteria: Any major medical illnesses. A recent or past history of any Axis-I diagnoses besides major depressive disorder, including psychotic disorders; cognitively impaired mental disorders; impulse control disorders; substance use disorder or substance abuse (last 6 months prior to the studies); primary anxiety disorders, including post-traumatic stress disorder and panic disorder; and bipolar disorders; or Axis-II diagnoses, i.e. borderline and antisocial personality disorder.

Appleton KM, Voyias PD, Sallis HM, Dawson S, Ness AR, Churchill R, Perry R. Omega-3 fatty acids for depression in adults. Cochrane Database Syst Rev. 2021 Nov 24;11(11):CD004692. doi: 10.1002/14651858.CD004692.pub5.