Bottomline: Depressed patients had significantly elevated arachidonic acid and inflammation biomarkers.  Notably, depressed patients who were unresponsive to medication, had a markedly low EPA to arachidonic acid ratio in their blood. J Psychiatric Res (2008), doi:10.1016/j.jpsychires.2008.06.003.

Background: While there are several anti-depressant medications used to treat major depressive disorder, a significant amount of patients will not respond to medication (non-responders). Previous studies show that inflammation may be a contributing factor to medication failure. 

Summary:  Researchers evaluated plasma levels of fatty acids and inflammation biomarkers in three groups of people:  20 depressed patients who did not respond to medication; 14 depressed patients who responded to medication; and 24 healthy controls.  All of the patients met the diagnostic criteria for major depressive disorder.   The antidepressant medications used were selective serotonin reuptake inhibitors (SSRIs).

Both groups of depressed patients had significantly higher levels of arachidonic acid and pro-inflammatory cytokine interleukin-6, compared to healthy controls. Furthermore, patients who did not respond to medication had a lower EPA to arachidonic acid ratio, which suggests a skewing of the balance between omega-3 to omega-6 fatty acids. The data are indicative of a pro-inflammatory state in major depression with activation of the arachidonic acid cascade.  Notably, the inflammation state persists even when mood is returned to normal from treatment with anti-depressant medication.

Study Quote: “...major depression is associated with a high omega-6 to omega-3 ratio and elevation in the cytokine interleukin-6. Depression significantly increases the risk of cardiovascular disease and the present data may be relevant in explaining the link.”

Comment:  A  random-double-blind control study on 60 patients (Jazayeri et al) showed that EPA alone was comparable to using the antidepressant, fluoxetine (prozac) for treating depression.  (Fluoxetine is a selective serotonin reuptake inhibitor, SSRI.)

Furthermore, there was a superior impact when both EPA and fluoxetine were used together, reflected by improvement in symptoms using the Hamilton Depression Rating Scale.  While the researchers did not measure blood levels, they theorized that the synergistic effect was from EPA’s ability to lower pro-inflammatory cytokines.  Notably, cytokines can also lower serotonin production.

The American Psychiatric Association recommends that patients with mood disorders take at least one gram of omega-3 fatty acids in the form of  DHA + EPA, the type found in fish (Freeman et al).

Links to Sources:
Dinan T, Siggins L, Scully P, O'Brien S, Ross P, Stanton C.
Investigating the inflammatory phenotype of major depression: Focus on cytokines and polyunsaturated fatty acids. Journal of Psychiatric Research (2008), doi:10.1016/j.jpsychires.2008.06.003.

Freeman MP, Hibbeln JR, Wisner KL, Davis JM, Mischoulon D, Peet M, Keck PE Jr, Marangell LB, Richardson AJ, Lake J, Stoll AL.
Omega-3 fatty acids: evidence basis for treatment and future research in
psychiatry. J Clin Psychiatry. 2006 Dec;67(12):1954-67.

Jazayeri, S, Tehrani-Doost M, Keshavarz SA., Hosseini M, Abolghassem, Amini, Homayoun, Jalali, Mahmoud & Peet, Malcolm (2008). Comparison of therapeutic effects of omega-3 fatty acid eicosapentaenoic acid and fluoxetine, separately and in combination, in major depressive disorder. Australian and New Zealand Journal of Psychiatry, 2008 42 (3), 192-198. Retrieved December 15, 2008, from www.informaworld.com/10.1080/00048670701827275. style="background: gray none repeat scroll 0% 0%; overflow: auto ! important; position: absolute; left: 0px; top: 278px; width: 5px; height: 100%; z-index: 10000000; -moz-background-clip: -moz-initial; -moz-background-origin: -moz-initial; -moz-background-inline-policy: -moz-initial; opacity: 0; font-weight: bold ! important; font-size: medium ! important; font-style: normal ! important;" id="hwContLayer">