Food and Behaviour Research

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Effects of eicosapentaenoic acid and fluoxetine on plasma cortisol, serum interleukin-1beta and interleukin-6 concentrations in patients with major depressive disorder.

Jazayeri S, Keshavarz SA, Tehrani-Doost M, Djalali M, Hosseini M, Amini H, Chamari M, Djazayery A. (2010) Psychiatry Res. 178(1) 112-5. Epub 2010 May 13. 

Web URL: View this and related abstracts via PubMed here


Treatment studies have suggested that omega-3 fatty acids (omega-3 FAs) as monotherapy or adjunctive treatment have therapeutic effects in depression.

The authors recently reported a study in which fluoxetine and eicosapentaenoic acid (EPA), which is an omega-3 fatty acid, appeared to be equally effective in controlling depressive symptoms and their combination was superior to either of them alone. Regulation of hypothalamus-pituitary-adrenal (HPA) axis activity and reduction of inflammatory cytokines are among several biological mechanisms which potentially explain the impact of omega-3 FAs on depression.

In the present study, plasma cortisol and serum interleukin-1beta (IL-1 beta) and interleukin-6 (Il-6) were measured in patients with a diagnosis of major depressive disorder (MDD) participating in aforementioned trial to determine the effects of 8 weeks of treatment of depression with 1000 mg EPA alone or in combination with 20 mg fluoxetine on HPA axis activity and inflammatory cytokine production and compare the changes in these variables with those of treating with 20 mg fluoxetine alone. Forty-two patients were included in analysis.

Two-way repeated measures analysis of variance (ANOVA) showed that plasma cortisol decreased significantly after 8 weeks of intervention without significant difference among the groups. There was no interaction between group and response to treatment over time in the cortisol response based on three-way ANOVA. Serum concentrations of IL-1beta and IL-6 did not change significantly after intervention.

In conclusion, EPA alone or in combination with fluoxetine, as well as fluoxetine alone decreased serum cortisol after 8 weeks of treatment in patients with major depression disorder (MDD) without any significant effect of response to treatment. Serum IL-1beta and IL-6 did not change significantly after intervention. These findings suggest that EPA may exert its therapeutic effects through reduction of cortisol.


This study involved patients with clinical depression (major depressive disorder), who took part in a previously reported treatment trial involving supplementation for 8 weeks with either EPA alone, fluoxetine (Prozac) alone, or both.

Results showed that EPA alone was as effective as fluoxetine alone in reducing depressive sysmptoms, but that the combination of the two was superior to either treatment alone.  For details, see:

In the current study, levels of both plasma cortisol (a biochemical marker of stress and increased HPA axis activity) and inflammatory cytokines were examined as possible mechanisms underlying the observed improvements in depressive symptoms.

No changes were seen in levels of inflammatory cytokines over the 8-week period.  However, plasma cortisol levels were reduced in all treatment groups, suggesting that the antidepressant effects of both EPA and fluoxetine may reflect a lowering of HPA axis activity.

For more information on this subject, please see the following lists of articles, which are regularly updated.