Omega-3 Fatty Acids in the Prevention of Interferon-Alpha-Induced Depression: Results From a Randomized, Controlled Trial

Biol Psychiatry. 2014 Oct 1;76(7):559-66. doi: 10.1016/j.biopsych.2014.01.008. Epub 2014 Jan 24.

Abstract

Background: Interferon (IFN)-α therapy for chronic hepatitis C virus infection is frequently associated with depression. The routine prophylaxis with antidepressants might expose patients to adverse effects, hence, the need for alternative preventive interventions. Omega-3 polyunsaturated fatty acids are safe and effective essential nutritional compounds used for the treatment of depression, putatively through an anti-inflammatory action. In addition, lower erythrocyte levels of omega-3 polyunsaturated fatty acids have been associated with an increased risk of IFN-induced depression.

Methods: We conducted a 2-week, double-blind, placebo-controlled trial comparing eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and placebo for the prevention of IFN-α-induced depression. A total of 162 patients consented to participate and were randomized to the study. All of the patients completed the 2-week trial; 152 participants were followed throughout the 24 weeks of IFN-α treatment and were included in the analysis.

Results: Compared with placebo, the incident rates of IFN-α-induced depression were significantly lower in EPA-treated but not in DHA-treated patients (10% and 28%, respectively, versus 30% for placebo, p = .037). Both EPA and DHA significantly delayed the onset of IFN-induced depression (week of onset: 12.0 and 11.7, respectively, versus 5.3 for placebo, p = .002). EPA and DHA were both well tolerated in this population. EPA treatment increased both EPA and DHA erythrocyte levels, but DHA only increased DHA erythrocyte levels.

Conclusions: EPA is effective in the prevention of depression in hepatitis C virus patients received IFN-α therapy. Our study confirms the notion that anti-inflammatory strategies are effective antidepressants in the context of depression associated with inflammation.

Trial registration: ClinicalTrials.gov NCT01620502.

Keywords: Chronic hepatitis C virus (HCV); clinical trial; inflammation; interferon-alpha (IFN-α); major depressive disorder (MDD); omega-3 polyunsaturated fatty acids (n-3 PUFAs).

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Depression / chemically induced*
  • Depression / prevention & control*
  • Docosahexaenoic Acids / therapeutic use*
  • Double-Blind Method
  • Eicosapentaenoic Acid / therapeutic use*
  • Female
  • Hepatitis C / drug therapy*
  • Humans
  • Interferon-alpha / adverse effects*
  • Male
  • Middle Aged

Substances

  • Interferon-alpha
  • Docosahexaenoic Acids
  • Eicosapentaenoic Acid

Associated data

  • ClinicalTrials.gov/NCT01620502