Omega-3 fatty acids in the prevention of interferon- Alpha-induced depression: Results from a randomized, controlled trial

Kuan Pin Su, Hsueh Chou Lai, Hui Ting Yang, Wen Pang Su, Cheng Yuan Peng, Jane Pei Chen Chang, Hui Chih Chang, Carmine M. Pariante

Research output: Contribution to journalArticlepeer-review

145 Citations (Scopus)


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 DHAtreated patients (10% and 28%, respectively, versus 30% for placebo, p = .037). Both EPA and DHA significantly delayed the onset of IFNinduced 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.

Original languageEnglish
Pages (from-to)559-566
Number of pages8
JournalBiological Psychiatry
Issue number7
Publication statusPublished - Jan 1 2014
Externally publishedYes


  • Chronic hepatitis C virus (HCV)
  • Clinical trial
  • Inflammation
  • Interferonalpha (IFA-α)
  • Major depressive disorder (MDD)
  • Omega-3 polyunsaturated fatty acids (N-3 PUFAs)

ASJC Scopus subject areas

  • Biological Psychiatry


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