A double-blind, randomized controlled trial of ethyl-eicosapentaenoate for major depressive disorder

Abstract

Objective: To examine the efficacy and tolerability of ethyl-eicosapentaenoate (EPA-E) monotherapy for major depressive disorder (MDD).

Method: Fifty-seven adults with DSM-IV MDD were randomly assigned from January 2003 until June 2006 to receive 1 g/d of eicosapentaenoic acid (EPA) or placebo for 8 weeks in a double-blind, randomized, controlled pilot study. Response criteria were on the basis of the 17-item Hamilton Depression Rating Scale (HDRS-17). Subjects' plasma lipid profiles were examined by gas chromatography.

Results: Thirty-five subjects (63% female; mean +/- SD age = 45 +/- 13 years) were eligible for the intent-to-treat (ITT) analysis. In the ITT sample, mean +/- SD HDRS-17 scores decreased from 21.6 +/- 2.7 to 13.9 +/- 8.9 for the EPA group (n = 16) and from 20.5 +/- 3.6 to 17.5 +/- 7.5 for the placebo group (n = 19) (P = .123); the effect size for EPA was 0.55. ITT response rates were 38% (6/16) for EPA, and 21% (4/19) for placebo (P = .45). Among the 24 study completers, mean +/- SD HDRS-17 scores decreased from 21.3 +/- 3.0 to 11.1 +/- 8.1 for the EPA group and from 20.5 +/- 3.8 to 16.3 +/- 6.9 for the placebo group (P = .087); the effect size for EPA was 0.73. Completer response rates were 45% (5/11) for EPA, and 23% (3/13) for placebo (P = .39). Among EPA subjects, baseline n-6/n-3 ratio was associated with decrease in HDRS-17 score (r = -0.686, P = .030) and with treatment response (P = .032); change in n-6/n-3 ratio was associated with change in HDRS-17 score (r = .784, P = .032). Side effects, reported in 2 EPA subjects and 5 placebo subjects, were exclusively gastrointestinal, mild, and not associated with discontinuation.

Conclusions: EPA demonstrated an advantage over placebo that did not reach statistical significance, possibly due to the small sample and low completer rates, which were the major study limitations.

Trial registration: clinicaltrials.gov Identifier: NCT00096798.

Figure 1. Change in HAM-D-17 score over time for each treatment group (completers)

*EPA group had a significant decrease in HAM-D-17 score after 8 weeks of treatment (p=0.004)

Figure 2. Response and Remission Rates for Each Treatment Group (completers)

* Fisher's p=0.39 for EPA group vs Placebo (PBO) + Fisher's p=0.36 for EPA group vs Placebo (PBO)