Seventy-five individuals were assessed for eligibility and 45 met entry criteria and were enrolled. After the one week placebo run-in period, 42 subjects continued to meet entry criteria and were randomized to the two study arms. In the citalopram + omega-3 treatment group, of the 20 initial subjects, two subjects were terminated and excluded from analysis due to previously undisclosed exclusion criteria (alcohol abuse, bipolar disorder) and one subject was lost to follow up. Among the 22 subjects randomized to the citalopram + placebo treatment group, two subjects withdrew specifically because of lack of efficacy, while five were lost to follow-up. There was no statistical difference in the drop-out rates between the two treatment groups (p = 0.118). There was also no association of drop-out rates by severity of depression as measured by HAM-D scores or by any demographic measure.
Study participants were an average of 40.5 ± 10.2 years old with 15% experiencing a first episode of MDD and an average current episode length of 21.8 ± 24.3 months. The average HAM-D score at baseline was 25.3 ± 4.4. Baseline demographic, medical and depression history measures were similar between the two study groups. The only significant difference between the two study groups at baseline was a higher MADRS score in the placebo-treated group (27.5 ± 6.3) than the omega-3 treated group (24.2 ± 3.7) (t = −2.1,35df, p = 0.048).
There was no difference in the dosing regimen of citalopram between the two treatment arms. At study week 4, citalopram dosing was increased from the initial 20 mg/day to 40 mg/day in 11 of 18 subjects (61%) in the omega-3 treated group, and in 9 of 18 subjects (50%) in the placebo-treated group (
= 0.502). At study week 6, 14/18 (78%) in the omega-3 treated group and 10/17 (59%) in the placebo treated group were receiving citalopram (40 mg/day) (
= 0.227) .
In the intent-to-treat analysis, and after covarying for citalopram dose prescribed, there was significantly greater improvement over time in HAM-D scores among subjects in the omega-3 treated group than in the placebo-treated group (group x time interaction,
= 0.008) (). Significant differences were noted between the treatment groups at study week 4 (t
= 0.018) , week 6 (t
= 0.007) , and at study completion (t
= 0.006) . Furthermore, there was statistically significant improvement in the omega-3 treated group over the placebo treated group in terms of remission status (p = 0.018) (). There were trends for a group x time interaction for BDI scores (
= 0.171) and MADRS scores (after covarying for differences at baseline,
= 0.124). We observed no changes in plasma CRP or 24 hour urinary cortisol levels over the eight weeks of study (data not shown.)
HAM-D measures of depressive symptoms for subjects treated with citalopram + placebo or citalopram + omega-3 supplements over the 8 weeks of study, mean ± standard deviation (* p < 0.05, computed via regression modeling).
Categorical improvement rates across both treatment groups.
Based on detectable blood levels of citalopram, adherence to the treatment protocol was 89% in the omega-3 treatment group and 100% in the placebo-treated group. Analysis of only adherent subjects found no notable differences in these overall findings. The most frequently reported side effects were largely gastro-intestinal in nature such as nausea, diarrhea, indigestion, and constipation with 6/18 (33%) in the omega-3 group reporting such adverse events and 4/22 (18%) in the placebo-treated group. Less than 5% of subjects in either group reported other side effects such as headache, sedation, or sexual dysfunction. There were no significant adverse events observed.