Context studies of depressed psychiatric patients have shown that antidepressantefficacy can be increased by augmentation with omega-3 fatty acids. Our objective was to determine whether omega-3 improves the response to sertraline in patients with major depression and coronary heart disease (CHD). Therefore between May 2005 and December 2008, 122 patients in St Louis, Missouri, with major depression and CHD participated in a  randomized in a controlled trial.

The trial was limited to 10 weeks, which may not have been long enough to observe an effect. However, there is no indication that longer treatment would have favored the omega-3 group. Although both groups showed improvement, the between-group difference in weekly BDI-II scores remained nearly identical throughout the trial. Furthermore, earlier positive studies found effects within 10 weeks.

We proposed to enroll 175 patients and expected to randomize 150 after the 2-week run-in phase during which patients received 25 mg/d of sertraline plus placebo capsules. We actually enrolled 178 patients, but 58 were excluded or dropped out before randomization, instead of the expected. In

most cases, this was because of improvement in depression prior to randomization, which placed the patient below the eligibility threshold; a decision by the patient to avoid possible randomization to a placebo and to seek omega-3 and antidepressants elsewhere; or new or previously unidentified medical or psychiatric exclusions. Although the enrolled sample was smaller than planned, it was large enough to detect the expected 4-point differences on the BDI-II and HAM-D. Furthermore, 670 patients would have been required to detect an effect for the observed 1.4-point difference on the BDI-II, and this difference favored the placebo group. Although some trials of omega-3 for depression have been strongly positive, others, including the present study, have failed to demonstrate a benefit, either alone or combined with conventional antidepressants. These contradictory findings mirror those of studies that have examined the efficacy of omega-3 supplements in reducing cardiac morbidity and mortality.38,39 Some have found that omega-3 supplements greatly reduce the incidence of sudden cardiac death.Others have failed to find a benefit, and still others have reported that omega-3 supplements increase the risk of cardiac death. These conflicting results have led to speculation about the clinical characteristics of cardiac patient subsets who may either benefit or be harmed by omega-3 supplements.

Efforts should be made to identify the characteristics of depressed patients who may benefit from omega-3 depression monotherapy or augmentation of standard antidepressants. Confirmatory

prospective clinical trials should then be undertaken in these subgroups. To this end, exploratory analyses are currently being conducted to determine whether any subgroups in this study benefited from omega-3.

In conclusion, this randomized, double-blind, placebo-controlled trial found no evidence that omega-3 augmentation of sertraline is superior to sertraline plus placebo capsules for the

 reatment of depression in patients with major depression and established CHD. Whether higher doses of EPA, DHA, or sertraline, a longer duration of treatment, or the use of omega-3 as monotherapy can improve depression in patients with stable heart disease remains

to be determined.

summarised by permission from the original article JAMA. 2009,302(15):1651-1657 (doi:10.1001/jama.2009.1487)