Clinical trials of PUFAs in depression: State of the art.

Omega fatty acid treatment of depression is an unusual story in psychopharmacology in that the use and study of these compounds were advanced in cardiovascular disease before becoming of interest in psychiatry. Given the absence of an easily patentable derivative it is a tribute to the field that enough studies have accumulated for a reasonable review of omega-3 treatment of depression at this time. On the other hand, it is clearly not possible to compare the number of studies, variety of studies and the number of participants in each study with Federal Drug Administration style registration trials of patented antidepressant drugs. Most of the available studies of omega-3 in depression have been investigator initiated and use add-on design. This paper reviews 12 published and as yet unpublished clinical trials (all but one double-blind placebo-controlled) of polyunsaturated fatty acids in unipolar depression, bipolar disorder, and special populations with affective/depressive disorders. While overall results up to this point are encouraging, they are not unanimously positive. Outstanding issues that have not as yet been resolved include the dose of omega-3 necessary and the length of time required for significant response. Moreover, the complex issue of the relationship between two possible active ingredients, eicosapentaenoic acid and docosahexaenoic acid, remains unresolved.