Reply to commentary by Calabrese et al 1999 on fish oils in bipolar disorder

We appreciate Dr Calabrese's commentary on our study of omega-3 fatty acids as a new treatment of bipolar disorder. He correctly points out both the exciting aspects of omega-3 fatty acids as a therapy for patients with bipolar disorder, as well as the methodological shortcomings of our preliminary trial.

Dr Calabrese's constructive criticisms of the study methodology are reasonable and are issues that future studies should address. When evaluating the methods for our current study, it is important to keep in mind that this was a preliminary study designed to demonstrate the prophylactic efficacy of omega-3 fatty acids as mood stabilizers.

This double-blind, placebo-controlled clinical trial of omega-3 fatty acids in patients with bipolar disorder was important not only in demonstrating the efficacy of these essential lipids in patients with bipolar illness, but also in several other ways.

• First, the decision to study omega-3 fatty acids as putative mood stabilizers was based on a rational search of the medical literature regarding the shared biochemical mechanisms of the currently used mood stabilizers.
• Second, omega-3 fatty acids are a class of essential nutrients that seem to be deficient in "western" diets. Thus, this study may represent the first demonstration of an effective nutritional therapy for bipolar disorder.
• Another remarkable feature was the unusually high patient interest and acceptance of omega-3 fatty acids as mood stabilizers. This interest was based mainly on the recognition that omega-3 fatty acids are endogenous, "natural" compounds with few side-effects and little, if any, toxic effects.

Omega-3 Fatty acids may prove to be efficacious, well-tolerated, inexpensive, and desirable mood stabilizing compounds. Whether one or both of the omega-3 fatty acids in fish oil are biologically active in bipolar disorder remains an open question. Well-controlled studies designed to replicate and extend the results of the present study are needed.

• One final point regarding our study in particular, and for future omega-3 fatty acid research in general, is that this clinical trial was conducted with very limited research funding. For compounds that are difficult to patent, such as omega-3 fatty acids, traditional research support from the pharmaceutical industry is not readily available. Thus, federal funding or unusually large private foundation support may be the only means to perform a well-designed, large-scale definitive study of the 3 fatty acids and other promising "nutriceuticals" for the treatment of psychiatric disorders.