To the Editor: We read with interest the article by Gordon Parker, M.D., Ph.D., D.Sc., F.R.A.N.Z.C.P., et al. on omega-3 fatty acids and mood disorders (1). Patients with mood disorder frequently use omega-3 fatty acids; therefore, it is important to review the available evidence. Although the epidemiological studies are very interesting from a theoretical point of view, the controlled clinical trials are crucial in clinical decision making.
It is from the clinical perspective that we want to make two remarks. First, we would like to point to two double-blind, placebo-controlled trials of the Stanley Foundation Bipolar Network (2, 3). In both studies, 6 grams of eicosapentaenoic acid were added to ongoing treatment. In the first study, 59 patients with an acute bipolar depression were treated with eicosapentaenoic acid or placebo. In the second study, 62 patients with a rapid cycling bipolar depression were treated with eicosapentaenoic acid or placebo. Both studies failed to show significant differences between eicosapentaenoic acid and placebo. Although these studies are only available as abstracts, they underscore that the efficacy of eicosapentaenoic acid in bipolar depression is not yet proven.
Second, the authors suggest several topics for further research. We would like to extend their elaborate list with one topic: possible side effects. Besides gastrointestinal complaints, which are common (4, 5), two other possible side effects should be taken into account. Omega-3 fatty acids influence glucose-metabolism, and this might lead to lower glucose blood levels. Additional controls in patients with diabetes mellitus type II are also indicated (4, 5). Furthermore, there is the theoretical possibility that omega-3 fatty acids may cause prolonged bleeding time. This may be a risk in patients using anticoagulants (4, 5). The use of selective serotonin reuptake inhibitors has also been found to increase the risk of gastrointestinal bleeding, especially when combined with the use of a nonsteroidal anti-inflammatory drug or aspirin (6), a combination that is frequently used by depressed patients. The effect of adding omega-3 fatty acids to the risk of gastrointestinal bleeding is unknown. Psychiatrists should be aware of the possibility of an increased risk.
1.Parker G, Gibson NA, Brotchie H, Heruc G, Rees AM, Hadzi-Pavlovic D: Omega-3 fatty acids and mood disorders. Am J Psychiatry 2006; 163:969–978
2.Keck PE Jr, McElroy SL, Freeman MP, Altshuler LL, Frye MA, Kupka R, Nolen W, Grunze H, Walden J, Denicoff KD, Leverich GS, Post RM: Randomized, placebo-controlled trial of eicosapentanoic acid in bipolar depression. Bipol Disord 2003; 1(supp):S58 (abstract)
3.Keck PE Jr, McElroy SL, Freeman, MP, Altshuler LL, Frye MA, Kupka R, Nolen W, Grunze H, Walden J, Denicoff KD, Leverich GS, Post RM: Randomized, placebo-controlled trial of eicosapentanoic acid in rapid cycling bipolar disorder. Bipol Disord 2003; 1(suppl):S58 (abstract)
4.Peet M, Stokes C: Omega-3 fatty acids in the treatment of psychiatric disorders. Drugs 2005; 65:1051–1059
5.Lake J: Omega-3 fatty acids: theory, clinical trials and safety issues. Psychiatric Times 2002 (www.psychiatrictimes.com/p021028.html)
6.Weinrieb RM, Auriacombe M, Lynch KG, Lewis JD: Selective serotonin re-uptake inhibitors and the risk of bleeding. Expert Opin Drug Saf 2005; 4:337–344