Omega-3 Fatty Acids May Help Mood
abstract & commentary
Synopsis: This double-blind, placebo-controlled study found that the addition of high-dose omega-3 fatty acids in the form of fish oil improved the clinical course of patients with unstable bipolar disorder.
Source: Stoll A, et al. Omega-3 fatty acids in bipolar disorder: A preliminary double-blind, placebo-controlled trial. Arch Gen Psychiatry 1999;56:407-412.
The need for additional therapeutic modali-ties for the treatment of bipolar disorder (manic-depression) is particularly compelling because current treatments, such as lithium and valproate, are not effective in all patients, have a relatively high side effect burden, and are teratogenic. Omega-3 fatty acids are naturally occurring lipids most commonly found in cold water fish. Omega-3 fatty acids appear to attenuate intracellular signal-transduction pathways in a manner similar to lithium and valproate, which were discovered serendipitously. Based on this mechanistic commonality, Stoll and colleagues designed a controlled pilot study to assess the efficacy of omega-3 fatty acids as a potential treatment. This was a four-month parallel-group, placebo-controlled, double-blind study in which outpatients with bipolar disorder were randomized to receive either omega-3 fatty acids or placebo, in addition to their ongoing usual treatment. Omega-3 fatty acids ethyl esters were administered in gelatin capsules that contained 440 mg of eicosapentaenoic (EPA) acid and 240 mg of docosahexanoic acid (DHA), or olive oil ethyl esters (the placebo). Each subject received 14 capsules per day, for a total daily dose of 9.6 grams of omega-3 fatty acids in the active group. The product was obtained from the Fish Oil Test Materials Program, which was a joint program of the National Institutes of Health and the National Marine Fisheries Service. Subjects with evaluable data, based on a priori criteria, consisted of 30 patients with the diagnosis of bipolar disorder (type I or type II) who had experienced a manic or hypomanic episode in the past year. The fact that all subjects had a fairly recent episode of mania or hypomania enriches the cohort because this subgroup is at a higher risk for relapse. The randomization produced a comparable distribution of men and women, concomitant medications, and baseline mood states in the omega-3 and placebo groups. A Kaplan-Meier survival analysis, where survival is defined as remaining well enough to stay in the study (i.e., not requiring a medication change to treat mania or depression), was used as the primary outcome measure. As per this analysis, the omega-3 group had a significantly longer period of remission than the placebo group (P = 0.002). In addition, for every other outcome measure, the omega-3 group performed better than the placebo group. In a subgroup of eight patients who were receiving no other concomitant medications, the omega-3 group also demonstrated a significantly better outcome than the control group. The omega-3 fatty acids were well tolerated. Mild gastrointestinal upset and a "fishy taste" were the most common side effects.
Comment by Lauren B. Marangell, MD
Although the current study suffers from several limitations, these data, if replicated, are of clinical and theoretical import. One important point is that these substances are substantially less toxic than other available treatments and are not teratogenic. However, the current data are too preliminary to warrant widespread use, or monotherapy treatment, except perhaps in patients with very mild illness, or extenuating circumstances. The fact that omega-3 fatty acids are natural substances is appealing to many patients, which may increase acceptance of treatment. As with other natural substances, physicians must educate patients to avoid self-medication. At this time, it is not clear what the appropriate dose or preparation is for optimal treatment. Commercial fish oil preparations are a combination of EPA and DHA and vegetable-derived sources of DHA are available. Although the current study was not designed to assess acute antidepressant effects, the data suggest a trend toward improved depression ratings warranting further evaluation of these compounds for the treatment of depression.
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