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Omega-3 Fatty Acids

The most recent study here is the 2006 report by Frangou and colleagues. This appeared in the British Journal of Psychiatry, a well-respected journal. The study design was good. The sample is somewhat small, which may explain why they did not see an EPA-placebo difference unless they lumped both EPA groups together. But when lumped, there appears to be a clear effect. The effect is not large, however. Note also that their patients were also taking mood stabilizers, so this is fish oil as an add-on, not by itself as in the original study by Stoll that started this whole thing. Nevertheless, it suggests that a manageable dose of EPA might be sufficient (as opposed to larger 4-gram dose used in the Stanley Bipolar Foundation study reported by Post and colleagues, which was not effective). Interestingly, in this 2006 study, the response appears to show up by the 4th week of treatment (they didn't look sooner, trying to minimize the placebo effect of their attentions).

A patient whose long-term course is reported in Bipolar Network News demonstrated a stunning improvement which lasted over 1 year on omega-3's. Look at her life-chart picture on page 7 ( v.8, Issue 2, scroll to page 7) for the dramatic change in course, but notice how it took about a year to really take hold (or so we might guess, from this report, although the author points out that there could have been other variables to account for this change also). Notice also that the change was to stop depressive episodes, in this woman who had not had a manic phase in several years by that time on the medications which were continued as the omega-3's were added.

Finally, notice that the dose was 6 grams. In the accompanying article, which you can read via the link to that issue, some data are cited suggesting that a 6 gram dose of E-EPA may be too high and that a 1-4 gram dose may be preferable. However, if you want to hear a real fan letter for omega-3's, from a fellow who's taking more than 4 grams a day, read this testimonial. A local colleague takes just 2 grams of fish oil a day (500 mg of omega-3's total). She is certain it helped dramatically with PMS and mild mood swings (family history of bipolar disorder). She found 1 gram pills for $8.00/300 at Costco, so her cost is about $1.60 per month.

Update 2006: Now six years after the Stoll study I'm still talking about fish oil with my patients but still not very convinced it has great value as a mood stabilizer. However, as an add-on tool for depression, I think that's where it may indeed be useful. I've probably not been using large enough doses. The dose in the new Frangou study, 2006, is the equivalent in EPA of seven pills of the type I've been recommending -- because it's the cheapest, with no greater risk -- where I've generally had people taking 4 pills per day. I'll definitely be trying a higher dose when I talk with patients now, and looking for a cheap route to 1 gram of EPA (if you find one on the internet that will cost 20-30 cents per day and require less than 7 pills, write me and say where!).

[Update 8/2005: I now have one patient who had such severe symptoms she was labeled "borderline", for whom complete symptom control required three mood stabilizers (although this was during an awful divorce). She later tapered off all three of these medications, but her symptoms returned (milder, years after the divorce, but clearly causing problems in her life). She had to go back on a two-mood-stabilizer regimen to control these symptoms. I just saw her yesterday: she is now on fish oil alone, at 0.75 grams of omega-3, and doing pretty well, far better than she did on no medications. She still has some symptoms, however, so we are trying a very low dose of a single medication to augment the fish oil. If this result sticks, she would be one of my first patients, over several years of discussing fish oil with most of my patients, to get to near-zero medications by using fish oil. And we have to wait to see if this result will stick. [Still doing okay as of December 2005]. That might give you some idea of the relative power of this approach, as best we can tell at this point: looks like it does something, but rarely enough to allow taking no mood stabilizers at all.]

Notice the emphasis in the research studies on depression, versus bipolar disorder. There is a report of hypomania developing while on omega-3'sKinrys (and in the Harvard study as wellStoll), although whether the fatty acids were the "cause" of this episode is of course not certain.

Conclusions (reviewed as of 1/2006; still seem to hold):

the evidence is piling up that omega-3 fatty acids do something, at least in some people;

the dose to use is not at all clear, as some studies suggest you can go too high and lose benefits (Nevets, Sagduyu), whereas many of the individual glowing results come with the higher doses;

even at higher doses, the risks seem minimal, and there may actually be additional benefits (on cholesterol, perhaps arthritis);

however, it's a large number of pills, though a minimal-moderate expense;

many patients report fish burps (try sticking the pills in the freezer between doses, and take them with meals), rarely oily diarrhea, and no other bad effects; and finally

it's also not clear how long you have to wait to see benefits, but especially with the smaller doses they may take 1-2 months to show up, so if you take them, prepare yourself for a period of taking a lot of pills with no benefits.

Do I recommend them to my patients? Yes, rather commonly, especially when we're looking for all possible anti-depression tools to use, rather than have to use a typical antidepressant. I still have yet to see a clear-cut stunning improvement like those case reports in the table above, but because the risk appears to be so minimal, in many cases it seems like it's worth a try.

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