Depakote & Extreme Fatique,Would Folate, B Vitamins Help?
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Q:   Depakote & Extreme Fatique-Would Folate, B Vitamins Help?

My 17yr old son is on 2000mg depakote er . Takes 1500mg at bedtime and 500mg in am. His blood level is 82 which has subsided his symptoms. At 1500mg he still had alot of unpredictable agitation his blood level was at 68. He is mixed state rapid cycler bipolar 1 . Problem extreme fatigue after school sleeps for 2-3 hours always difficult to get up. Can folic acid B vitamins counteract this side effect? what can? It is very disturbing when he cycles he is not safe he runs away takes dangerous risks .He is stable now just way too sleepy. He attends activities fully away from this sleeping.  Suggestions Please

Dear Lori -- 

Sorry to hear that a medication which seems to be so critical it is causing this kind of trouble:  it must be frustrating to watch, wanting him to be able to function better, and sleep less mid-day, while knowing that such risks lie on the other side, toward lowering the dose.

Folate for this problem? I have not heard of this idea. However, just lately I have been hearing more about folate and the related compound, homocysteine (for more on how they are connected, see below*). Just recently, interest is growing in homocysteine as part of a possible connection between mood problems and cardiovascular risk, but it is also being examined for a connection to cognitive abilities. For example, here's an article (
Osher) which concludes thus:

The findings of this study confirm that in euthymic bipolar patients, higher homocysteine levels are associated with poorer performance in some neuropsychological tests. Treatment trials will be required before it will be known if the putative decrements in the executive function of bipolar patients can be reversed, or at least retarded, if homocysteine levels are reduced (as, for example, by dietary addition of B vitamin supplements).

In other words, in patients with bipolar disorder whose mood is well controlled, those who had higher homocysteine levels did not do as well on some basic tests of thinking abilities, but it has not yet been shown that treatment -- such as with folate, a B vitamin --, can reduce those levels and therefore potentially improve this cognitive function problem.

Similarly, there is some limited evidence associating low levels of folate with depression (Taylor, Gilbody). But in searching around on this topic I did not run into any evidence suggesting that folate might help directly with this fatigue/daytime sleepiness.

On the other hand, because supplementation with folate is a common treatment, primarily for women considering pregnancy who might be at risk of low folate levels, one good reason that there might be a little harm in trying it  (e.g. see
Health risk of too much folic acid -- which is minimal --from Wikipedia; however, read the section about folate and B12, and the need and some people for a B-12 blood test before using folate). That might be easier than figuring out whether the evidence really supports this idea, unfortunately.

Dr. Phelps

*(the connection between folate and homocysteine: This is a little tricky, but if you really need to know for some reason, I'll give you a reference here in a moment. Basically, homocysteine and methionine are connected in a circular loop in which a methyl group (think of this as a single carbon atom and its associated hydrogen atoms, traveling together) is donated by a folate-related compound. Because of this donor role of folate, without that b-vitamin, this conversion of homocysteine to methionine is inhibited. The result is higher homocysteine levels. Currently it is presumed that the way folate lowers those levels is by participating in this chemical reaction of converting homocysteine to methionine. Fun, huh,?

Published November, 2007

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