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Q: Depakote & Relapse in Bipolar Disorder
Dear Dr. Phelps,
I have been reading that the efficacy of the long term use (more than 3 months)
of Depakote in the treatment of BP is not yet established.
Why cant one stop the medication after a manic episode has subsided and after
continuing treatment for around 3 months, and restart if one feels the symptoms
coming back.
I had my first manic episode recently triggered by an extremely stressful
situation in my personal life and have also been diagnosed as having
hyperthyroidism. Could the mania and mood swings be just the hyperthyroidism
coupled with stress? I am very stable now and on methimazole too. Do I need to
continue my depakote beyond three months. I am worried about the hepatotoxicity
and and other side effects.
Lastly, will avoiding stressful situations prevent further episodes or are they
inevitable?
Dear A' --
You're right, Depakote has not been shown to prevent relapse in bipolar disorder
in the way that we would like to see: multiple large randomized trials showing
that people who keep taking Depakote relapse into bipolar symptoms less than
those taking placebo. There is only one large study like that
Bowden and the results were confusing, perhaps because even the
placebo group did quite well, which has been thought perhaps related to the way
in which the patient were recruited into the study, so that there were a lot of
relatively healthy folks in there who just didn't relapse very much, no matter
what they were taking (lithium or Depakote or placebo).
However, even before that study we were recommending
that patients with bipolar disorder stay on Depakote after their symptoms got
better, and here's why. It's basically an extension of what we do know
about lithium. You see, people figured out without a lot of formal research
that Depakote seemed to act rather like lithium in bipolar disorder. And
lithium has been shown to be an effective agent when taken to prevent
relapse. And after all, we know that bipolar disorder does recur,
that's not in doubt. In some people, when it recurs it can be disastrous. So,
if we have reason to believe that Depakote might prevent relapse, like lithium
does, then even without the formal research studies we would like to have (the
ones that you are pointing out that we don't have), we recommend staying on
it.
The important point: we don't have studies saying
Depakote doesn't work either. We just don't have, as you point out,
studies saying it does. We think it does, we just don't have the studies
to confirm that yet (because doing such studies requires a tremendous amount of
money and effort, the kind that takes some big money -- so if the company, like
Abbot Labs who makes Depakote, doesn't see the financial benefit in funding such
a study, and they're a pretty small company that has to be pretty careful with
this kind of thing, then that research is not going to get repeated (they helped
fund the Bowden study).
One last note: the studies showing lithium works are
"robust", as they say in the research lingo. People who take lithium relapse at
one third the rate of those who take placebo in the existing studies, according
to a very large review (Cochrane
Database).
Wait, one more note, after another literature search:
there is a new update of the Bowden studyGyulai
showing that Depakote prevented relapse into bipolar depression better
than lithium did. I haven't read the text yet but that could change the tune at
least a little. (If I understand the abstract correctly, this would be called a
"secondary analysis" and those are not generally regarded as quite as strong a
statement as the original study cited above). Dr. Bowden's recent summary
(here's his
abstract) of this issue also seems to emphasize the value of valproate and
lithium for prevention of mania; the lack of strength of lithium's effect in
preventing depression; and the value of lamotrigine as being stronger than
lithium for the prevention of depression.
That's a good question you asked. Just to be clear:
there is very strong consensus in psychiatry that staying on is smarter than
going off -- no controversy around that to my knowledge. So, careful if you
start deciding to go the other way just because we don't have the formal data
supporting it; there could be some pretty good "clinical experience" supporting
this practice. That's not to say we should keep thinking though; so good on ya'
for asking, and thinking.
Dr. Phelps
Published December, 2003
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