Q: Can antidepressants cause highs even when a mood stabilizer is on
Is antidepressant-induced hypomania/mania an
example of "kindling"?
Does having a mixed state mean that you have
Bipolar I, not Bipolar II?
Hi Dr Phelps,
can't find an answer for this in the archives.
have been Bipolar II for several years now and did very well on Lithium and
Zoloft for quite a while. Zoloft was decreased down to 25mg, but then the
depression set in again. Zoloft was increased to 100mg and I progressed rapidly
to hypomania then a mixed episode. I was ripped off the Zoloft. Tegretol and
Risperdal were added to the Lithium. I was left on the Tegretol and Lithium
after it all settled down. A recent spell of depression occured again, although
not very bad, I was given 50mg Zoloft. This time I emerged from the depression
quickly again and felt fantastic with high energy levels. My psychiatrist
removed the Zoloft promptly to prevent another high.
questions are: can antidepressants cause highs even though mood stabilizers are
on board?. Is this an example of what you call kindling? Does having had a
mixed episode mean that I have Bipolar I rather than Bipolar II?
Thanks so much for your time
Dear Ms. H. --
questions one at a time:
antidepressants cause highs even when a mood stabilizer is on board?
In the opinion of
most mood experts, in fact almost universally, the answer is yes. However,
there are still a few non-believers whose skepticism should not be entirely
ignored. It is just very difficult to establish whether an antidepressant is
truly responsible for a manic episode. How does one know that manic episode
wasn't just going to happen on its own?
On the other
hand, if manic symptoms begin 4 - 7 days after an antidepressant is added, and
then diminish when antidepressant is removed, that does very strongly imply the
antidepressant was responsible. Ideally, we should have a randomized trial in
which some people on a mood stabilizer are given an antidepressant, and others
are not. There is one such trial, recently published (Sachs
et al), but only 14% of the eligible patients actually enrolled. All
sorts of speculation have been offered as to the kinds of bias that could have
been introduced in this study because of that opportunity for "selection
pressure", in which only certain kinds of patients were enrolled. For example,
perhaps only those whose physician felt that trying an antidepressant would be
safe were allowed to enter. All of those who might have had more negative
reactions to antidepressants in the past, such as you have had more recently,
might have been excluded. In that case, we expect the study to show that
antidepressants were not particularly bothersome for patients, and that is what
was shown. They were no worse off on antidepressants than they were on a
placebo, in terms of inducing manic symptoms. (Interestingly, neither did they
respond to the antidepressant better than a placebo.
This has created
all sorts of consternation, because most clinicians are fairly convinced from
their experience that antidepressants do indeed have considerable power in
bipolar depression. The problem is just the same one that you have experienced:
when an antidepressant is added, sometimes it seems to be directly responsible
for a dramatic push into work toward manic symptoms. So, finally, to summarize:
yes, I think nearly everyone believes that antidepressants have this capacity,
even when a mood stabilizer is in place.
antidepressant-induced hypomania/mania an example of "kindling"?
In a word, no.
"Kindling" refers to a theoretical idea that episodes of antidepressant-induced
hypomania/mania could increase a person's potential for having manic symptoms on
his/her own. In other words, perhaps antidepressant-induced episodes might act
like real episodes (with no antidepressant around at all) do: in some people, in
fact in many people with bipolar disorder, it appears that episode frequency and
intensity can accelerate over time. Particularly in bipolar I, one can see a
pattern in which people might have years in between episodes when they are in
their 20s, but have much more frequent episodes in their 30s. It appears as
though episodes can be get episodes: each one making subsequent episodes more
likely to occur, and more severe when they do occur.
The question with
"kindling" is first whether this pattern is truly associated with the episodes
themselves (which we probably will not know until we have a better biologic
understanding of what causes these episodes); and secondly whether
antidepressants can cause the same kind of "push forward" that naturally
occurring episodes seem to, in some people.
3) Does having a
mixed state mean that you have Bipolar I, not Bipolar II?
but in practice, mood experts around the world have been very consistent in
recognizing that bipolar II can have mixed states (e.g. a
recent summary on this issue by Vieta
and Suppes) -- so in terms of present-day understanding, having mixed states
does not really shift your diagnosis one way or another.
Thank you for
interesting questions, all of which demonstrate that you have been doing quite a
bit of self-education.
Published July, 2008