How Safe is an SSRI with Zyprexa and Lithium for Someone with
I have tried everything under the sun for getting bipolar depression (depression
and mixed states/dysphoric mania) under control. This includes anti-convulsants
(Tegretol, Depakote, Lamictal, Neurontin), fish oil, and thyroid supplements,
and combinations thereof. The only thing that has worked has been a combination
of paroxetine (40mg), Zyprexa (10mg), and lithium (675mg). I also have a problem
with an anxiety disorder which the paroxetine helps with also. I have tried
reducing the paroxetine, but the anxiety returns.
I know you argue (on this site and in your book) about not using AD's for
bipolar disorder. But will using two mood stabilizers with the AD reduce the
risk of worsening kindling? I am very curious. Thanks.
Dear Tony --
First of all, we should be clear on one thing: "kindling" is a theoretical
concern about a possible effect of antidepressants on patients with bipolar
disorder. It would be very difficult to come up with some kind of research
approach to actually test this theory, because it would require following
patients over many years. That alone is not so hard to do, and a few studies are
doing it, but to randomize people to either receive an antidepressant or not,
and then require them to remain in that relatively "pure" state for years, is
beyond the reach of any research program currently underway.
Therefore, we must all except that the "kindling" concern is likely to remain an
open question. Perhaps someday we will have a biologic marker that reflects
possible changes induced by antidepressants; or some other marker of bipolar
disease progression. These could then be used to address this open question.
Meanwhile, then, there are people like you who end up on antidepressants on an
ongoing basis. Even Dr. Nassir Ghaemi, who like me is very concerned about
ongoing antidepressants, and has a lot more academic credentials behind him,
recognizes that perhaps as many as 20% of patients with bipolar disorder will
need an antidepressant as part of their continuing treatment.
Therefore, you are anything but a loner in this respect. And whether there is
some accumulating risk to you from remaining on antidepressant is a wide-open
question which we should not necessarily assume portends risk for you. I have
made lots of noise about the potential risks of antidepressants not so much to
alarm people like you but rather to raise awareness amongst prescribers that as
many as 80% of patients with bipolar disorder can be managed without
antidepressants, so that if there is a risk, it can be avoided. I confess, I
have also tried to raise awareness that there may indeed be a risk, because many
practitioners operate as though antidepressants are relatively risk-free
compared to mood stabilizer options. As you have read, even without the concerns
about "kindling", there are plenty of reasons to worry about antidepressants in
patients with bipolar disorder. However, as you make fairly clear in your
letter, for people like you who have explored alternatives and tried doing
without them, and then clearly do better on them, continuing antidepressants is
definitely a rational option.
As to whether having more mood stabilizers on board might present some
"insurance" against adverse effects on antidepressants, and it is my impression
from the literature that this may indeed be true: the potential for "switching",
from depression and to mania, for example, seems to be substantially greater
when people are not taking a mood stabilizer. One of the best mood stabilizers,
olanzapine (Zyprexa), seems to nearly eliminate the potential for switching when
it is combined with fluoxetine (the combination is called Symbyax). Although the
weight gain from the olanzapine component makes this a generally impractical
strategy, it does suggest that a powerful mood stabilizer -- such as one might
be able to achieve by combining several potentially weaker ones -- is protective
in some way.
Published July, 2007