Q:  How Safe is an SSRI with Zyprexa and Lithium for Someone with Manic-Depression?

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.

-Tony


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.

Dr. Phelps