Olanzapine versus risperidone in bipolar disorder
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Olanzapine versus risperidone in bipolar disorder

Q: My Doctor wants me to take olanzapine instead of risperidone, i recently had a breakthrough episode of mania. At the end of the day is there anything to choose and if so what. Basically i need a medical opinion on the merits of olanzapine over risperidone. Can you help? many thanks in anticipation.

Dear Hugh --
This is a very appropriate question.  I think there are some very hefty differences, myself.  Olanzapine has been approved by the FDA as a "mood stabilizer", based on numerous studies showing it treats bipolar I as well as a lithium comparison treatment.  Nothing like that has been done for risperidone.  When risperidone first came out, there quickly appeared several case reports of it inducing mania, much in the manner that antidepressants can do.  In my experience, risperidone is a pretty darn good antidepressant: I've given it in microdoses, e.g. 0.5 mg twice a day (even 0.25mg once in a 45 year old woman who could get apparently hypomanic after two doses at 0.5mg!), and I believe I have seen rapid relief of depression, as well as relief of racing thoughts and insomnia.  In my view, based on this kind of thing, I use it only with great caution in bipolar disorder.

So, it was with great surprise that I read a recent article by some serious mood experts basically concluding these two medications are both good, and both about the same as far as risk of inducing mania.  In fact, I was shocked: who did they study to get this result?  I've had about 3 patients in about 300-500 people get really agitated (actually a sort of increase in OCD-like thoughts and agitation/anxiety; not really very much like the rather more typical increase in hypomanic symptoms risperidone seems capable of kicking off).  I think I've seen far more than that get hypomanic or worse on risperidone, especially at >2mg/day.

The article is A naturalistic comparison of clozapine, risperidone, and olanzapine in the treatment of bipolar disorder by Guille, Gary Sachs (head of the Harvard Bipolar Program), and Ghaemi.   Here's the abstract.  Note that this is folks with bipolar I.  I'm not sure if that's the difference, i.e. they studied bipolar I and most of the trouble I've seen has been in bipolar II.  Or maybe they used a different conception of hypomania, and that's why they didn't see people getting it.  In my view, risperidone should be used with great caution.  There's renewed enthusiasm for it these days for two reasons: 1) it doesn't cause the tremendous weight gain of olanzapine, and attendant risks; and 2) Janssen, the manufacturer, is spending a lot of money plugging this difference in risk (I can't remember; they may have paid to support the authors' research on which that article is based.  This doesn't mean the authors are crooked or even just biased; it just means Janssen is paying for research that they know will make their product look good).

You touched a nerve there, didn't you?  Good luck.

Dr. Phelps

Published November, 2000

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