(revised 10/2016)

This medication wouldn’t even be on the mood stabilizer map except for the fact that it causes weight loss, where so many medications for bipolar disorder cause weight gain. For example, in a large study where everyone received diet counseling, half of the group took zonisamide and half took a placebo. The zonisamide group lost 6 kg (13 pounds) in 4 months while the placebo group lost 1 kg (about 2 pounds).Gadde

But does it work?

Update 10/2016.  For bipolar depression: no.  A randomized trial at the NIMH designed specifically to look at this question found no difference between zonisamide and placebo. Dauphinais 

Old text follows for those want all the prior references, including those on weight loss

A fairly large “open trial” (no control group; usually makes the medication look better than it will look later) of this medication was strongly positive.McElroy They lost weight as expected. There is also a small open trial in bipolar depression, just 10 patients, but a significant improvement was seen.Anand However, there is also a case report of mania induced by zonisamide,Charles though causation in this illness is always hard to establish. In the McElroy study, 20% of the patients dropped out because their mood was worse. Of course, mood with this illness can get worse on its own, which might account for some of those who worsened. So far in just a few patients, I’ve not seen it make mood worse. But nausea…

These studies used a starting dose of 100 mg. When I started patients at that dose, 3 in a row had so much nausea they couldn’t continue. Since starting people at 25 mg (the next few in a row; I haven’t used it much yet, as of 2006), no one has had trouble with nausea. All were able to reach 300 mg or more. One patient did very well on it, better at 500 mg than at 400 — but she couldn’t talk properly at the higher dose, and couldn’t think straight (“cognitive impairment”, a recognized side effect).

Okay, so what are the risks?

By the time you get to this page you’ve probably also learned about lamotrigine (or you should have, since lamotrigine is much more widely used and studied, so on that basis may be somewhat safer). The same rash problem — “Stevens-Johnson syndrome” — that is the main risk for lamotrigine is also a significant risk for zonisamide. If you’ve ever had a rash on a sulfa medication, like Bactrim or Septra, then you are at a much higher risk if you try zonisamide.

It can also change kidney function and cause kidney stones. This is not a complete list of the risks, just some of the big ones. Cognitive impairment, such as my patient experienced, is a recognized side effect.