Topiramate (Topamax)

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People keep writing me, one every few weeks (not a tidal wave or anything) and saying they really like topiramate, why don’t I sound more enthusiastic about it, etc. Please note: the way for the rest of us to judge a medication’s effectiveness is not based on your personal results.  If you’re on it and it’s working, that’s great!  Don’t consider stopping just because you read here that it has not been shown in “randomized clinical trials” to be more effective than placebo.

Indeed, as you’ll see below, research evidence it does not strongly support use of topiramate has a “mood stabilizer”.  However, it seems like about once a month someone writes me and says that it was tremendously helpful for them.  You’ll see below that the evidence is not entirely negative.  This is a medication where comparing the potential for benefit versus the potential risks is quite tricky.  You can find strong opinions on both sides.

Nevertheless, in general the best way to judge a medication’s effectiveness is to compare it to a placebo (randomly assigning people to the medication, or the sugar pill — thus the term “randomized clinical trial” (read more about randomized trials as a superior kind of evidence; that link refers to treatment of panic disorder but it could be any treatment — including in this case topiramate).  In January 2006 the Cochrane group, a highly respected team that evaluates the effectiveness of treatment based on randomized trial reslts, concluded there was not sufficient evidence to recommend topiramate as a treatment for bipolar disorder.Vasudev Even the manufacturer published a paper saying it didn’t work in bipolar disorder (treatment of mania, in this case), and that lithium was better.Kushner

Or rather, that’s where we were until this report — from my December 2005 update: However, now comes a comparison trial of topiramate versus valproate (Depakote) for the treatment of Bipolar I mania, when added to a relatively low dose of an atypical antipsychotic, risperidone.Bahk  These data could support a major shift in strategy, away from valproate as a mainstay mood stabilizer, because of the associated weight problems (2.5 kilogram gain in this 6-week study), as they so often are seen in practice); toward a medication whose effectiveness is in serious question but which does not have the weight-gain problem.  This would seem foolish — except in light of the results in this study, where the topiramate + risperidone group did as well as the valproate + risperidone group.  And the topiramate + risperidone group had no more significant nor serious side effects, while their weight stayed stable (half lost a little, the other half did not).  This re-opens the case for consideration of topiramate as  a mood stabilizer, in my opinion, but we’ll need more data now. 

A reader wrote and complained that I was unfairly negative about topiramate when she had improved tremendously on it: 

“I have been on Topomax since April of this past year and it RADICALLY CHANGED MY LIFE!!

For 30 + years I was impulsive, negative, moody, depressed, suicidal, hearing voices, too many thoughts to get straight in my mind, quitting jobs, church-hopping, unstable, a MESS!

Finally, when I got diagnosed and the doc wanted to put me on Depakote, I did some research and opted OUT of that idea and decided to try Topomax instead, due to the weight loss properties.  Within 30 minutes, it was quiet in my head, I could focus, I was peaceful, happy, signed up to head to college for a career, joined back up with the former church I had left, rekindled all my old relationships that ended due to bad communication with people.

I have had no side-effects from the medicine, other than occasional tingling in my lips.”

But she agreed that she made her medication choice not based on evidence for effectiveness, but rather by choosing among side effect risks. Rather than go with Depakote, she chose topiramate because with it frequently causes weight loss, whereas with Depakote often causes weight gain. In my experience with topiramate, she got really lucky as far as effectiveness goes. Can’t hardly argue with her outcome: great benefits, minimal side effects. I wish this happened more often with topiramate; it would be an obvious top choice. 

This medication clearly can decrease appetite and lead to weight loss, as is now even more certain following the publication of a large British study comparing it to placebo.Wilding In this study, all patients were part of a weight loss program.  Even the patients on placebo lost weight, almost 2% of their body weight, which may not sound like much, but these folks had to be quite overweight to get into this study.  But the folks on about 100 mg of topiramate lost 7% of their body weight in a year, and more if they were on higher doses, as shown here:      

Dose% of weight lost (1 year)Lbs. lost (if 250 lbs or more to start)Lbs. lost (if 300 pounds or more to start)
100 mg 71520
200 mg92327
250 mg102530

So, there is not much doubt that this stuff helps people lose weight.  But there are two problems with it. 

First, it does not appear to be a mood stabilizer, except for that new study up there by Bahk.  Or perhaps we should put it this way: it does not appear to be an effective anti-manic in Bipolar I (with four research studies showing it was not better than placebo in this roleKushner). That leaves open the possibility that it might do something useful in non-manic versions of bipolar disorder (like Bipolar II, the type most of this website focuses on).  And it might have some significant antidepressant action though, as much as Wellbutrin, an antidepressant, in a recent comparison study.McIntyre

Secondly, it has lots of side effects.  It can cause depression (listed as such in the PDR); it can cause anxiety, quite frequently in my experience; and about 1/3 of patients get cognitive impairment (not to mention to 1.5% risk of kidney stones, a lower risk of glaucoma, and a rare risk of “metabolic acidosis”, a potentially fatal blood chemistry change).    

Revised 9/2007:  This medication has some role in appetite management in select cases. A recent study showed that it was better than placebo for weight control when patients were taking olanzapine (Zyprexa), and the benefits continued for over a year.Egger  But I do not routinely use it for bipolar symptoms.  It’s just too unpredictable and too loaded with really impairing side effect potential.  Here are some thoughts about topiramate dosing.  See also Dr. Ivan’s extensive presentation.Goldberg(c) and the FDA warning on glaucoma

(updated 3/2007)

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