Q. I am taking Depakote and have gained a lot of weight from it. I have heard of a drug called Topamax that is also a mood stabilizer but people don't gain weight on it.

I was wondering how you felt about Topamax.

A. The questions about weight gain on anti-epileptic agents is a very good one, particularly since so many folks are on these agents. The anti-epileptics include Tegretol (carbamazepine), Depakote (valproate), Neurontin (gabapentin), Lamictal (lamotrigine), and Topamax (topiramate). These agents were patented for treatment of seizures, and were found (accidentally) to have the ability to decrease mania and manic-like episodes. There are other agents used to control seizures that have been utilized in psychiatric disorders, but these are the ones most frequently used. The anti-epileptics are frequently referred to as mood stabilizers, albeit there is little data to suggest they do anything but stop mania. In fact, there is a large body of data that indicates they worsen depression. The vast majority of patient with mania do not have seizures, so these agents are likely working through some other mode of action than seizure control.

Depakote was the first agent since lithium, to actually do studies and gain FDA approval for use in manic patients. There is no right or wrong dosage of Depakote in mania. There are certain blood levels which need to be obtained to decrease seizure frequency, and these same levels are used to determine adequacy of dosage in manic patients. An Italian group showed that Depakote initially causes an increased transport of tryptophan, the precursor of serotonin, into the brain. This stabilizes mood. Unfortunately, this eventually depletes serum tryptophan levels, and the only way to then get enough tryptophan into the brain is to eat carbohydrates (candy, chocolate, pasta, cookies, bread, etc.). The sugars and subsequent insulin release cause an increased uptake of tryptophan by the brain from the diminished supplies in the blood stream. This eating borders on uncontrollable for many folks because there is a biological drive to eat. The bottom line is weight gain.

Topamax is not supposed to have as much or any weight gain. Controlled trials in patients with seizure disorders indicates weight loss in 7-12% of patients using Topamax, and no report of weight gain. We do not know if the same will happen in bipolar patients or not, but there is reason for optimism. Preliminary studies do indicate the drug works fairly well in bipolars, albeit not for everyone, and there is no problem with weight gain. It is worth discussing with your physician if weight gain is a problem on Depakote. There is no data on the efficacy of Topamax in borderline personality disorder that I am aware of at this time.