Epilepsy drug leads to weight loss, side effects

NEW YORK (Reuters Health) – A drug approved to prevent seizures may also help obese people lose a few pounds when it’s added to therapy and nutritional guidance, a new small trial suggests.

But people who took zonisamide also reported more side effects, from nausea and vomiting to anxiety and depression. And two researchers not involved in the study questioned how much the drug would actually help people in the real world.

Although zonisamide is only approved by the U.S. Food and Drug Administration for seizures, doctors can prescribe it “off-label” for non-approved purposes. Prior small trials and anecdotal evidence suggested it might help heavy people shed extra pounds.

“There is a little bit of weight loss with this drug when it is given for treatment of epilepsy,” said lead researcher Dr. Kishore Gadde, from Duke University Medical Center in Durham, North Carolina.

That could be because of its effects on serotonin and dopamine, he said. Those two neurotransmitters are known to effect motivation and reward pathways in the brain, including those related to food.

Gadde said his team wanted to see if zonisamide could produce weight loss in people without epilepsy, and with the added help of a behavioral intervention.

According to disclosures published with the study, Gadde has multiple patents for zonisamide as a treatment of obesity and weight gain, and he owns equity in a company developing a combination weight-loss drug containing zonisamide.

For the new study, funded by the National Institute of Diabetes and Digestive and Kidney Diseases, Gadde and his colleagues randomly assigned 225 obese people to take either 200 or 400 milligrams of zonisamide or a drug-free placebo pill every day for one year. On top of that, all participants met regularly with a dietician and were encouraged to be more physically active.

At the outset, they had an average body mass index – a measure of weight relative to height – of 37.6. That’s the equivalent of a five-foot, six-inch person weighing 233 pounds.

One year later, people assigned to the placebo had lost an average of nine pounds, and those on the lower zonisamide dose had dropped ten pounds. Participants taking the higher daily dose had the greatest average weight loss, at 16 pounds.

Side effects were most common in the high-dose group. Out of 75 people, 10 reported nausea or vomiting, 14 had headaches, 15 developed infections, eight had impaired memory and seven reported anxiety.

Gadde said it’s not clear which of those were directly related to the drug, or how much they bothered patients. Between four and six participants in each group, including the placebo cohort, dropped out because of side effects.

According to an FDA-mandated warning on the drug’s label, zonisamide can cause serious skin rashes, suicidal thoughts and problems with memory and thinking, among other possible side effects.

In its generic form, the drug can be bought for about $30 per month.


Obesity researcher Dr. Raj Padwal, from the University of Alberta in Edmonton, Canada, said the difference between the high-dose zonisamide and placebo groups in this study was “modest” at best.

“Overall it’s kind of a ho-hum result,” Padwal, who wasn’t involved in the new research, told Reuters Health.

“The earlier studies of zonisamide were a little more promising, so I would characterize this as a bit disappointing.”

Dr. Yoni Freedhoff, from the University of Ottawa in Canada and the Bariatric Medical Institute, also said he wasn’t incredibly impressed with the extra weight loss with zonisamide, especially because the study only lasted one year.

“Although that sounds like an awfully long time, it’s not when it comes to weight management. It’s keeping the weight off that’s a struggle,” he said. “To be useful for clinical management of people who struggle, we need to see whether two, three, four, five years down the road, there’s actually any benefit.”

What’s more, Freedhoff added, it seems unlikely based on the data that zonisamide would have any effect on cholesterol levels or diabetes risk.

“At the end of the day, there just aren’t any shortcuts,” Freedhoff, who also didn’t participate in the study, told Reuters Health.

Gadde said much larger studies, with hundreds or thousands of obese people in each treatment group, will be necessary to more clearly see the weight-loss benefits and possible risks of zonisamide. He plans to ask the National Institutes of Health if they will fund him to do that research.

“The more options that we have available, the better it’s going to be for clinicians as well as the consumers,” Gadde told Reuters Health.

A combination drug including a different anti-seizure medication, topiramate, was approved by the FDA for weight loss in July.

Freedhoff said zonisamide may be useful for people who need anti-seizure treatment but are on other epilepsy drugs that make them gain weight.

“Have a discussion with your doctor, not about whether there’s a magic bullet you could be on for weight loss, but whether or not you’re on any medications at this point that could be contributing to weight gain” when there’s an effective alternative, he advised.

SOURCE: http://bit.ly/TuOztq Archives of Internal Medicine, online October 15, 2012.

Epilepsy drug leads to weight loss, side effects
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