(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.
NO SHORTCUTS
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.
Weight loss can be achieved either by eating fewer calories or by
burning more calories with physical activity, preferably both.