Can tweaking Americans' neurochemistry slide the nation's scales down a few pounds?

        Researchers are studying several antidepressants as potential treatments for obesity, and here in Cincinnati, one researcher is studying whether a medication commonly prescribed to treat epilepsy and bipolar disorder can also treat binge eating disorder.

        The studies come as researchers are trying to untangle the link between mood, food and America's obesity epidemic. Six out of 10 Americans are overweight or obese, according to federal health statistics. In the meantime, there's considerable debate as to how crucial decoding the brain's chemistry is to weight loss.

        At UCPhysicians Weight Management Program, Dr. Susan McElroy is studying the effectiveness of Topamax (topiramate) — an anticonvulsant often prescribed to control epileptic seizures, and to stabilize mood in patients with bipolar disorder — to treat binge eating disorder. Dr. McElroy has also studied several antidepressants to see whether they can be effective against the disorder.

        So far, the results look good, she said.

        A 14-week study showed that patients who took Topamax lost an average of 12.98 pounds in that time, compared with patients on a placebo who lost an average of 2.64 pounds. Patients were encouraged to keep diaries about how much they ate and how they felt, but they didn't receive any nutrition counseling and were not put on a weight-loss food plan.

        Dr. McElroy started studying the drug after observing that bipolar patients who were taking it to control their mood disorder reported that it seemed to suppress their binges.

        “The study shows that it works, but we don't know why,” she said.
       

Successful prescriptions

        Linda Burchett, 40, of Fort Thomas signed up for the UCPhysicians study after reading an article about the link between depression and overeating.

MOOD MEDICATIONS

These are a few of the drugs now being used to treat obesity but normally are used for other health issues.     Topamax: An anticonvulsant prescribed to prevent epileptic seizures and as a mood stabilizer for people with bipolar disorder. The drug is believed to alter the neurochemical signals that cause seizures and it is reported to control binge-eating in bipolar patients.     Prozac: An antidepressant prescribed for depression, bulimia nervosa and obsessive-compulsive disorder. Prozac stabilizes levels of the neurotransmitter serotonin in the brain, helping patients overcome depression and harmful behaviors. It can cause short-term weight gain by itself, and may help depressed patients who are also obese seek out and stick to a weight-loss regimen.     Paxil: An antidepressant prescribed for depression, obsessive-compulsive disorder, panic disorder, generalized anxiety disorder, and social anxiety disorder. It can cause weight gain, but is thought to control emotional impulses that contribute to binge eating.     Effexor: An antidepressant prescribed for depression and anxiety that stabilizes serotonin and norepinephrine levels in the brain. Helps control emotional impulses that contribute to binge eating.

        She never considered herself depressed; she thought she was just tired and stressed. But she knew food was too important in her life and wondered why every meal “felt like my last meal,” a mind-set that compelled her to overeat.

        Ms. Burchett is taking the antidepressant Prozac (fluoxetine) and antianxiety drug Effexor (venlafaxine) along with Topamax. Prozac affects serotonin — a “feel-good” neurotransmitter in the brain. Effexor acts on serotonin and norepinephrin levels. In the last year, she's lost about 35 pounds, and her Body Mass Index has decreased from 39 to 33. She doesn't exercise consistently and she's not on a diet. “I try to follow the food pyramid, but I'm not tracking every bite,” she says.

        The Topamax has made the most difference in suppressing her appetite, Ms. Burchett says.

        “Now I pretty much just eat out of hunger. I eat slower. I eat more in proportion to what I want. I think I feel a more normal relationship between food and hunger, not food and a way to control my feelings.”
       

Higher self-esteem

        Charles Van Sant, 47, of Delhi Township, has struggled with depression since his mother's death in 1992. He signed up as a patient at Dr. McElroy's program in February and started taking the Effexor in March. He's only lost about five pounds, but he feels much better about life.

        “I feel an incredible difference in my self-esteem, my general feelings about myself, my lot in life,” he says.

        At 6-foot, 3 inches and 380 pounds, he says, “I have a long way to go” losing weight.

        The Effexor hasn't made that much of a difference in his eating habits, Mr. Van Sant says, but it has made him hopeful that he can lose weight.

        “I know I binge. I know I do. I find that if I'm really stressed, I have this insatiable need for peanut butter. I'll eat a couple of pieces of bread with some peanut butter. Why that works, I don't know, but I feel better,” he says.
       

Body chemistry

        Most weight loss advice boils down to two simple directives: Eat less. Exercise more.

        But obesity is more than a simple equation of calories consumed and calories burned for some men and women. Hormonal factors play a part in how the body metabolizes food, particularly for people with diabetes.

        Other hormones play a role in regulating appetite. A study in the May 23 New England Journal of Medicine showed that gastric bypass surgery drastically reduces the amount of ghrelin, a hunger-regulating hormone produced in the stomach. Less ghrelin translates to more permanent weight loss, which explains why patients who undergo gastric bypass surgery (“stomach stapling”) are more likely to lose weight and keep it off than people who follow conventional weight-loss plans, say researchers at the University of Washington and the Veterans Affairs Puget Sound Health Care System.

        Brain chemistry also plays a significant role in emotional eating patterns. Current medical wisdom suggests that eating carbohydrates produces serotonin, which theoretically, explains why some people eat when they're depressed.

        Medications such as Wellbutrin can give overweight people who are also depressed enough of a boost to let them make the lifestyle changes that can lead to weight loss, says Dr. Louis Arrone, director of the Weight Loss Program at Weill-Cornell Medical Center in New York.

        “I think it's hard to concentrate on diet and exercise when you're depressed,” he says.

        He estimates that about 45 percent of the people who seek treatment for obesity are depressed. Another 30 percent of people who seek obesity treatment show some symptoms of binge eating disorder.

        Dopamine, another neurotransmitter that regulates pleasure, also comes into play in obesity and overeating. Repeated use of addictive drugs and, for some people, food, all increase dopamine levels in the brain, theoretically leading to addiction as users seek to replicate the “buzz” dopamine gives them.

        Researchers at Brookhaven National Laboratory in Upton, N.Y., found last year that obese people have fewer dopamine receptors in the brain — just like drug addicts.

        A study released earlier this month at Brookhaven found that just the smell and taste of food increased dopamine levels in hungry people's brains.

        Studies have shown Wellbutrin to be effective for weight loss, when combined with diet and exercise. The drug has been approved for use as an antidepressant and a smoking cessation aid, but not for weight loss.

        And some researchers are exploring the combination of Meridia (sibutramine), a popular prescription appetite suppressant, and Prozac (fluoxetine), for weight loss.

        Such research suggests that medications that regulate serotonin and dopamine production can curb overeating, at least in people who are “addicted” to food.
       

Behavioral therapy

        But not everyone who's overweight is depressed, and some depressed people actually lose weight as they lose interest in food. There's also some concern that research into mood and food could have chubby Americans lining up for antidepressants the way they used to line up for phen-fen.

        Since more than 60 percent of Americans are overweight or obese, that could present problems.

        Dr. Linda Stetson, a University of Louisville researcher and expert on the link between diabetes and depression, says medication should take a back seat to behavioral therapy, or teaching overeaters how to cope with situations that make them want to binge eat.

        “It's really a problem of excess and fat and the ability to do stuff without any physical exertion. If you combine that with the stress of our daily lives that make you in a high risk situation for overeating, that really escalates the potential for obesity to get worse,” she said.

        Dr. Stetson and many other experts feel obesity in America is a cultural issue, as well as an individual struggle. “I think it's a public health crisis. In some ways, it's hard not be to driven to obesity in this culture, with a McDonald's on every corner and no (physical education classes) in schools,” she said.

        Before you run to the doctor for a Prozac prescription, keep this in mind: Weight loss associated with Prozac and a few other SSRI (selective serotonin reuptake inhibitor) antidepressants tends to be short-lived; the effect tapers off after a few months. And some antidepressants, including Paxil, cause weight gain.

        Experts agree that mood controlling medications like Topamax are only part of the solution for long-term weight loss. Lifestyle changes, including healthy eating and physical activity, and behavioral counseling also have to be included, as well as an understanding of how biochemistry affects weight and eating.

        “I really want to emphasize that all of these things are important,” Dr. Arrone said. “One of the exciting things that we're seeing in obesity research is the understanding that all of these things are important.”

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