Editor's note: This article was originally published in The Tribune on Nov. 18, 2007.
Adrien Nicholson doesn't need a medical expert to tell her how difficult it is to lose weight or that most people fail no matter how hard they try.
The 51-year-old San Luis Obispo resident said she believes she has tried every diet invented: the grapefruit diet, the cabbage soup diet, Weight Watchers, over-the-counter pills, and on and on, to no avail.
Three years ago, though, she began taking a weight-loss formula prescribed by Dr. Thomas Najarian of Los Osos.
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Since then, she has lost more than 200 pounds.
The combination of topiramate, an antiseizure drug, and phentermine, an appetite suppressant, curtails Nicholson's appetite. When combined with a daily 800-calorie diet and mild exercise, she sheds 1 to 2 pounds a week.
Given that two-thirds of Americans are either overweight or obese, according to the U.S. Centers for Disease Control and Prevention, finding effective and safe weight-loss drugs is a top priority in health care and a potential gold mine for pharmaceutical companies.
Some medical experts, however, caution that the history of weight-loss drugs has been fraught with challenges, including sometimes dangerous side effects, and that prescribing drugs for weight loss before they are approved for that purpose could be unsafe.
"Every obesity therapy that has been thought up so far has a downside, " said Robert Lustig, a professor of pediatric endocrinology at UC San Francisco.
But as Nicholson knows, the downsides of obesity are also tremendous. She balanced the potential risks of the drug combination with the definite risks of being 300 pounds overweight and chose the pills.
Promising, but too soon?
Najarian, an internist for 30 years, is a Boston native. He opened the Najarian Center in Los Osos in 2001 and has since treated thousands of local residents for obesity with his combination therapy, known commercially as Qnexa.
Najarian invented and patented Qnexa, which incorporates the active ingredients of topiramate and phentermine. Vivus Inc., a Silicon Valley pharmaceutical company, is developing the drug with Najarian's help.
Qnexa recently entered the final leg of clinical trials required for approval by the U.S. Food and Drug Administration. If the results from the yearlong, 4,500-person controlled study are successful and don't show risks of serious side effects, the drug could enter the market in 2010, Najarian said.
Because the drug combination is not yet FDA-approved as a treatment for obesity, it is known as an off-label treatment. Off-label use occurs often in the treatment of many conditions, but it remains controversial.
Lustig said he does not widely prescribe off-label treatments for obesity and would not prescribe a treatment he had financial ties to.
"There's a huge ethical issue here, " he said.
Najarian said he fully discloses to patients that while these medications are FDA-approved, they are not approved in this combination for weight loss. He also discloses his financial stake in the drug's development.
Medical studies support the safety of his treatment, he said. A preliminary placebo-controlled study on 200 people at Duke University Medical Center, which included cardiovascular checkups, showed the drug was well-tolerated and helped people lose an average of 20 pounds in 24 weeks.
Dr. Richard Atkinson, president and co-founder of the American Obesity Association, said he has used the topiramatephetermine combination on patients and believes its greatest advantage is that patients using it do not seem to reach a plateau in their weight loss.
"It's probably going to be the most successful thing in terms of weight loss since fen-phen, " Atkinson said.
Many people remember the fen-phen phenomenon in the 1990s, which helped up to 18 million people lose weight until it was linked to potentially fatal heart valve problems and pulled from the market.
Najarian said his combination uses a mechanism different from fen-phen, so the heart valve deterioration should not be an issue. He does not expect to see dangerous side effects from Qnexa because the topiramate doses are far lower than what was approved to treat epilepsy years ago.
He acknowledged this remains unproven until results of the large, long-term clinical trial are available, most likely in 2009.
Side effects of topiramate include dizziness, fatigue and loss of cognitive capabilities. Phentermine's side effects include tingling in the hands and feet, high blood pressure, nervousness and anxiety.
Templeton resident Rebecca Sprain, 58, said she stopped the treatment because the phentermine made her feel anxious and hyper. But first, she lost 75 pounds.
Sprain has a heart problem and said Najarian worked closely with her regular doctors to monitor her health while she was on the program.
"My cardiologist told me I was a time bomb with my weight problem anyway, " Sprain said.
Joseph Bettencourt, a Templeton family practice doctor, said Najarian's program has benefited many patients.
"I think he is extremely well-informed, " Bettencourt said. "He has caused more significant sustained weight loss than any other program or doctor I've seen."
'This isn't a magic pill'
Najarian belongs to the growing school of health experts who consider obesity a chronic disease, like diabetes and high blood pressure. They say the evidence shows that obesity is more than a "willpower" issue and involves complicated physiological changes that can best be treated with medications.
Gastric bypass surgery is currently the most successful treatment for obesity in terms of overall weight lost, but it is extremely costly, invasive and not always successful. Experts say treating obesity with medication could save money and reduce risks.
Any successful treatment with medications will likely be a lifelong regimen of drug combinations that tackle various causes of obesity, experts say.
"There's not going to be one treatment that works for everybody, " Lustig said.
The FDA approves weight-loss medications only for obese people with a body mass index of 30 or higher (for example, someone who is 5 feet 6 inches and weighs 190 pounds) or people with a BMI of 27 or higher and other risk factors, such as hypertension. BMI is found by dividing weight in kilograms by height in meters squared.
These drugs are not for people who want to lose a few extra pounds. To maintain their weight loss, most people will have to take them their entire lives; if they stop, the weight will likely return.
"This is not a short-term thing, " Najarian said.
The drug therapy also requires lifestyle changes, including a high-protein, low-calorie diet, exercise and stress management.
"This isn't a magic pill, " Najarian said. "It works better if a person wants to lose weight and is motivated to exercise and eat well."
Nicholson can attest to that. She goes to the gym on her lunch hour and avoids all sugar. She eats lots of vegetables and protein. A typical day's menu might be a hard-boiled egg for breakfast, a can of soup and piece of fruit for lunch, and a chicken breast and salad for dinner.
"The pills help, " she said. "Believe me, they do help. But you have to want it. You have to resolve yourself to a new lifestyle."