Many Common Medications Can Add Unexpected Pounds

Sunday, May 16, 2004

By Michael Woods, Post-Gazette National Bureau

The pills millions of people take every day for diabetes, clinical depression, high blood pressure and other illnesses are small, weigh almost nothing and carry few calories.

Stacked up against a super-sized restaurant meal, a bucket of butter-laced popcorn or a jumbo cola, pills usually don't register with people worried about putting on pounds.

So it may seem hard to swallow, but certain prescription drugs can cause people to gain weight. Fast. Sometimes a pound a week.

Both doctors and patients overlook the possibility that weight gain can originate in the medicine chest, not just fast-food restaurants or couch-potato lifestyles, according to Dr. Lawrence J. Cheskin, director of the Weight Management Center at Johns Hopkins University in Baltimore.

"While obesity is being more widely recognized, I'm not sure the same can be said for patients' and physicians' recognition of the possible contributing role of prescription medicines," he said in an interview.

Cheskin and his associates first warned about the problem in 1990s, after noticing that a lot of patients who sought help at their weight management center were getting heavier when they started prescription drugs.

One 42-year-old woman, for instance, gained 42 pounds after taking lithium, a drug for mood swings. A 36-year-old supermarket worker gained 240 pounds while taking prednisone, a steroid.

"This is a really important subject," said Dr. Madelyn H. Fernstrom, director of the Weight Management Center at the University of Pittsburgh Medical Center.

Weight gain is among the side effects listed in official information sheets for some of the most frequently prescribed drugs in the United States. These include drugs taken by tens of millions of people for diabetes, depression, high blood pressure, gastric reflux and heartburn, and serious mental disorders.

Among them are top-selling medications such as the antidepressants Prozac, Zoloft, and Paxil; heartburn drugs such as Nexium and Prevacid; treatments for mental disorders such as Clozaril and Zypexa; diabetes drugs like Glucotrol, Diabeta, and Diabinese; and the high blood pressure drugs Minipress, Cardura, and Inderal. Some, like Inderal, are prescribed for several different health problems.

"Weight-gain drugs" is how Dr. George A. Bray, an obesity expert at Louisiana State University, describes such medications.

Fernstrom emphasized that although many drugs may list weight gain among potential side effects, relatively few are known to cause large or rapid increases in weight. "We have to be careful not to give the impression that all drugs cause weight gain," she said. "A few groups of medicines are associated with a lot of weight gain. Others really don't cause much."

Nobody knows exactly how many prescription drugs fall into those categories. Lists published in medical journals vary. One provided by Dr. George L. Blackburn, an obesity authority at Harvard University, includes more than 50 common drugs.

Internet drug discussion sites like the RxBoard (www.rxlist.com/rxboard.htm) carry accounts from patients who say they got fat after starting anti-cholesterol and other drugs not thought to cause much weight gain.

Nonprescription drugs also might cause weight gain. The antihistamine diphenhydramine, for instance, is on Blackburn's list. It is an ingredient in dozens of popular cold and allergy remedies, sleep aids and drugs to prevent motion sickness. An increasing number of prescription drugs, including some linked to weight gain, are also becoming available for sale without a prescription.

In some cases, it takes years for weight-gain to emerge as a troublesome side effect.

When the Prozac-Zoloft-Paxil family of popular antidepressants hit the market, doctors thought they caused weight loss. They were even prescribed for obese people trying to lose weight. Later, doctors realized that any weight loss is temporary, with the drugs often causing long-term weight gain.

Gaining weight can put people at risk for a variety of health problems, including Type 2 diabetes and heart disease. Unexpected weight gain also is a major reason patients stop taking some medicines, Fernstrom said, including drugs urgently needed to treat health problems far more dangerous than a few extra pounds.


But while studies show that "weight-gain" drugs can cause obesity in individual patients, researchers can't tell how much medicines contribute to the society-wide epidemic of obesity.

Bray has found that the number of obese people in the United States remained fairly steady -- about 20 percent of men and 15 percent of women -- until the mid-1970s. Then it took off; by 2000 the rates had risen 100 percent among men and 50 percent among women.

Use of prescription drugs rose during that period, and exploded in the 1990s. In 1993, the number of prescriptions written each year edged over the 2 billion mark for the first time. It reached 3 billion by 1999, and will top 4 billion by the end of 2004, according to the Association of Chain Drug Stores.

Almost every person in the United States now takes at least one prescription drug in a given year. Factor in people who take multiple drugs, and doctors write an average of 12 prescriptions annually for every person in the country.

Since average weight has been rising during the same period, weight-gain drugs have likely played a role in the obesity epidemic, although probably not as much as changes in diet, Bray said.

Consumers who would never suspect to look in the medicine chest for the cause of their weight gain have few sources of information.

Package inserts (which include the official description of a drug's side effects) usually give weight gain short shrift, including those for widely used weight-gain medicines like antidepressants.

About 19 million adults and 11 million children in the United States take drugs for clinical depression. Long-term use often causes weight gain.

The package insert for Paxil, an antidepressant linked to some of the biggest weight gains, gives the subject three words in a list of potential adverse effects -- "Frequent: Weight gain." There is no hint that one in four patients add at least 7 percent to their body weight. That's about nine pounds for a 130-pound person. Some report gains in the double digits.

Package inserts for the four other top-selling antidepressants -- Zoloft, Prozac, Celexa, and Luvox -- use the same approach, without detailing how much patients might gain.

Such side effects get similar treatment at online consumer-health sites, including the National Institutes of Health's popular "MedlinePlus" (www.medlineplus.gov). It lists weight gain as a "frequent" side effect for various drugs, without specifics.

Experts say doctors and patients are more aware that some drugs cause weight gain than others. It is a well known side effect of steroids like prednisone, older depression drugs like Elavil and Tofranil and a new family of antipsychotic drugs termed SGAs. Less recognition exists for other drugs, including the new family of antidepressants that includes drugs like Paxil and Zoloft.

"There is a general recognition among physicians that certain medications can promote weight gain," Fernstrom said. "But it is not often considered as a reason not to use a medication."

Nobody knows exactly why certain medicines make people gain weight. Patients who get heavier after starting a drug often say it makes them feel hungrier, or causes intense cravings for sweets or high-carbohydrate foods.

Drugs for depression and other mental conditions work by altering levels of brain chemicals, including those that make people feel hungry and full. Even a slight shift could produce big weight gains. An extra candy bar and soda each day, or one extra ice cream snack, could easily make a patient gain one pound a week, one study found.

On the other hand, poor appetite and weight loss are symptoms of some diseases, and weight gain can be a sign that the drug is working.

Weight gain and diabetes became such a serious problem in patients taking SGAs that several medical organizations issued a joint report early in 2004. It identified alternative medicines and detailed what doctors and patients can do to keep off the pounds.

SGAs are "second-generation antipsychotics," which became popular in the 1980s to treat serious mental conditions such as schizophrenia, bipolar disorder (or "manic depression" ), and psychotic depression. About 3 million people in the United States have schizophrenia and 2 million have bipolar disorder. Psychotic depression, which involves hallucinations, affects about two million of the 18 million people with depression.

Use of SGAs, however, has expanded to include other disorders, including aggressive behavior, post-traumatic stress syndrome and autism.

An expert panel convened by the American Diabetes Association, the American Psychiatric Association, the American Association of Clinical Endocrinologists and the North American Association for the Study of Obesity found that some SGAs cause rapid weight gain.The panel also found a documented link between SGAs and the development of prediabetes (a condition that involves abnormally high levels of sugar in the blood), diabetes, and elevated levels fats in the blood. Those are risk factors for heart attacks.

The panel also emphasized the benefits of anti-psychotic drugs, however.

"These medications have helped millions of people manage their symptoms," the report said. "For people who respond well, antipsychotics can mean the difference between leading an engaged, fulfilling community life and being severely disabled."

The panel recommended that doctors check each patient's body weight and risk for obesity, diabetes and high blood fats before prescribing a SGA and during treatment. It noted that some SGAs have a lower risk of weight-related side effects, and gave doctors information they need to pick low-risk drugs for patients with weight problems.

The SGA panel could be a model for gathering and spreading reliable information about other weight-gain drugs, according to some experts.

Dr. Lawrence Blonde, an authority on diabetes at the Oschner Clinic Foundation in New Orleans who also served on the SGA panel, said, patients and caregivers ought to be given additional information on the potential for weight gain.

Some of the existing information is from clinical trials that may exaggerate drug-related weight gain, he pointed out. In those experiments, patients were told not to make any changes in diet or lifestyle while taking the medicine.

"It may well be that patients could have avoided or reduced the weight gain if they had implemented appropriate nutritional and physical activity lifestyle changes," he said.

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Try blaming genes, not willpower
Is there biological basis for obesity? Our bodies want to hold on to fat
by VIRGINIA ANDERSON

DURHAM, N.C.—Biochemist Debbie Muoio's research into obesity is so complicated, she sounds as if she is speaking in scientific tongues as she describes her life's work.

Through it all, however, a simple theme emerges that many scientists believe could change the way we view and treat obesity:

Stop blaming yourself if you are overweight. Maybe your body made you do it.

"Obesity is not just a problem with people having no willpower," said Muoio, a Duke University nutritional biochemist. ``If you combine the wrong genes with the wrong environment ... you have big problems.''

While unpalatable to many, the view that the human body is often wired to hold on to fat has moved from farfetched to mainstream in the past 10 years.

Questions of how to treat obesity grow more urgent each year. So far, much of the public discussion on obesity has focused on whom or what to blame: fast food, TV and video games, or the obese themselves, for instance.

Then there are scientists, like Muoio, who have found a strong biological basis for obesity.

Researchers hope such findings lead to a change in treatment that draws on the expertise of nutritionists, psychotherapists and fitness trainers. The research could also lead to new treatments, such as drugs and individualized diet plans geared toward a person's unique biochemistry.

"Obesity may respond best to a team approach," said Dr. Howard Eisenson, director of the Duke Diet and Fitness Center. "We talk about obesity being an epidemic. If you compare it to cancer treatment, though, we're not treating it like it is an epidemic.''

In theory, one of the basic laws of thermodynamics should apply to weight loss: If a body takes in less fuel, or food, it should lose weight.

That's not always the case, though. Who doesn't know someone who can eat a gooey doughnut without gaining weight, and others who deprive themselves but never lose an ounce?

What makes some people gain weight, or not, is at the heart of research into the biology of obesity.

Some scientists subscribe to the theory of the so-called thrifty gene. They believe that some people may have more efficient fuel-burning metabolisms, allowing them to store fat more easily than others do.

Most human bodies are genetically programmed to hold on to fat, researchers believe. Stored fat keeps the body from starving and aids in reproduction by producing the hormone leptin.

Although food is plentiful now, the body still obeys those genes. When the eyes see food, they signal the brain, which signals the stomach. The stomach feels hungry because, on some level, the brain interprets that doughnut or burger as survival.

"We still have some evolutionary pieces of our brain still in place," said Martin Binks, health psychology director of the Duke Diet and Fitness Center. "When we see food, we feel hungry. And when can you go 15 minutes without seeing food cues?''

The stomach is also stuck in a biological time warp. In a holdover from the dawn of the species, when humans took a long time to eat, the stomach takes about 20 minutes before it signals the brain that it has had enough food.

On a much smaller scale, specialized cells, like muscle or liver cells, might play a role in weight gain. Muoio and other scientists believe by-products of fat metabolism might diminish the muscles' ability to respond to insulin, the hormone that tells cells when and how to use glucose, which provides energy. When insulin production is imbalanced, glucose remains in the blood, and that can lead to diabetes.

To test their theory, researchers manipulated the livers of rats to see if higher levels of an enzyme could make the rats burn more fat. It did.

"We were able to take animals on a high-fat diet and reverse their diabetes," Muoio said. "Through genetic manipulation, we made the liver burn a lot of fat.''

None of this research suggests that people should use biology as an excuse to eat poorly and remain inactive. But it might indicate that some may need more help to change their weight-gaining behaviours.

Researchers also stress that biology is only one part of the complicated obesity puzzle. Dr. Rena Wing, a director of the U.S. National Weight Control Registry and a professor of psychiatry and human behaviour at Brown University, said she "absolutely" believes in biological factors behind obesity. She is quick to note, however, that of the 4,000 people in the registry of successful weight losers, "75 per cent have a family history of obesity.''

One immediate benefit of the new research, scientists hope, will be a message of hope — that weight loss is achievable and that society will pull together, making changes to help people struggling desperately with obesity.

"You can't just exhort people to lose weight," said Richard Surwit, chief of medical psychology at Duke University Medical Centers. "We've tried that for 40, 50 years and it doesn't work.''

LINK

THE BIG FAT TRUTH ABOUT FAT

Faster Weight Loss?
Does the Atkins diet work better than the conventional low-fat route?
Studies so far: The longest study to date lasted only a year and was small—only 37 people completed the full 12 months, 20 of them on Atkins and the other 17 on a traditional low-fat regimen. The researchers found that those on the Atkins diet shed more pounds during the first six months, but by the end of the year there was no significant difference in the amount the two groups lost (about 13 pounds per person). Additional studies also showed faster results by those on Atkins-like diets, although much of the weight dropped in the first week or two is water.

But…there's nothing miraculous about eliminating carbs, says Dena Bravata, MD, a research scientist at Stanford University who did an analysis of low-carb diet studies. She maintains, like most experts, that losing weight is merely a matter of consuming fewer calories than you burn—and these diets help restrict calories. But one new pilot study from Harvard has just thrown a wrench into this accepted wisdom: When people on a low-fat regimen ate exactly the same number of calories as those on an Atkins-type diet, the latter group lost more weight. An additional low-carb group who ate 300 more calories per day still lost more than the low-fat dieters. Their study was very small (21 people) and lasted only 12 weeks, and the researchers can't explain the findings. But it opens the door to the heretical notion that not all calories are created equal. Stay tuned for further research.

Bad for Cholesterol?
For decades doctors have preached that eating too much saturated fat can lead to heart disease and obesity, and studies have consistently backed this up. So the biggest fear of many health professionals is that a diet of steak, eggs, and butter might increase the buildup of plaque in the arteries, which causes heart attacks and strokes. The limited number of short-term studies (the longest, a year) have not shown the Atkins diet to affect cholesterol adversely. But…again, the long-term effects are impossible to forecast. The authors of these studies and other experts in the field are quick to point out that any weight loss will cause a person's "bad" cholesterol levels to fall. They also caution that anyone trying this diet should reduce fat intake—especially saturated fat—once the maintenance phase begins; otherwise it's easy to regain what you lost and put yourself at increased risk of heart disease.

Dangerous for Kidneys and Bones?
Diets high in animal protein result in an acid overload that could lead to a higher risk of kidney stones and osteoporosis. Results of the only study to examine kidney function were striking. When subjects switched to Atkins from their regular diet, they excreted over 60 percent more calcium and their urine was markedly more acidic, placing them at higher risk of kidney stones. Shalini Reddy, MD, at University of Chicago, launched the study because, she says, "we had patients on the Atkins diet saying that they were getting kidney stones." However, during the eight-week study, Reddy and her colleagues could measure only risk factors, not actual kidney stones, which can take quite a while to form. As for osteoporosis, there are no long-term studies associating it with a low-carb diet. The NIH project will begin to address this concern.

Final Verdict
The Atkins diet seems to produce fast weight loss—perhaps even more effectively than low-fat regimens. But it gradually loses steam. More important, staying on this diet for longer than six months may pose serious health risks. Until science has the answers, you might try jump-starting your efforts with Atkins, but then ease into a lower-fat diet that's moderate on carbs, high in fiber, fruits, and vegetables, and proven safe over the long term.

from O magazine online March 2004

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