Some Antipsychotics, Antidepressants Are Weight Gain in a Pill

Some antipsychotics, antidepressants and other prescription drugs can lead patients to pack on pounds

The pills millions of people take every day for diabetes, clinical depression, psychotic disorders, high blood pressure, and other illnesses are small, weigh almost nothing, and aren't packed with calories.

Stacked up against a super-sized restaurant meal, a bucket of butter-laced popcorn, or a jumbo cola, pills usually don't raise red flags when people worry about putting on pounds.

Although it may seem hard to swallow, certain prescription drugs can cause people to gain weight - sometimes a pound a week - they get little attention when experts search for causes of the national epidemic of obesity.

Both doctors and patients overlook the possibility that weight gain can originate in the medicine chest, as well as fast food restaurants and couch-potato lifestyles, according to Dr. Lawrence J. Cheskin. He directs 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.

Dr. Cheskin and his associates first warned about the problem in a medical report published in the 1990s. They realized that many patients seeking help for obesity at the center gained large amounts of weight after starting antipsychotics, antidepressants and other 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 drug.

"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 side effects listed in official information sheets for some of the most frequently prescribed drugs in the United States. They include drugs taken by tens of millions of people for diabetes, clinical depression, high blood pressure, gastric reflux and heartburn, and serious mental disorders like schizophrenia and bipolar disorder.

Among them are top-selling medications like the antidepressants Prozac (Fluoxetine), and Paxil (Paroxetine); heartburn drugs such as Nexium and Prevacid; Clozaril and Zypexa, used to treat serious mental disorders; 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, described such medications.

Dr. Fernstrom emphasized that although many prescription drugs may list weight gain among the potential side effects, relatively few are known to cause large weight gains. "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 from one to another. One provided by Dr. George L. Blackburn, an obesity authority at Harvard University, includes more than 50 common drugs.

Internet drug discussion sites carry accounts from patients who say they got fat after starting anti-cholesterol and other drugs not thought to cause heavy weight gain.

Nonprescription may also cause weight gain. The antihistamine, diphenhydramine, for instance, is on Dr. 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, also become available for sale without a prescription.

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

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

Weight gain is bad because it puts people at risk for a variety of health problems, including Type 2 diabetes and heart disease. Unexpected weight gain also ranks among the main reasons why patients stop taking some medicines, Dr. Fernstrom noted, including those urgently needed to treat health problems far more dangerous than extra pounds.

Studies show that weight-gain drugs can cause obesity in individual patients. However, researchers can't tell how much medicines contribute to the society-wide epidemic of overweight and obesity.

Dr. Bray has studied why obesity skyrocketed in the United States between 1970 and the 1990s. The number of obese people remained fairly steady - about 20 percent of men and 15 percent of women - until the mid-1970s. Then it took off on an upward spiral that by 2000 meant a 100 percent increase in obesity in men and a 50 percent rise in 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 2001, 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 a year. Factor in people who take multiple drugs, and doctors write an average of 12 prescriptions annually for every person in the country.

"For some, weight gain drugs may play a role," Dr. Bray said. But he thinks that dietary changes probably had a bigger role in the obesity epidemic.

New ways of using drugs also are contributing to patients' weight gain.

Doctors have known for decades, for instance, that insulin makes some diabetes patients gain weight. About 1 million people with Type 1 diabetics take insulin injections, as do some of the 15 million with Type 2 diabetes.

Until the 1990s, patients almost always took just one insulin shot a day. Then, however, a landmark clinical trial showed that "intensive insulin therapy" -- multiple injections each day -- did a better job of controlling the disease's complications. Those include a high risk of heart attacks, vision loss, and other serious health problems.

Patients on intensive therapy, however, gain an average of 10.5 pounds more than those taking one insulin shot daily, according to a major 2001 study.

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 of certain antidepressants often causes weight gain.

Consider, however, the package insert for Paxil (Paroxetine), an antidepressant linked to some of the biggest weight gains. Weight gain gets 3 words, which appear in a listing of Paxil's (Paroxetine) adverse effects. "Frequent: Weight gain." There is no hint that about 1 in 4 patients add at least 7 percent to their body weight. That's about 9 pounds for a 130-pound person. Some report much larger gains in the double-digit range.

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

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

Experts say that doctors and patients are aware of those side effects for certain drugs, especially those to treat serious psychiatric illnesses.

"Increased weight gain is a potential side effect of a number of different classes of medications," said Dr. Neal D. Ryan, a professor of psychiatry at the University of Pittsburgh Medical Center. "Because many patients and many physicians are careful about their weight, this side effect is probably less likely to be overlooked than others."

Dr. Fernstrom said there's major recognition for steroids like prednisone; older clinical depression drugs like Elavil and Tofranil; and a new family of antipsychotic drugs termed the 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," she said. "But it is not often considered as a reason not to use a medication."

Nobody, however, knows exactly why certain medicines make people gain weight. Patients who gain weight on such drugs often say they feel hungrier, or develop intense cravings for sweets or high-carbohydrate foods.

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

Poor appetite and weight loss are symptoms of some diseases, and weight gain also may be a sign that the drug is working.

Weight gain and diabetes became such a serious problem in patients taking atypical antipsychotics (SGAs) that several medical organizations issued a joint report early in 2004. It identified drugs that cause weight gain and 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 like 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 2 million of the 18 million people with depression.

Use of the drugs, however, has expanded to include other disorders, including aggressive behavior, posttraumatic stress syndrome, and autism.

The American Diabetes Association, the American Psychiatric Association, the American Association of Clinical Endocrinologists, and the North American Association for the Study of Obesity convened an expert panel to study the side effects.

It concluded that some SGAs do cause rapid weight gain, with many patients putting on a pound a week - mostly fat -- after treatment starts. Weight gain may continue even after a year of treatment.

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 of fats in the blood. Those are risk factors for heart attacks.

However, the panel also emphasized the benefits of antipsychotic drugs.

"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 on 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.

"I think it would be a good idea to develop an expert panel to review weight gain from specific drugs," said Dr. Samuel Klein. He is an authority on obesity at Washington University in St. Louis who served on the SGA panel.

"Once such a panel reaches some conclusions, a decision could be made on whether the information is important enough to include in package inserts or patient information sheets."

Dr. Lawrence Blonde said studies should provide specific information on the whole topic of prescription medication and weight gain. An authority on diabetes at the Oschner Clinic Foundation in New Orleans, he also served on the SGA panel.

He cited a need for information on the drugs most likely to cause weight gain, the percentage of patients who gain weight, how much weight gain is likely to occur, and how long it will last.

"I think it would be useful to provide patients and caregivers with some additional information on potential weight gain from prescription drugs," he noted.

Some of the existing information is from clinical trials that may exaggerate the seriousness of 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.

There are hints that patients can lose the weight with changes in lifestyle, switching to alternative medicines that don't cause weight gain, or adding new medicines to control appetite.

A 2003 study at Dartmouth Medical School, for instance, focused on patients who gained an average of 65 pounds while taking SGAs. Lifestyle and medication changes enabled them to shed about two-thirds of the weight.

"Physicians and their patients need to choose drugs after assessing both the risks and the benefits that a particular medication might have for the condition. Depending on the clinical situation, the benefits of taking a medication may exceed the risks of weight gain.

"Before prescribing such a drug, the physician should discuss the potential risks of weight gain, and attempt to minimize it by recommending appropriate lifestyle changes," Dr. Blonde added.

"But it shouldn't be given in isolation. Patients should understand that the benefits of taking the medication may far exceed the risks of weight gain. For patients who already are overweight, there may be alternative medicines that do not seem to be associated with weight gain."

Dr. Fernstrom cautioned that patients who gain weight while taking a medication should not stop. Rather, she suggested that they talk with the doctor. Changes in lifestyle, rather than the drug, may be the real cause. In addition, there may be an alternative medicine not linked to weight gain.

Likewise, possible weight gain should not discourage patients from taking needed drugs.

"Raise the issue with your doctor," Dr. Fernstrom added. "Say that you are concerned about weight gain as a side effect and ask if there are other medications available. If the drug of choice is the only option, and you do notice weight gain, you can make some lifestyle changes."

That means steps like getting more exercise, reducing food intake, and drinking only non-calorie beverages. Even 30 minutes of walking can burn about 150 calories, she noted.