Prescription Medications for the Treatment of Obesity.

Obesity is a chronic disease that affects many people and often requires long-term treatment to promote and sustain weight loss. As in other chronic conditions, such as diabetes or high blood pressure, long-term use of prescription medications may be appropriate for some individuals. While most side effects of prescription medications for obesity are mild, serious complications have been reported. Valvular heart disease has recently been reported to occur in association with the use of certain appetite suppressant medications. As a result of these reports, the manufacturer has voluntarily withdrawn two medications, fenfluramine (Pondimin) and dexfenfluramine (Redux) from the market. There are few long-term studies evaluating the safety or effectiveness of other currently approved appetite suppressant medications. In particular, the safety and effectiveness of combining more than one appetite suppressant medication or combining appetite suppressant medications with other medications for the purpose of weight loss is unknown. Appetite suppressant medications should be used only by patients who are at increased medical risk because of their obesity and should not be used for "cosmetic" weight loss.

Medications That Promote Weight Loss

The medications most often used in the management of obesity are commonly known as "appetite suppressant" medications. Appetite commonly known as "appetite suppressant" medications. Appetite suppressant medications promote weight loss by decreasing appetite or increasing the feeling of being full. These medications decrease appetite by increasing serotonin or catecholamine--two brain chemicals that affect mood and appetite.

Most currently available appetite suppressant medications are approved by the U.S. Food and Drug Administration (FDA) for short-term use, meaning a few weeks or months. Sibutramine is the only appetite suppresant medication approved for longer-term use in significantly obese patients, although the safety and effectiveness have not been established for use beyond one year. (See table 1 for the generic and trade names of prescription appetite suppressant medications.) While the FDA regulates how a medication can be advertised or promoted by the manufacturer, these regulations do not restrict a doctor's ability to prescribe the medication for different conditions, in different doses, or for different lengths of time. The practice of prescribing medication for periods of time or for conditions not approved is known as "off-label" use. While such use often occurs in the treatment of many conditions, you should feel comfortable about asking your doctor if he or she is using a medication or combination of medications in a manner that is not approved by the FDA. The use of more than one appetite suppressant medication at a time (combined drug treatment) is an example of an off-label use. Using currently approved appetite suppressant medication for more than a short period of time (i.e., more than "a few weeks" is also considered off-label use.

Table 1

Prescription Appetite Suppressant Medications

Generic Name              Trade Name(s)
Dexfenfluramine           Redux (Withdrawn)
Diethylpropion            Tenuate, Tenuate dospan
Fenfluramine              Pondimin (Withdrawn)
Mazindol                  Sanorex, Mazanor
Phendimetrazine           Bontril, Plegine, Prelu-2, X-Trozine
Phentermine               Adipex-P, Fastin, Ionamin, Oby-trim
Sibutramine               Meridia

Single Drug Treatment

Several appetite suppressant medications are available to treat obesity. In general, these medications are modestly effective, leading to an average weight loss of 5 to 22 pounds above that expected with non-drug obesity treatments. People respond differently to appetite suppressant medications, and some people experience more weight loss than others. Some obese patients using medication lose more than 10 percent of their starting body weight--an amount of weight loss that may reduce risk factors for obesity-related diseases, such as high blood pressure or diabetes. Maximum weight loss usually occurs within 6 months of starting medication treatment. Weight then tends to level off or increase during the remainder of treatment. Studies suggest that if a patient does not lose at least 4 pounds over 4 weeks on a particular medication, then that medication is unlikely to help the patient achieve significant weight loss. Few studies have looked at how safe or effective these medications are when taken for more than 1 year.

Some antidepressant medications have been studied as appetite suppressant medications. While these medications are FDA approved for the treatment of depression, their use in weight loss is an "off-label" use. Studies of these medications generally have found that patients lost modest amounts of weight for up to 6 months. However, most studies have found that patients who lost weight while taking antidepressant medications tended to regain weight while they were still on the drug treatment.

NOTE: Amphetamines and closely-related compounds are not recommended for use in the treatment of obesity due to their potential for abuse and dependence.

Combined Drug Treatment

Combined drug treatment using fenfluramine and phentermine ("fen/phen") is no longer available due to the withdrawal of fenfluramine from the market. Little information is available about the safety or effectiveness of other drug combinations for weight loss, including fluoxetine/phentermine, phendimetrazine/phentermine, herbal combinations, or others. Until more information on their safety or effectiveness is available, using combinations of medications for weight loss is not recommended except as part of a research study.

Potential Benefits of Medication Treatment

Over the short term, weight loss in obese individuals may reduce a number of health risks. Studies looking at the effects of appetite suppressant medication treatment on obesity-related health risks have found that some agents lower blood pressure, blood cholesterol, triglycerides (fats) and decrease insulin resistance (the body's inability to use blood sugar) over the short term. However, long-term studies are needed to determine if weight loss from appetite suppressant medications can improve health.

Potential Risks and Areas of Concern When Considering Medication Treatment

When considering long-term appetite suppressant medication treatment for obesity, you should consider the following areas of concern and potential risks.

* Potential for Abuse or Dependence

Currently, all prescription medications to treat obesity are controlled substances, meaning doctors need to follow certain restrictions when prescribing appetite suppressant medications. Although abuse and dependence are not common with non-amphetamine appetite suppressant medications, doctors should be cautious when they prescribe these medications for patients with a history of alcohol or other drug abuse.

* Development of Tolerance

Most studies of appetite suppressant medications show that a patient's weight tends to level off after 4 to 6 months while still on medication treatment. While some patients and physicians may be concerned that this shows tolerance to the medications, the leveling off may mean that the medication has reached its limit of effectiveness. Based on the currently available studies, it is not clear if weight gain with continuing treatment is due to drug tolerance.

* Reluctance to View Obesity As a Chronic Disease

Obesity often is viewed as the result of a lack of willpower, weakness, or a lifestyle "choice"--the choice to overeat and underexercise. The belief that persons choose to be obese adds to the hesitation of health professionals and patients to accept the use of long-term appetite suppressant medication treatment to manage obesity. Obesity, however, is more appropriately considered a chronic disease than a lifestyle choice. Other chronic diseases, such as diabetes and high blood pressure, are managed by long-term drug treatment, even though these diseases also improve with changes in lifestyle, such as diet and exercise. Although this issue may concern physicians and patients, social views on obesity should not prevent patients from seeking medical treatment to prevent health risks that can cause serious illness and death. Appetite suppressant medications are not "magic bullets," or a one-shot fix. They cannot take the place of improving one's diet and becoming more physically active. The major role of medications appears to be to help a person stay on a diet and exercise plan to lose weight and keep it off.

* Side Effects

Because appetite suppressant medications are used to treat a condition that affects millions of people, many of whom are basically healthy, their potential for side effects is of great concern. Most side effects of these medications are mild and usually improve with continued treatment. Rarely, serious and even fatal outcomes have been reported. Two approved appetite suppressant medications that affect serotonin release and reuptake have been withdrawn from the market (fenfluramine, dexfenfluramine). Medications that affect catecholamine levels (such as phentermine, diethylpropion, and mazindol) may cause symptoms of sleeplessness, nervousness, and euphoria (feeling of well-being). Sibutramine acts on both the serotonin and catecholamine systems, but unlike fenfluramine and dexfenfluramine, sibutramine does not cause release of serotonin from cells. The primary known side-effects of concern with sibutramine are elevations in blood pressure and pulse, which are usually small, but which may be significant in some patients. People with poorly controlled high blood pressure, heart disease, irregular heart beat, or history of stroke should not take sibutramine, and all patients taking the medication should have their blood pressure monitored on a regular basis.

Primary pulmonary hypertension (PPH) is a rare but potentially fatal disorder that affects the blood vessels in the lungs and results in death within 4 years in 45 percent of its victims. Patients who use appetite suppressant medications for more than 3 months have a greater risk for developing this condition, estimated at 1 in 22,000 to 1 in 44,000 patients per year. While the risk of developing PPH is very small, physicians and patients should be aware of this possible complication when considering the risks and benefits of using appetite suppressant medications in the long-term treatment of obesity. Patients taking appetite suppressant medications should contact their doctors if they experience any symptoms such as shortness of breath, chest pain, faintness, or swelling in lower legs and ankles. It should be noted that the vast majority of cases of PPH have occurred in patients who were taking fenfluramine or dexfenfluramine, either alone or in combination. There have been only a few case reports of PPH in patients taking phentermine alone, although the possibility that phentermine alone may be associated with PPH cannot be ruled-out. No cases of PPH have been reported with sibutramine, but because of the low incidence of this disease in the underlying population, it is not know whether or not sibutramine may cause this disease.

Some animal studies have suggested that appetite suppressant medications affecting the serotonin system, such as fenfluramine and dexfenfluramine, can lead to damage to the central nervous system. Damage to the central nervous system has not been reported in humans. Some patients have reported depression or memory loss when using some appetite suppressant medications or combinations of medications, but it is not known if these problems are caused by the medication or by other factors.

In July, 1997, researchers at the Mayo Clinic reported a case series of 24 women who developed an unusual form of disease of the heart valves. All 24 women were using the combination of fenfluramine and phentermine. The disease primarily affected the left side of the heart, and five patients required valve replacement. In cases where samples of valve tissue were obtained, there was an unusual appearance of the heart valves generally only seen with a serotonin-producing tumor called carcinoid or with excessive amounts of medications containing ergot. Following these initial case reports, the Food and Drug Administration (FDA) has continued to receive a number of reports of similar valve disease from physicians. Some of these cases involved patients who were taking fenfluramine or dexfenfluramine alone. No cases were reported in patients taking phentermine alone. In addition, physicians at five sites provided information to the FDA regarding patients, most of whom did not have signs or symptoms of valve disease. About 30% of patients at these sites showed some evidence of damaged valves, usually mild or moderate. While this was not a controlled study, and further studies are needed to determine how common the problem is in treated patients compared to the general population of overweight people, the findings were of enough concern to prompt the FDA to ask the manufacturers of fenfluramine and dexfenfluramine to voluntarily recall the drugs. This withdrawal took place on September 15th 1997. Patients who were on fenfluramine or dexfenfluramine have been advised to discontinue the drug, and to contact their physicians for an evaluation to look for signs and symptoms of heart disease and to determine the need for an echocardiogram. For more information about the withdrawal of fenfluramine and dexfenfluramine, you can access the FDA website on Questions and Answers about Withdrawal of Fenfluramine (Pondimin) and Dexfenfluramine (Redux) at http://www.fda .gov/cder/news/fenphenqa2.htm. Two small studies looking at relationships between sibutramine and valvular heart disease did not find any increase in valve lesions in patients taking sibutramine compared with placebo.

Commonly Asked Questions About Appetite Suppressant Medication Treatment

Q: Can medications replace physical activity or changes in eating habits as a way to lose weight?

A: No. The use of appetite suppressant medications to treat obesity should be combined with physical activity and improved diet to lose and maintain weight successfully over the long term.

Q: Will I regain some weight after I stop taking appetite suppressant medications?

A: Probably. Most studies show that the majority of patients who stop taking appetite suppressant medications regain the weight they had lost. Maintaining healthy eating and physical activity habits will increase your likelihood of keeping weight off.

Q: How long will I need to take appetite suppressant medications to treat obesity?

A: The answer depends upon whether the medication helps you to lose and maintain weight and whether you have any side effects. Because obesity is a chronic disease, any treatment, whether drug or nondrug, may need to be continued for years, and perhaps a lifetime, to improve health and maintain a healthy weight. There is little information on how safe and effective appetite suppressant medications are for more than 1 year of use.

Q: What dosage of appetite suppressant medication would be right for me?

A: There is no one correct dose for appetite suppressant medications. Your doctor will decide what works best for you based on his or her evaluation of your medical condition and response to treatment.

Q: I only need to lose 10 pounds. Are appetite suppressant medications appropriate for me?

A: Appetite suppressant medications may be appropriate for carefully selected patients who are at significant medical risk because of their obesity. They are not recommended for use by people who are only mildly overweight unless they have health problems that are made worse by their weight. These medications should not be used only to improve appearance.

What to Discuss with Your Doctor Before Choosing Appetite Suppressant Medication Treatment

Before choosing appetite suppressant medication treatment for the long-term management of obesity, you should talk to your doctor about any concerns you may have. In addition, it is important that you discuss the following issues with your doctor.

How will I be evaluated to determine if l am an appropriate candidate for appetite suppressant medication treatment?

Your physician will look at a number of factors to determine if you are a good candidate for prescription appetite suppressant medication treatment of obesity. He or she will determine how overweight you are and where your body fat is distributed (see WlN's fact sheet Understanding Adult Obesity for further information). Your doctor may do the following:

* Take a careful medical history and perform a physical examination.

* Look at your personal weight history.

* Ask whether you have relatives with illnesses related to overweight, such as noninsulin-dependent diabetes mellitus (NIDDM) or heart disease.

* Discuss the methods you have used to lose weight in the past.

* Evaluate your risk for obesity-related health problems by measuring your blood pressure and doing blood tests.

If your doctor determines that you have obesity-related health problems or are at high risk for such problems, and if you have been unable to lose weight or maintain weight loss with nondrug treatment, he or she may recommend that you use prescription appetite suppressant medications. Appetite suppressant medications may be appropriate for carefully selected patients who are at significant medical risk because of their obesity. They are not recommended for people who are only mildly overweight unless they have health problems that are made worse by their weight. These medications should not be used only to improve appearance.

What other medical conditions or medications might influence my decision to take an appetite suppressant medication ?

It is important that you notify your physician if you have any of the following medical conditions:

* Pregnancy or breast-feeding

* History of drug or alcohol abuse

* History of an eating disorder

* History of depression or manic depressive disorder

* Use of monoamine oxidase (MAO) inhibitors or antidepressant medications

* Migraine headaches requiring medication

* Glaucoma

* Diabetes

* Heart disease or heart condition, such as an irregular heart beat

* High blood pressure

* Planning on surgery that requires general anesthesia

What type of program will be provided along with the medication to help me improve my eating and physical activity habits?

Studies show that appetite suppressant medications work best when combined with a weight-management program that helps you improve your eating and physical activity habits. Ask your doctor any questions or concerns that you may have about good nutrition and physical activity.

Appropriate Treatment Goals for Using Prescription Appetite Suppressant Medications

If you and your doctor believe that the use of appetite suppressant medications may be helpful for you, it is important to discuss the goals of treatment. Improving your health and reducing your risk for disease should be the primary goals. For most severely obese people, achieving an "ideal body weight" is both unrealistic and unnecessary to improve their health and reduce their risk for disease. Most patients should not expect to reach an ideal body weight using the currently available medications. Even a modest weight loss of 5 to 10 percent of your starting body weight can improve your health and reduce your risk factors for disease. Use of appetite suppressant medications for cosmetic purposes is not appropriate.

Appetite suppressant medications should be used with a program of behavioral treatment and nutritional counseling, designed to help you make long-term changes in your diet and physical activity. You should see your physician regularly so that he or she can monitor how you are responding to the medication, not only in terms of weight loss, but how it effects your overall health. Again, if you experience any serious symptoms, such as chest pains or shortness of breath, contact your doctor immediately.

Long-term use of prescription appetite suppressant medications may be helpful for carefully selected individuals, but little information is available on the safety and effectiveness of these medications when used for more than 1 year. By evaluating your risk of experiencing obesity-related health problems, you and your physician can make an informed choice as to whether medication can be a useful part of your weight-management program.

End note: This e-text is a modified version of a review article on the long-term use of appetite suppressant medications to manage obesity, appearing in a 1996 issue of the Journal of the American Medical Association. Both the review article and this fact sheet were developed with the advice of the National Task Force on Prevention and Treatment of Obesity, a working group of leading obesity and nutrition researchers from across the country. This e-text was revised in October, 1997, in response to additional information reported regarding an association between valvular heart disease and certain appetite suppressant medications, and in February, 1998 in response to the approval of sibutramine.

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The Weight-control Information Network (WIN) is a service of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), part of the National Institutes of Health, under the U.S. Public Health Service. Authorized by Congress (Public Law 103-43), WIN assembles and disseminates to health professionals and the public information on weight control, obesity, and nutritional disorders. WIN responds to requests for information; develops, reviews, and distributes publications; and develops communications strategies to encourage individuals to achieve and maintain a healthy weight.

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NIH Publication No. 97-4191 December 1996

e-text last updated: 16 March 1998