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(This article was first printed in the April 2006 issue of the Harvard Women’s Health Watch. For more information or to order, please go to Diet drugs have gotten a lot of press lately. In January 2006, a federal advisory panel recommended that the FDA make available, over the counter, a popular prescription weight-loss medication, orlistat (Xenical). The FDA usually takes the panel’s advice, but approval of the orlistat (which would be called Alli) is not a sure thing. Many question the drug’s effectiveness in a broader setting; others worry about its side effects. Considerable excitement surrounds rimonabant (Acomplia), a type of weight-loss drug that works by blocking the same receptors in the brain that cause the “munchies” in marijuana users. Rimonabant reduces weight, quiets food cravings, and improves cholesterol and other risk factors for heart disease, including waist circumference. We certainly need new weight-loss solutions. Two-thirds of adults in the United States are overweight or obese patient can cut down on portions and not feel like she’s starving. But unless she also understands how to eat less — by such strategies as learning to ignore environmental triggers to eat — she won’t benefit from taking an appetite suppressant. Drug therapy works better when it’s paired with an overall program of lifestyle change. A study published in the Nov. 17, 2005, New England Journal of Medicine found that after one year, Meridia-takers who participated in a comprehensive counseling program that promoted a low-calorie diet and 30-minute daily walks lost twice as much weight as subjects who received counseling alone or Meridia alone. The counseling component of the study involved 10 months of regular meetings led by mental health professionals who utilized the LEARN (Lifestyle, Exercise, Attitudes, Relationships, and Nutrition) program for weight management. Among its most important benefits, counseling can help establish realistic goals. The idea behind using weight-loss medications is to improve health and reduce disease risk, not to achieve an “ideal body weight.” A 5%–10% reduction in weight over time is one common goal. But even more modest weight loss can reduce these risks. Weight medications have a history of heart disease, Should not be taken by people with a history of heart disease, cardiac arrhythmia, stroke, or uncontrolled high blood pressure. Lipase inhibitor orlistat (Xenical) Cuts fat absorption in the intestine by 30%. Antidepressants bupropion (Wellbutrin), fluoxetine (Prozac) Wellbutrin increases levels of norepinephrine and serotonin; reduces food intake. Side effects include rapid heartbeat (phentermine), nervousness, restlessness, and diarrhea. The NIH guidelines make clear that weight-loss drugs be given only to people with a history of failure and safety concerns. In the 1950s and 1960s, dieters took amphetamines to quell their appetites and boost their metabolisms — until it was discovered that the pills were addictive and caused paranoia. The combination of fenfluramine and phentermine — popularly known as fen-phen — was widely used in the mid-1990s, until it and another drug, dexfenfluramine, were linked to heart valve disease and subsequently withdrawn from the market. (Phentermine alone is still used.) Until sibutramine was approved in 1997 for long-term use in obesity, the FDA had required that most such medications be prescribed for more than three months at a time. Blood pressure should be checked every four weeks. Serotonin/norepinephrine reuptake inhibitor sibutramine (Meridia) Increases levels of norepinephrine and serotonin; reduces food intake. Side effects include elevated blood pressure. Should not be taken by people with lower BMIs is likely to pose more risks than benefits. The NIH guidelines make clear that weight-loss drugs be given only to people with a body mass index (BMI) of 30 or more, or weight loss center — in the case of those with weight-related health problems — a BMI of 27 or more. The use of diet drugs by people with lower BMIs is likely to pose more risks than benefits. The NIH guidelines make clear that weight-loss drugs should be used only in combination with lifestyle modifications. There are several reasons for this. To lose weight requires recognizing and changing the behaviors that led to the weight gain. For example, many people gain weight because they’re in situations such as business travel that can trigger overeating and disrupt the body’s normal cues for hunger and satiety. And many people don’t expend enough calories because they don’t incorporate enough physical activity into their daily lives. Even more disconcerting: Weight loss can result in reduced calorie burning, whether the body is at rest or active. That’s why exercise is so important to weight-loss efforts: Increased muscle mass burns calories more efficiently. Another response to weight loss is ravenous hunger. A clinician may prescribe an appetite-suppressing drug so that an overweight or obese and at risk for several major medical conditions as well as for premature death. Even modest weight loss can reduce these risks. But as most of us know, losing weight can be extremely difficult, and keeping it off even more so. Most people who shed pounds regain them within five years. Little wonder that there’s intense interest in drugs to boost weight-loss efforts. But the reasons for weight problems are complex. Genetic makeup, hormones, brain chemistry, environmental influences, and psychosocial pressures all contribute. No pill can melt away fat or keep off the pounds. And the drugs being prescribed for weight loss don’t do the job by themselves. But for people whose health is at risk and who are struggling to reduce through diet and exercise, drug therapy may increase the odds of success. Experts agree that weight-loss drugs, which all have side effects, are not for the mildly overweight or those who just want to lose a few pounds to improve their appearance. Over the past few years, researchers have learned a lot about the biological causes of weight disorders. They’ve identified dozens of genes and begun to discover how these genes influence the many systems that affect weight. Weight-loss drugs can temporarily manipulate these systems. For example, sibutramine (Meridia) and phentermine (Adipex-P, others) suppress appetite, while orlistat reduces fat absorption. Some 100 new drugs are in the testing phase. Weight medications have a role to play in medical treatment, especially now that obesity is recognized as a metabolic disease and not a failure of desire or willpower, as was once thought. Clinicians are finding that obesity, like other chronic conditions, is often easier to manage with a judicious use of medications. Medication type/Name(s) Activity/Side effects/Comments Noradrenergic drugs phentermine (Adipex-P, Ionamin, others), diethylpropion (Tenuate, generic) Increase levels of norepinephrine; suppress appetite. Side effects include oily stool leakage, gas, bloating, and malabsorption of fat-soluble vitamins, especially A, D, E, and K. People taking orlistat should take supplements of these vitamins and be closely monitored for vitamin B12 and iron deficiencies. Antidepressants bupropion (Wellbutrin), fluoxetine (Prozac) Wellbutrin increases levels of norepinephrine and dopamine and helps control appetite. Side effects include dry mouth, agitation, constipation or diarrhea, headache, and insomnia. Prozac increases serotonin levels and may help suppress appetite. Side effects include insomnia, agitation, nausea, sleepiness, diarrhea or constipation, and problems with libido. Some people gain weight because they’re in situations such as business travel that can trigger overeating and disrupt the body’s normal cues for hunger and satiety. Balancing the demands of job and family can lead to a reliance on prepared foods, take-out, and restaurant meals, which are usually higher in calories than homemade meals. Others eat in response to stressful or emotionally challenging situations..
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