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Pharmacotherapy and Surgical Treatment for Obesity
A variety of drugs are available to treat obesity, said Renee Ahrens Thomas, PharmD, MBA, Associate Professor of Pharmacy Practice at Shenandoah University, Winchester, Virginia.
However, medications should always be used as an adjunct to diet and exercise, and they are only indicated for individuals with a BMI above 30, or above 27 with any risk factor, and if diet and exercise are ineffective for 3 months.
The first class of drugs are the amphetamine-like anorexiants, which act by increasing norepinephrine in the brain to suppress the appetite; these include diethylpropion, phendimetrazine, phentermine, and benzphetamine. Although this class is effective at reducing weight by 3 kg or more in 6 months, they can only be used on a short-term basis as tolerance quickly develops. They also are associated with many adverse effects, drug interactions, and contraindications that are typical of amphetamines. In addition, there is a high potential for abuse of these drugs.
Sibutramine represents another class of centrally acting anti-obesity drugs that works by inhibiting the reuptake of norepinephrine, serotonin, and dopamine. In contrast to the effects of the anorexiants, the initial weight loss is achieved only slowly; although the average weight loss is 4.5 kg at 1 year, weight is typically regained when the drug is discontinued. In addition, it is associated with cardiovascular adverse effects and contraindications. But, if this monoamine reuptake inhibitor is effective, could other drugs such as antidepressants work as well? In examining fluoxetine, both weight losses and gains were seen, while bupropion resulted in some short-term weight loss. In a recent meta-analysis of anti-obesity drug trials, these 2 drugs caused mean weight losses of 3.15 kg at 12 months and 2.8 kg at 6-12 months, respectively.
Finally, the other major drug approved for weight loss is the locally acting orlistat, which inhibits fat-digesting lipases in the gastrointestinal (GI) tract. Orlistat's well-known adverse effects include soft, liquid, or oily stools, flatulence, and fecal urgency or incontinence. Including up to 6 grams of fiber with each dose can reduce many of these effects. However, the absorption of fat-soluble vitamins is inhibited, and orlistat's concomitant use with cyclosporine can reduce the latter's absorption by 50%, so their administration should be spaced at least 2 hours apart. A US Food and Drug Administration (FDA) advisory panel has just endorsed orlistat for over-the-counter (OTC) sales. Orlistat would be the recommended medication for patients who derives a majority of their calories from fat, whereas sibutramine would be better for patients who have trouble controlling portion size or between-meal snacks.
Among newer therapies on the horizon, topiramate has shown some efficacy when combined with diet, exercise, and behavior modification. Rimonabant, a cannabinoid antagonist, is perhaps the most novel approach to obesity therapy, derived from the well-known effects of cannabinoids to enhance appetite. The recently published RIO-North America trial demonstrated a mean weight loss of 6.3 kg over 1 year, as well as a reduction in waist circumference, serum triglycerides, and an increase in serum HDL. However, the significance of this trial has been called into question because of the large number of participants lost to follow-up. Adverse effects reported for rimonabant include nausea and depressive symptoms.
There are a multitude of OTC or herbal medications that span the spectrum of proven efficacy, many of which fall into 1 of 3 categories: serotonin-related agents, thermogenic agents, and digestion inhibitors. From the first group, St. John's wort has not been shown to be effective, and while serotonin itself (5-hydroxytryptophan, 5-HT) hastens satiety and may induce weight loss, it is also associated with eosinophilia myalgia syndrome and should not be recommended.
The thermogenic agents consist of the herb ephedra (ma huang) and its active ingredient ephedrine, which increases norepinephrine release, much like the amphetamines. Preparations of this type often include caffeine, most notably Zantrex-3, which has more than 1 gram of caffeine, equivalent to the caffeine content of more than 30 cans of cola. Ephedra has been banned in the United States since 2004 due to its cardiovascular and psychiatric adverse effects, dangers that are increased with added caffeine. The US FDA has maintained that ban even though a federal judge declared it unlawful in 2005.
Substances that are thought to prevent fat absorption include fiber (eg, psyllium), which has no known efficacy, and glucomannan, a fibrous polysaccharide that has not yet been convincingly shown to work. Others with no proven efficacy are chitosan, from shellfish exoskeleton, and guggul, the resin of a tree native to India. Various other supplements have been promoted as weight-loss agents even though there is little or no evidence to support those claims: conjugated linoleic acid, 7-keto-dihydroepiandrosterone (7-keto-DHEA, a testosterone precursor), garcinia, chromium, and pyruvate. Large doses of the latter can substitute for carbohydrates and may be effective, but such large quantities are required that cost and side effects become an issue.
In conclusion, of all the OTC supplements and herbal preparations, only ephedrine and 5-HT have been proven effective, and both of these may be unsafe. One other preparation worth noting is the so-called Brazilian diet pills (eg, Emagrece, Brazilian Slim Complex, Herbathin), which contain a potpourri of agents such as amphetamines and fluoxetine but are frequently mislabeled and adulterated. Patients should be strongly advised to avoid these.
Finally, Dr. Thomas summarized some nutritional issues around bariatric surgery, focusing on bypass surgeries. Due to the drastically reduced absorption area of the GI tract after this procedure, many nutritional deficiencies can arise. Poor absorption of calcium, iron, vitamin B12, folate, and proteins can contribute to postsurgical complications such as wound infection or bleeding, and may result in osteoporosis, cholecystitis, gastroesophageal reflux, general malnutrition, and many other problems. Patients should be directed to supplement calcium in its citrate form with added vitamin D, as found in Citracal (Mission Pharmaceuticals) rather than Tums (GlaxoSmithKline), as well as consuming children's chewable multivitamins and perhaps additional iron.
The effect of bariatric surgery on the absorption of medications has not been extensively examined, but the hypochloric environment of the gastric bypass will reduce solubility of many compounds, which can be circumvented by using liquid forms whenever possible. Slow-release products should be avoided and enteric-coated tablets used with caution.