The Role of Appetite Suppressants in Postsurgical Patients

This month’s column by Robert Ziltzer, MD, FAAP

This column is dedicated to providing information on the medical management of obesity, which includes diet, exercise, behavioral change, and medication.

Column Editors: Craig Primack, MD, FAAP, Medical Bariatrician/Certified Medical Obesity Specialist/Co-Medical Director, Scottsdale Weight Loss Center PLLC, Scottsdale, Arizona; and Wendy Scinta, MD, MS, FAAFP, FASBP, Medical Director, Medical Weight Loss of NY, BOUNCE Program for Childhood Obesity, Manilus, New York; Clinical Assistant Professor of Family Medicine, Upstate Medical University, Syracuse, New York

When post-bariatric surgery patients fail to lose the expected amount of weight, or begin to regain weight, medical therapy can be a useful adjunct to band fills and an alternative to surgical revision. The compensatory decrease in leptin that occurs with weight loss leads to a lowering of the basal metabolic rate and an increase in hunger. While there is controversy regarding a “set point” of one’s weight, the tendency to regain is a continuing problem, especially after 3 to 5 years postoperatively. The decrease in leptin remains low for at least one year, and likely much longer. Leptin seems to be a signal that prevents starvation during times of calorie restriction.

The Role of Appetite Suppressants
Appetite suppressants can play a significant role when patients experience a slow down of weight loss or begin to regain lost weight. Sympathomimetic medications act to both decrease appetite and increase basal metabolic rate (BMR). The use of appetite suppressants, such as sympathomimetic medications, can offset the effects of the neuropeptides that tend to favor weight gain. Because there is no time at which the risk of regain resolves, long-term use of medications may be required.

Long-term use of appetite suppressants is becoming more widely accepted among obesity medicine specialists.
This column will briefly review the United States Food and Drug Administration (FDA)-approved weight loss medications available.

Phentermine
Phentermine is the most commonly used appetite suppressant. It is a sympathomimetic medication that increases metabolism and reduces hunger. Because it has a long half-life (21 hours), dosing before noon will reduce insomnia. Other common side effects include dry mouth, constipation, anxiety, and, less commonly, increased blood pressure and pulse rate. It should not be used in patients with tachyarrhythmia, and only with cardiology consultation in patients with stable coronary disease. While phentermine is FDA approved for use 12 weeks or less, the approval of phentermine/topiramate for long-term use suggests that phentermine can be used long term. The dosage range is 15 to 37.5mg daily.
A recent study[1] addressed the concerns of long-term use of phentermine. Patients who were abruptly discontinued from phentermine had no amphetamine-like withdrawal effects and no phentermine cravings.

Phentermine/Topiramate Controlled-Release
Phentermine/topiramate controlled-release (marketed under the brand name Qysmia [Vivus, Inc., Mountain View, California] is the first new appetite suppressant to reach the market in 13 years. The extended-release form of phentermine and topiramate acts centrally to decrease appetite and increase BMR. Patients’ one-year weight loss in the EQUIP study4 was 37 pounds at 56 weeks. Common side effects of Qysmia include dry mouth, paresthesias, constipation, insomnia, and change in taste, especially carbonated beverages. Serious side effects include birth defects and acute angle glaucoma. As a result, pregnancy tests need to be performed monthly in women of childbearing potential, and the medication immediately discontinued in the event of pregnancy. Qsymia is dosed daily, starting at 3.75mg (phentermine)/23mg (topiramate) daily for two weeks, then 7.5mg/46mg as tolerated. The maximum dose is 15mg/92mg.

Diethylpropion
Diethylpropion, also a sympathomimetic medication, has a shorter half life than phentermine and therefore can be used later in the day with less effect on sleep. It can be dosed 25mg three times daily. There is also a 75mg time-release tablet that is dosed once daily. Common side effects of diethylpropion include constipation, dry mouth, and restlessness. Increases in blood pressure and heart rate can occur.

Phendimetrazine
Phendimetrazine is a more potent sympathomimetic medication that reduces appetite and increases metabolism. Potential side effects include increased blood pressure and heart rate, as well as the more common side effects of restlessness, insomnia, and agitation. The potential for dependency is somewhat higher than the medications previously discussed. It is a schedule 3 prescription (while those mentioned above are schedule 4). It can be dosed as a long-acting 105mg form once daily or 35mg three times daily.

Orlistat is included in the list for completeness. It has no effect on appetite or metabolism, and acts on gastric and pancreatic lipases to reduce fat absorption. It is also available over the counter (Alli, GlaxoSmithKline, Parsippany, New Jersey). Weight loss is the most modest of the group. The malabsorptive effects may worsen vitamin deficiencies in patients who have undergone gastric bypass surgery. Side effects include diarrhea and bloating.

Conclusion
Appetite suppressants can be a useful adjunct to surgery in the long-term management of obesity. When patients fail to lose the expected amount of weight, or start regaining weight, assessing for uncontrolled hunger is essential. A thorough history and assessment of past medical history will direct the proper choice of appetite suppressants.

References
1.    Hendricks EJ. Greenway FL, Westman EC, Gupta AK. Blood pressure and heart rate effects, weight loss and maintenance during long-term phentermine pharmacotherapy for obesity. Obesity (Silver Spring). 2011;19(12):2351–2360.
2.    Hendricks EJ, Greenway FL. A study of abrupt phentermine cessation in patients in a weight management program. Am J Ther. 2011;18(4):292–299.
3.    Himpens J, Verbrugghe A, Cadiere GB, et al. Long-term results of laparoscopic Roux-en-Y Gastric bypass: evaluation after 9 years, Obes Surg. 2012;22(10):1586–1593.
4.    Allison DB, Gadde KM, Garvey WT, et al. Controlled-release phentermine/topiramate in severely obese adults: a randomized controlled trial (EQUIP). Obesity (Silver Spring). 2012;20(2):330–342.
5.    Ramón JM, Salvans S, Crous X, et al. J Gastrointest Surg. 2012;16(6):1116–1122.
6.    Gadde KM, Allison DB, Ryan DH, et al. Effects of low-dose, controlled-release, phentermine plus topiramate combination on weight and associated comorbidities in overweight and obese adults (CONQUER): a randomised, placebo-controlled, phase 3 trial. Lancet. 2011;377(9774):1341–1352.

Funding: No funding was provided for this article.
Financial disclosures: Dr. Ziltzer reports no conflicts of interest relevant to the content of this article.
author affiliation: Robert Ziltzer, MD, is Board Certified in Obesity Medicine, and the cofounder of Scottsdale Weight Loss Center in Arizona.  He is also Board Certified in Internal Medicine and Pediatrics. He is a marathon runner and cyclist.

Category: Medical Methods in Obesity Treatment, Past Articles