March 2009
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Beyond Diet and Exercise
This is the first part of an evidence-based review of nontraditional therapies for childhood and adolescent obesity.
By Sarah C. Armstrong, MD; Richard Chung, MD; Alexandra C. Russell, MSc; Michelle Bailey, MD; and Terrill Bravender, MD, MPH
This portion of the review covers pharmacotherapy, bariatric surgery, and literacy-based approaches.
As the epidemic of childhood obesity continues to escalate, both traditional and nontraditional solutions have been attempted. Most widely described are the so-called big two: diet and exercise. Many other options exist for treatment of overweight children and their families. This review describes existing evidence for nonlifestyle treatment including pharmacotherapy, bariatric surgery, literacy-based and technology-based interventions, and therapies that integrate complementary medicine approaches.
Pharmacotherapy (SC Armstrong)
The use of pharmacotherapy to achieve weight loss in the pediatric population presents complex management issues. No long-term studies of safety or efficacy for pharmacologic treatment of obesity in children currently exist. Few clinical trials have evaluated outcomes at 6 months and none beyond 12 months.1 In adults, weight-loss medications produce an average weight loss of 5% to 10%, an effect that plateaus at 4 to 6 months, with weight regain when medications are discontinued.2-4 Risks are associated with the use of these medications in adults, and there are potential risks in children and adolescents as well. The US Food and Drug Administration (FDA) withdrew fenfluramine, ephedra, and phenylpropanolamine from the market due to cardiovascular side effects.5 Even with medications deemed safe for adults, their effects on growth and development in children remain unknown.
Despite these limitations, certain high-risk groups of obese children may be candidates for pharmacotherapy as an adjunct to lifestyle modification. Indications include a body mass index (BMI) >99th percentile with significant comorbidities.6 Six medications are currently licensed in the United States for weight loss in adults, however, only two are approved for use in children.
Sibutramine (Meridia, Abbott) suppresses appetite centrally through nonselective reuptake inhibition, primarily involving serotonin, norepinephrine, and to a lesser degree, dopamine pathways. The recommended starting dose is 10 mg once a day, increasing to 15 mg daily if blood pressure and pulse rate are stable and no weight loss is achieved at 4 weeks. The 5-mg dose is reserved for those who do not tolerate the 10-mg dose. Maximum effect in clinical trials was observed at a dose of 10 to 20 mg per day, but doses >15 mg a day are not recommended because of the likelihood of hypertension.7 Sibutramine is FDA approved for use in children aged >16 years, for a maximum of 2 years. Side effects include tachycardia and hypertension due to vasoconstriction.
To date, three studies have evaluated the efficacy and safety of sibutramine in adolescents.8-10 The largest, a 1-year randomized trial of 498 adolescents, found that patients who received sibutramine plus lifestyle modification lost an average of 6.35 kg, compared with a weight gain of 1.8 kg in the placebo group at 1 year. The effects plateaued after approximately 6 months of therapy.11 Two smaller studies of 82 and 60 adolescents found a similar weight-loss and plateau effect, with no observed changes in blood pressure.12,13
Orlistat (Xenical, Roche) is a reversible gastrointestinal lipase inhibitor. It reduces absorption of intact cholesterol and triglycerides by approximately 16 grams a day in a typical diet consisting of 30% fat. The recommended starting dose is 120 mg three times daily with meals. This is the same medication supplied in the over-the-counter medication program Alli (GlaxoSmithKline), which combines dietary and activity modification recommendations along with the nonprescription dose of orlistat (60 mg three times a day).14 Fat-soluble vitamin supplementation (A, D, E, and K) is recommended with this agent.15
Orlistat was FDA approved in 2003 for children aged ≥12 years. Side effects are those expected from luminal blockade of fat absorption, namely steatorrhea, flatus, and staining of the underwear. Two studies have looked at tolerability, efficacy, and side effects of orlistat in adolescents. The larger, a 54-week randomized controlled trial of 539 adolescents, showed a very slight decrease in BMI of 0.55 kg/m² which attenuated at week,12 compared with a BMI increase of 0.31 kg/m² with placebo. This amounts to an average weight gain at 1 year of 0.55 kg in the orlistat group compared with a 3.14-kg weight gain in the control group. Gallstone development was noted in seven out of 539 (1.3%).16 A smaller sample of 20 patients demonstrated a 5.4-kg weight loss in the intervention group at 6 months, compared with a 1.8-kg weight gain in the control group. Three patients (15%) dropped out due to side effects, and those remaining had attenuated symptoms after 2 weeks of therapy.17
Preliminary research suggests that metformin may have efficacy for weight control in selected insulin-resistant patients18 but has not been adequately evaluated and is not currently approved for this indication.
Bariatric Surgery (R Chung)
There is growing interest in the surgical management of severe adolescent obesity. In adults, the SOS (Swedish Obese Subjects) study recruited 4,047 obese adults for a prospective, controlled trial examining the health effects of weight reduction. At 10-year follow-up, weight relative to baseline (mean initial BMI 41 kg/m²) had decreased 16.1% in those who underwent surgery but increased by 1.6% in patients treated only with conventional measures.1,2 Weight-loss surgery has been performed in adolescents since the late 1970s, and the number of procedures performed tripled between 2000 and 2003.3 Weight-loss surgery in adolescents, however, still constitutes only 0.7% of all such procedures in the United States,4 resulting in a paucity of long-term outcomes data and nonstandardized patient selection criteria.
Roux-en-Y gastric bypass (RYGB) and adjustable gastric banding (AGB) are the most common procedures among both adolescents and adults. Currently, only RYGB is FDA approved for use in adolescents, although retrospective data for AGB suggest favorable outcomes.5 Jejunoileal bypass, vertical banded gastroplasty, banded gastric bypass, and biliopancreatic diversion are other less commonly used options. RYGB is a malabsorptive-restrictive procedure and generally produces more weight loss than purely restrictive procedures. AGB is a purely restrictive intervention in which an adjustable band is laparoscopically placed around the cardia of the stomach, creating a functional pouch. AGB is advantageous in that it does not alter the gastrointestinal physiology and is more readily reversible.5 (For more on bariatric surgery, pelase see the article on page 29.)
Early possible complications after RYGB include anastomotic leakage, wound infections, venous thromboembolism, gastrojejunal strictures, small bowel obstruction, fistulae, and symptomatic cholelithiasis.6 Not uncommon complications specific to AGB procedures include band slippage, gastric obstruction, and esophageal or gastric pouch dilatation.7 Limited data suggest that rates of these complications are for both adolescents and adults.6,7 Long-term complications can include deficiencies of iron, vitamin B12, vitamin D, and thiamine requiring lifelong supplementation. Interestingly, some studies have suggested that weight-loss surgery may be safer overall in adolescents as compared with adults,3,8 possibly due to a relative lack of complicating comorbidities in the younger patient population. Unresolved concerns specific to the adolescent patient remain, however, including potential negative effects on reproductive ability and pregnancy, and the effects of significant weight loss on linear growth.9
The current literature demonstrates that both gastric bypass and AGB in adolescents can lead to clinically significant and sustained decreases in BMI. One retrospective series of adolescents after RYGB reported a 37% reduction in BMI 1 year after surgery.10 Collins et al11 retrospectively examined a cohort of adolescents after RYGB and found similar results. Al-Qahtani12 retrospectively found a mean excess weight loss of 42% at 6 months and 60% at 1 year after AGB while Dillard et al7 reported rates of 34% and 52%, respectively. In addition to weight loss, improvements are commonly seen in insulin resistance, hypertriglyceridemia, diabetes, obstructive sleep apnea (OSA), depression, and quality-of-life metrics.10,13-15 The data are retrospective in nature, however, and limited by short-to-intermediate term outcome reporting with most follow-up intervals ranging between 1 and 3 years.
Patient selection for adolescent bariatric surgery is challenging. In adults, a BMI ≥40 kg/m² or >35 kg/m² with significant comorbidity is qualifying criteria for surgery.16 Among adolescents, significant variability in linear growth and puberty makes an absolute BMI cutoff impractical. As a BMI ≥99th percentile for age and gender defines the highest risk group, the use of Z-scores has been proposed to define subgroups of obese adolescents. Although there is no current definitive standard, the most widely accepted criteria for surgical intervention in adolescents is a BMI ≥40 kg/m² with one or more significant obesity-related disorders, or a BMI ≥50 kg/m² with more minor comorbidities.17,18 Severe comorbidities have generally been considered to include type 2 diabetes, OSA, severe steatohepatitis, and pseudotumor cerebri. Less severe comorbidities include hypertension, dyslipidemia, hyperinsulinemia, gastroesophageal reflux disease, mild steatohepatitis, venous stasis disease, panniculitis, stress urinary incontinence, arthropathies in weight-bearing joints, impairment in activities of daily living, and significant psychosocial distress secondary to obesity.5 Due to the adverse health effects of severe adolescent obesity and the accumulating evidence of favorable safety outcomes in this age group, the use of the lower adult BMI thresholds has been suggested by some groups.19
Additional patient selection criteria should include confirmation of inadequate weight loss after at least 6 months of organized attempts at weight management. A presurgical program should assess the patient's psychosocial status, the patient's and family's understanding and readiness to change, the patient's decisional capacity and maturity, and the viability of assent and consent. The patient's support system and familial situation should also be closely evaluated. The patient and family must also demonstrate commitment and capability to adhere to nutritional guidelines and supplementation postoperatively. Requirements include attainment or near-attainment of physiologic maturity (completing 95% of predicted adult stature based on bone age or reaching Tanner stage IV) and avoidance of pregnancy for at least 1 year postoperatively. The decision to pursue surgery should be made by a multidisciplinary team, which should include the surgeon, a pediatric obesity specialist, nurse, dietician, and pediatric psychologist or psychiatrist.18,20
The National Institute of Diabetes and Digestive and Kidney Diseases established the Longitudinal Assessment of Bariatric Surgery (LABS) consortium, a prospective observational study of adults undergoing bariatric surgery. Teen-LABS, a companion study to LABS, is also a prospective observational cohort study but with a focus on data collection in adolescent patients. In addition, the Pediatric Bariatric Study Group is currently conducting a prospective follow-up of 200 adolescents undergoing obesity surgery. With continued efforts, it is expected that substantive prospective data upon which to base further recommendations in adolescents will soon be available.
Literacy-based Approaches (A Russell)
A therapeutic tool for pediatric obesity that has not been explored until recently is the use of age-appropriate literature as a way to initiate and sustain behavior change. One of its main functions, aside from entertainment, is to model social behavior.1,2 Using literature as a therapeutic adjunct is especially appealing given the current predicament of compressed clinic appointments, as it provides a medium for patients to learn about healthy behaviors in a risk-free, nonjudgmental, self-paced format outside of the pediatrician's office. Several cross-sectional cohort studies and one prospective interventional study have suggested a positive correlation between reading and improved weight management in children, especially among adolescent girls.
A US study of 4,746 ethnically diverse adolescents (mean age, 14.9 years; 49.8% female) enrolled in Project EAT (Eating Among Teens) found that time spent reading was associated with healthier weight management behaviors among both boys and girls.3 Increased time spent reading was associated with increased leisure time physical activity, greater consumption of fruits and vegetables, decreased fat intake, and fewer soft drinks, fried foods, and snacks per day.3 Some of these findings were echoed in two Canadian studies. A cross-sectional cohort study of 743 Canadian adolescents (mean age, 15.1 years; 48.3% female) found that increased time spent in "productive sedentary behavior," such as reading, doing homework, or working on a computer, was associated with increased physical activity (odds ratio, 1.7; 95% confidence interval, 1.2–2.4).4 A secondary data analysis of 7,982 Canadian students (mean age, 15.61 years; 49.5% female) found that girls in particular were more likely to be active if they spent more time reading.5
It is important to note that girls spend significantly more time (2.4 hours per day) reading and doing homework than boys (1.9 hours per day) and less time in front of the television and computer.3 Additionally, Asian and white youth, as well as those in the highest socioeconomic group, spend the most time reading and doing homework.3 This indicates that literature as therapy may be more difficult to implement among boys and the black and Hispanic populations, as they may read less at baseline.
To date, there has been one interventional, prospective study examining the use of literature in improving weight control among adolescents. Eighty-one obese girls (mean BMI percentile 98.3) aged 9 to 13 years followed at the Duke Healthy Lifestyles Program, a comprehensive pediatric weight-management clinic, were randomized to three groups: one group received a novel about an overweight character who learns about appropriate nutrition and physical activity, one group received a novel featuring similar characters not addressing health issues, and one group received no novel.6 Over a 1- to 3-month follow-up period, a significantly greater reduction in BMI percentile was seen among girls who read about the overweight character (-0.71%) versus girls who read the other book (-0.33%; P=.03).6 Additionally, girls reading either book had a significantly greater reduction in BMI percentile (-0.49%) than girls who were not assigned a book (0.07%; P=.02).6 This suggests that age-appropriate fiction, particularly if it addresses health-oriented behaviors, can augment weight loss in adolescent females enrolled in a weight-management program. Given that all participants were treatment-seeking females, however, it is premature to generalize these results to the broader adolescent population.
These studies suggest that literature may be a novel medium to educate adolescents and motivate them to adopt healthier lifestyle habits, or at least decrease their exposure to other media known to contribute to weight gain.3,5 The influence of the literature content, however, must be further explored across genders and cultures before reading can be efficaciously "prescribed." Additionally, strategies to promote reading among groups who read less are needed to make extensive use of this therapy feasible. Although more research is needed, age-appropriate literature remains a promising intervention for pediatric obesity.
Sarah C. Armstrong, MD, is the Medical Director of the Healthy Lifestyles Program, in the Division of Pediatric Primary Care at Duke University Medical Center. She may be reached at sarah.c.armstrong@duke.edu; phone: 919-620-5315; or fax: 919-471-6390. (Duke Children's).
Richard Chung, MD, is a resident in the Departments of Internal Medicine and Pediatrics, Duke University Medical Center. He may be reached at richardjchung@gmail.com; phone: 919-323-0809; or pager: 919-970-4740.
Alexandra C. Russell, MSc, is in the Department of Internal Medicine and Pediatrics, Duke University Medical Center. She may be reached at russe060@mc.duke.edu.
Michelle Bailey, MD, is Director of Education, Duke Integrative Medicine, Consultant, Healthy Lifestyles Program and Medication Instructor in the Department of Pediatrics at Duke University Medical Center. She is also Director of Education, Dule Integrative Medicine. She may be reached at baile010@mc.duke.edu; phone: 919-660-6657; or fax: 919-681-0380.
Terrill Bravender, MD, MPH, is Chief of the Section of Adolescent Health at Nationwide Children's Hospital, and Associate Professor, The Ohio State University College of Medicine. He may be reached at bravender.1@osu.edu; phone: 614-722-2458; or fax: 614-355-3583.
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