Treatment of Pediatric and Adolescent Obesity

The prevalence of overweight in US children and adolescents has reached alarming levels. The proportion of children and adolescents who are overweight, defined as a body mass index exceeding the 95th percentile for age and sex based on norms from the 1960s, has tripled in the past 3 decades.¹ This dramatic increase in overweight has not been confined to US children and adolescents; pediatric overweight is also increasing in other countries.^{2 - 4} Greater body weight has been found to predispose children and adolescents to many of the medical complications of obesity found in adults, such as hypertension,⁵ dyslipidemia,⁶ impaired glucose homeostasis,^{7 - 8} steatohepatitis,⁹ sleep apnea,¹⁰ and intracranial hypertension,¹¹ and to problems unique to childhood and adolescence, including accelerated pubertal¹² and skeletal¹³ development and orthopedic disorders, such as slipped capital femoral epiphysis.¹⁴

In this issue of THE JOURNAL, Schwimmer and colleagues¹⁵ report that severely obese children and adolescents who seek obesity treatment have more than a 5-fold increased risk of reporting a low health-related quality of life compared with a reference sample of healthy children and adolescents—a risk similar to that previously described for children and adolescents diagnosed as having cancer. Overweight during childhood and adolescence also appears to be an important independent predictor of health risks and mortality in later life, even when adult weight is taken into account.¹⁶ Thus, it seems clear that one of the most compelling medical challenges of the 21st century is to develop effective strategies to prevent and treat pediatric obesity.

Successful methods to prevent pediatric overweight remain elusive, but some innovative approaches, such as techniques to decrease television viewing by children and adolescents,¹⁷ are being actively investigated. Although some data suggest that behavioral treatment of obesity may be more effective for children and adolescents than for adults,¹⁸ even the best of studies find long-term weight reductions maintained in only about half of young children and adolescents treated with intensive behavioral modification.^{18 - 19} Successful behavioral programs are labor intensive, are not yet translated into versions that can be easily applied on the primary care level, and require intensive parental involvement which, for many families, is simply not realistic. Many clinicians also believe that behavioral treatment alone is not as effective in severely obese children and adolescents compared with those with lesser degrees of obesity. As a result, some investigators have turned to the study of pharmacotherapy for amelioration of pediatric obesity. Even though obesity is now viewed as a chronic disorder that requires continued treatment,²⁰ few controlled studies lasting more than a few weeks have examined the efficacy of medications to reduce body weight in children or adolescents.²¹

Also in this issue of THE JOURNAL, Berkowitz et al²² present a 6-month randomized controlled trial of sibutramine, an anorexiant medication that blocks the reuptake of the neurotransmitters norepinephrine and serotonin. Sibutramine appears to be modestly effective for weight reduction in adults over periods as long as 2 years.²³ During the first 6 months of treatment, adults who follow a reduced-calorie diet and take sibutramine typically lose 5% to 8% of their initial body weight vs 1% to 4% in placebo-treated patients.²⁰ The major adverse effects of sibutramine include increases in blood pressure and pulse rate great enough to warrant discontinuation of sibutramine in up to 5.3% of treated adults.

Berkowitz et al randomly assigned 82 adolescents with a body mass index between 32 and 44—the majority of whom had evidence of obesity-related comorbid conditions (R. Berkowitz, written communication, March 14, 2003)—to receive intensive behavioral therapy and placebo or intensive behavioral therapy and sibutramine for 6 months. The investigators then offered all study participants open-label sibutramine for an additional 6 months along with a somewhat less intensive behavioral therapy. The study had excellent retention with all but 8 participants returning for follow-up at 6 months. Adolescents treated with behavioral therapy and sibutramine lost significantly more weight (mean [SD] of −7.9 [6.3] kg) than those who received behavioral therapy and placebo (mean [SD] of −3.2 [6.1] kg) over the first 6 months. Further, a substantial portion of adolescents treated with behavioral therapy and sibutramine had weight losses that are considered medically significant. A decrement in initial body mass index by 10% was found in 40% of adolescents treated with behavioral therapy and sibutramine vs 15% of adolescents treated with behavioral therapy and placebo. Weight losses were largely maintained by those who continued taking sibutramine for another 6 months while attending behavioral therapy sessions.

These data are encouraging, but have some important limitations. First, the study design excluded adolescents who had a body mass index of more than 44 or who had already developed type 2 diabetes. Thus, those adolescents most severely affected by their obesity were not studied, and no conclusions can be drawn regarding the efficacy of sibutramine for reducing body weight in such adolescents. Second, adolescents participated in an intensive behavior modification program that included 13 weekly group sessions, followed by 6 biweekly group sessions over the first 6 months. Berkowitz et al found that adherence to the program independently accounted for a significant portion of the variance in lost body weight—more than that explained by sibutramine vs placebo. Intensive behavioral programs are costly, require specially trained staff, and are not often available in the community setting.

Third, and perhaps most important, sibutramine therapy caused increases in systolic blood pressure at 3 months (vs a decline in blood pressure in placebo-treated adolescents). The medication dose had to be reduced or discontinued in 44% of the sibutramine-treated adolescents during the first 6 months. Fourth, the improvements observed in the comorbid conditions associated with obesity, such as insulin resistance and dyslipidemia, were not different in the adolescents receiving sibutramine or placebo despite the greater weight losses of those taking sibutramine. Although the failure to detect a difference between groups may have been due to the study's relatively small sample size, given the increases in pulse rate and blood pressure observed in this study, it is not clear whether behavioral therapy and sibutramine improve the surrogate markers for cardiovascular disease in adolescents more than behavioral treatment alone.

Fifth, the study data are informative only for the effects of sibutramine over 6 to 12 months. Obesity is a chronic condition that requires lifelong efforts to control. It remains unknown whether sibutramine will continue to be effective for reducing body weight in adolescents in the long term and diminish the medical complications of their obesity. Nonetheless, this study is important because it indicates that pharmacotherapy, in combination with intensive behavioral treatment, can lead to clinically significant decreases in body weight in an adolescent population and can serve as a model for future studies.

As the number of children and adolescents with severe obesity and concomitant medical problems increases, the inclination for clinicians to consider intensive treatments, including pharmacotherapy and surgery,²⁴ becomes greater. Given the many ways in which children and adolescents differ from adults, physicians must not conclude that treatments found safe and effective in adults will have similar safety and effectiveness in pediatric and adolescent populations.

While it is appropriate to consider intensive treatments in severely obese adolescents with comorbid conditions,^{20 - 21} such treatments should be regarded as investigational at this time and should be performed as part of a closely monitored research study. Clinicians should consider referring severely obese children and adolescents to experienced, specialized pediatric obesity centers, so that intensive treatment can be performed by a team of professionals that may include physicians, dietitians, behaviorists, and exercise specialists with expertise in pediatric and adolescent medicine. Evidence-based guidelines²⁵ for treatment of pediatric and adolescent obesity would be useful, but current data are insufficient to generate them for children or adolescents. For now, expert opinion must serve as a guide for pediatric and adolescent obesity treatment.²⁶

Rapid advances in basic and clinical science are elucidating the complex genetic, psychosocial, metabolic, and environmental factors that contribute to the development of obesity and its comorbid conditions. This research will lead to improved methods for prevention and treatment of obesity in the years ahead. Researchers should be encouraged to include children and adolescents in clinical research studies of obesity prevention and treatment, so that the risks and benefits from therapeutic advances can be established in pediatric and adolescent populations.

At the present time, however, it remains exceedingly difficult for overweight children and adolescents to lose weight, and even more difficult for them to sustain that weight loss long term. The ultimate goal must be prevention of the development of overweight in children and adolescents.²⁷