Effects of Cyproheptadine on Growth and Behavior in Pediatric Feeding Disorders

BACKGROUND, SIGNIFICANCE, AND RATIONALE Failure to thrive or inadequate weight gain is a frequent complaint amongst patients seen by general pediatricians and pediatric gastroenterologists. The reasons behind this diagnosis vary widely including, but not limited to feeding disorders of diverse etiologies, poor environmental structure and inadequate intake, medication side effects, swallowing disorders, and a variety of underlying organic diseases. For most feeding disorders, behavioral feeding techniques and strategies to increase caloric intake is utilized to correct the suboptimal growth. However, feeding disorders are sometimes so imprinted that behavioral interventions may be insufficient to promote ideal growth or, if sufficient for growth, are inadequate in helping children avoid or graduate from nutritional support such as enteral tubes. For this reason, medications that promote and stimulate appetite and weight gain are frequently used in children with feeding disorders.

In pediatric gastroenterology practice, cyproheptadine is the most commonly used drug for appetite stimulation, weight gain, and feeding intolerance in younger children with feeding disorders. A first generation histamine and serotonin antagonist, cyproheptadine is thought to promote appetite stimulation and weight gain by increasing insulin-like growth factor-1 (IGF-1) concentration. It may also interact with receptors in the ventromedial hypothalamus and exert hormonal effects. While the exact mechanism of action is still being investigated, several studies have evaluated the benefits of cyproheptadine in select patient groups, including patients with cystic fibrosis, cancer, undernourished children, and children with feeding disorders. These studies have all reported that cyproheptadine promotes weight gain and stimulates appetite. Reported side effects of cyproheptadine in these studies are primarily related to drowsiness which tends to significantly improve or resolve within two weeks of use. Another undesired effect is the development of drug tolerance, i.e. tachyphylaxis. To avoid this, it is common clinical practice to cycle on and off the medication a few weeks each month.

While a few studies report outcomes of the use of cyproheptadine in children with feeding disorders or failure to thrive, these studies have enrolled only small patient cohorts and there are no randomized trials in children enrolled in a feeding team program. Two recent studies examined the role of cyproheptadine in patients who are undernourished or followed in pediatric feeding programs. However, a randomized study examining the effects of continuous cyproheptadine versus a fixed cycled medication dosing versus abstaining from medication has not been performed in the pediatric gastroenterology population.

OUTCOME MEASURES:

Number of Participants in Study: The total number of patients required for this study is 75 (25 in each group). The groups consist of three treatment arms: