Pharmacological Aspects in the Management of Children and Adolescents with Prader-Willi Syndrome

Prader-Willi syndrome is a rare neurodevelopmental disorder that impacts the musculoskeletal, endocrine, pulmonary, neurologic, ocular, and gastrointestinal systems. In addition, individuals with Prader-Willi syndrome have issues with cognitive development, characteristic behavioral problems, and perhaps most profoundly, appetite control. Currently, the only US Food and Drug Administration-approved therapy for Prader-Willi syndrome is growth hormone, which has been Food and Drug Administration approved for > 20 years for the treatment of growth failure in Prader-Willi syndrome. Growth hormone has shown to improve many aspects of this syndrome, including final height, body composition, developmental milestones, and cognition, but it does not affect hyperphagia, which is the hallmark symptom of this condition. Over the past 15 years, there have been several medication trials for the treatment of hyperphagia in Prader-Willi syndrome, but thus far, all have failed to achieve Food and Drug Administration approval for a variety of reasons. However, hyperphagia is the most life-limiting symptom of Prader-Willi syndrome, thus new pharmacologic therapies are desperately needed. We review ongoing and recently completed clinical trials for hyperphagia. Other issues in Prader-Willi syndrome that significantly impact quality of life include excessive daytime sleepiness and severe behavioral problems. We examine the medication trials to address these issues.