title: Oxytocin treatment in children with Prader-Willi syndrome: A double-blind, placebo-controlled, crossover study.
abstract: Prader-Willi syndrome (PWS) is a rare, complex multisystem genetic disorder which includes hypothalamic dysfunction, hyperphagia, cognitive and behavioral problems, increased anxiety, and compulsive behaviors. Individuals with PWS have a deficit of oxytocin producing neurons in the paraventricular nucleus of the hypothalamus. Oxytocin plays a role in regulation of feeding behaviors, social interactions, and emotional reactivity, which are all issues that significantly affect the quality of life for individuals with this syndrome. We performed a double-blind, placebo-controlled, crossover study in 24 children with PWS at three academic institutions using 5 days of intranasal oxytocin (IN-OT) or 5 days of intranasal placebo spray, followed by a 4 week washout period, and then patients returned for 5 days of treatment with the alternate source. Questionnaires, including the Aberrant Behavior Checklist, Social Responsiveness Scale, Repetitive Behavior Scale - Revised, and the Hyperphagia Questionnaire, as well as Clinical Global Impression scales were administered. Blood testing for sodium, potassium, and glucose levels on days 2, 4, and 6, and a 24 hr diet recall. All scales factor improvement from Day 3 to Day 6 favored oxytocin over placebo. No single factor showed a statistically significant difference (P < 0.05) between groups at Day 6. The drug effect appeared to be diminished at Day 14. There was no evidence of a difference between oxytocin and placebo in safety lab parameters, 60 min post dose vital signs, weight, or diet parameters. The results from this study suggest that low dose intranasal oxytocin is safe for individuals with PWS and may result in reduction in appetite drive, and improvements in socialization, anxiety, and repetitive behaviors. Further, long-term studies with a larger population of participants are necessary to confirm these findings. The results of this study are encouraging that oxytocin may be a safe and effective treatment for many of the issues that negatively impact individuals with PWS.
authors.affiliation: Departmentof Pediatrics College of Medicine, University of Florida, Gainesville, Florida.
authors.forename: Jennifer L
authors.identifier: http://orcid.org/0000-0003-4370-3438
authors.initials: JL
authors.lastname: Miller
authors.affiliation: Health Informatics Institute, University of South Florida, Tampa, Florida.
authors.forename: Roy
authors.initials: R
authors.lastname: Tamura
authors.affiliation: Departments of Psychiatry and Behavioral Sciences and Pediatrics, Kansas University Medical Center, Kansas City, Kansas.
authors.forename: Merlin G
authors.identifier: http://orcid.org/0000-0002-2911-0524
authors.initials: MG
authors.lastname: Butler
authors.affiliation: Division of Genetics and Genomics, Department of Pediatrics, University of California Irvine, Irvine, California.
authors.forename: Virginia
authors.initials: V
authors.lastname: Kimonis
authors.affiliation: Departmentof Pediatrics College of Medicine, University of Florida, Gainesville, Florida.
authors.forename: Carlos
authors.initials: C
authors.lastname: Sulsona
authors.affiliation: Department of Pediatrics, Division of Genetics and Metabolism, Loma Linda University Medical school, Loma Linda, California.
authors.forename: June-Anne
authors.initials: JA
authors.lastname: Gold
authors.affiliation: Departmentof Pediatrics College of Medicine, University of Florida, Gainesville, Florida.|Center for Epigenetics, College of Medicine, University of Florida, Gainesville, Florida.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Driscoll
mesh_terms: D002648:Child; D002675:Child, Preschool; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D010121:Oxytocin / Q000008:administration & dosage*; D011188:Potassium / Q000097:blood; D011218:Prader-Willi Syndrome / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D011788:Quality of Life; D012964:Sodium / Q000097:blood; D011795:Surveys and Questionnaires; D016896:Treatment Outcome
chemical_list: D010121:Oxytocin; D012964:Sodium; D011188:Potassium
keywords: Prader-Willi syndrome; hyperphagia; oxytocin