Journal of Developmental and Physical Disabilities, Vol. 18, No. 1, March 2006 ( C  2006) DOI: 10.1007/s10882-006-9005-9 “N of 1” Trials of Methylphenidate in Two Children with Williams Syndrome and Attention Deficit Hyperactivity Disorder L. Zwaigenbaum, 1,4 P. Dick, 2 M. Handley-Derry, 3 M. Malone, 2 and S. Jacobson 2 Published online: 2 June 2006 Poor attention and motor restlessness are common in Williams syndrome (WS) children, and attention deficit hyperactivity disorder (ADHD) is at least as prevalent in WS as in other mentally handicapped groups. We determined the effectiveness of methylphenidate in two children with WS and ADHD. Each child underwent a double-blind dose-determining assessment to se- lect the optimum dose for “N of 1” trials, which consisted of single subject, placebo-controlled randomized controlled trials with multiple crossovers. A regimen of 5 mg in the morning and 2.5 mg at noon was determined by consensus for both trials. Response to MPH was assessed using parent and teacher Conners ratings, and analyzed separately for each child, using mixed model ANOVA. No significant differences in behavioral ratings between medication and placebo weeks were found during the “N of 1 trials.” We con- clude that methylphenidate was not superior to placebo in decreasing ADHD symptoms in these two children with Williams syndrome. KEY WORDS: Williams syndrome; attention deficit hyperactivity disorder; randomized con- trolled trials; methylphenidate; drug treatment. Williams Syndrome (WS) is a developmental disorder first described in 1961 (Williams et al., 1961), which results from a microdeletion at chromo- some 7q11.23 (Ewart et al., 1993). WS has a prevalence of approximately 1 McMaster Children’s Hospital, McMaster University, Hamilton, Ontario, Canada. 2 The Hospital for Sick Children, University of Toronto, Toronto, Canada. 3 University of Toronto, Toronto, Canada. 4 To whom correspondence should be addressed at Department of Paediatrics, Children’s Hospital, McMaster University, P.O. Box 2000, Hamilton, Ontario, Canada L8N 3Z5; e-mail: zwaigenb@mcmaster.ca. 45 1056-263X/06/0300-0045/0 C  2006 Springer Science+Business Media, Inc.