How to cite this article: Kishnani PS, Sommer BR, Handen BL, Seltzer B, Capone GT, Spiridigliozzi GA, Heller JH, Richardson S, McRae T. 2009. The efficacy, safety, and tolerability of donepezil for the treatment of young adults with Down syndrome. Am J Med Genet Part A 149A:1641–1654.
The efficacy, safety, and tolerability of donepezil for the treatment of young adults with Down syndrome†
Article first published online: 15 JUL 2009
Copyright © 2009 Wiley-Liss, Inc.
American Journal of Medical Genetics Part A
Volume 149A, Issue 8, pages 1641–1654, August 2009
How to Cite
Kishnani, P. S., Sommer, B. R., Handen, B. L., Seltzer, B., Capone, G. T., Spiridigliozzi, G. A., Heller, J. H., Richardson, S. and McRae, T. (2009), The efficacy, safety, and tolerability of donepezil for the treatment of young adults with Down syndrome. Am. J. Med. Genet., 149A: 1641–1654. doi: 10.1002/ajmg.a.32953
- Issue published online: 23 JUL 2009
- Article first published online: 15 JUL 2009
- Manuscript Accepted: 21 APR 2009
- Manuscript Received: 14 NOV 2008
- Down syndrome;
- clinical trials
The objective of our study was to assess the efficacy and safety of donepezil in young adults with Down syndrome (DS) but no evidence of Alzheimer disease (AD). A 12-week, randomized, double-blind, placebo-controlled study with a 12-week, open-label extension was conducted. The intervention consisted of donepezil (5–10 mg/day) in young adults (aged 18–35 years) with DS, but no AD. The primary measure was the Severe Impairment Battery (SIB) test and secondary measures were the Vineland Adaptive Behavior Scales (VABS), the Rivermead Behavioral Memory Test for Children, and the Clinical Evaluation of Language Fundamentals, Third Edition. At baseline, 123 subjects were randomly assigned treatment with donepezil or placebo. During the double-blind phase, SIB scores improved significantly from baseline in both groups, with no significant between-group differences. During the open-label phase, SIB scores in the original donepezil group remained stable; the original placebo group showed an improvement similar to that seen in the double-blind phase. VABS scores improved for donepezil, but not placebo, during the double-blind phase (observed cases, P = 0.03; last observation carried forward, P = 0.07). Post hoc responder analyses were significant for donepezil using three of five response definitions (P ≤ 0.045). Adverse event rates were comparable to AD studies. In this first large-scale, multicenter trial of a pharmacological agent for DS, donepezil appears safe. Efficacy interpretation was limited for the primary measure due to apparent learning/practice and ceiling effects. Outcomes in post hoc analyses suggested efficacy in some, but not all subjects, consistent with phenotypic variability of DS. Additional studies are required to confirm potential benefits of donepezil in this population. © 2009 Wiley-Liss, Inc.