A Double-Blind, Placebo-Controlled Trial of Dexmethylphenidate Hydrochloride and d,l-threo-Methylphenidate Hydrochloride in Children With Attention-Deficit/Hyperactivity Disorder - 24/08/11
, JAMES M. SWANSON, Ph.D., DAVID FEIFEL, M.D., Ph.D., R BART SANGAL, M.D., JOSEPHINE ELIA, M.D., CHARLES D. CASAT, M.D., JEROME B. ZELDIS, M.D., Ph.D., C KEITH CONNERS, Ph.D.ABSTRACT |
Objective: |
To evaluate the efficacy and safety of dexmethylphenidate hydrochloride (d-MPH, Focalin™) for the treatment of attention-deficit/hyperactivity disorder (ADHD) and to test an a priori hypothesis that d-MPH would have a longer duration of action than d,l-threo-methylphenidate (d,l-MPH).
Method: |
This was a randomized, double-blind study conducted at 12 U.S. centers. One hundred thirty-two subjects received d-MPH (n = 44), d,l-MPH (n = 46), or placebo (n = 42) twice daily for 4 weeks, with titration of the dose based on weekly clinic visits. The primary efficacy variable was change from baseline to last study visit on teacher-completed Swanson, Nolan, and Pelham Rating Scale (Teacher SNAP). Secondary efficacy measures included the change on parent-completed SNAP (Parent SNAP), Clinical Global Impressions Scale-Improvement (CGI-I) score, and Math Test performance. Assessments at home in late afternoon were included to test the hypothesis that d-MPH would have a longer duration of efficacy than d,l-MPH. Safety was assessed through monitoring occurrence and severity of adverse events and discontinuations related to them.
Results: |
Treatment with either d-MPH (p = .0004) or d,l-MPH (p = .0042) significantly improved Teacher SNAP ratings compared with placebo. The d-MPH group showed significant improvements compared with placebo on the afternoon Parent SNAP ratings (p = .0003) and scores on the Math Test (p = .0236) obtained late in the afternoon at 6:00 p.m. Sixty-seven percent of patients showed improvement on d-MPH and 49% on d,l-MPH based on CGI-I scores. Both d-MPH and d,l-MPH were well tolerated, no patient in the d-MPH group and only two patients each in the d,l-MPH and placebo groups discontinued the study.
Conclusions: |
For the treatment of ADHD, an average titrated dose of 18.25 mg/day of d-MPH is as efficacious and safe as an average titrated dose of 32.14 mg/day of d,l-MPH. Both active treatments have large effect sizes. Thus, d-MPH and d,l-MPH appear to provide similar efficacy, and d-MPH may have longer duration of action after twice-daily dosing, but additional studies are needed to determine the statistical and clinical significance of this possibility.
Le texte complet de cet article est disponible en PDF.Key Words : attention-deficit/hyperactivity disorder, dexmethylphenidate, duration of action
Plan
| This study was supported by Celgene Corporation. The authors acknowledge Daniel Coury, M.D., Brian McConville, M.D., Donna Palumbo, Ph.D., Steve Pliszka, M.D., and Ralph W. Richter, M.D., for their contribution to the completion of the study. Disclosure: Dr. Wigal has served as a consultant for Alza, Celltech, McNeil Consumer & Specialty Pharmaceuticals, Novartis Pharmaceuticals Corporation, and Shire US Inc. She has received research support from Alza, Celgene, Celltech, Cephalon, Eli Lilly and Company, Janssen Pharmaceuticals, Inc., McNeil Consumer & Specialty Pharmaceuticals, Novartis Pharmaceuticals Corporation, and Shire US Inc. and also has served on the speakers’ bureau of Alza, Celgene, Celltech, Cephalon, Eli Lilly and Company, Janssen Pharmaceuticals, Inc., McNeil Consumer & Specialty Pharmaceuticals, Novartis Pharmaceuticals Corporation, and Shire US Inc. Dr. Swanson has served as a consultant for Alza, Celgene, Celltech, Cephalon, Eli Lilly and Company, Janssen Pharmaceuticals, Inc., McNeil Consumer & Specialty Pharmaceuticals, Novartis Pharmaceuticals Corporation, Shire US Inc., and Targacept, Inc. He has received research support from Alza, Celgene, Celltech, Cephalon, Eli Lilly and Company, Janssen Pharmaceuticals, Inc., McNeil Consumer & Specialty Pharmaceuticals, Novartis Pharmaceuticals Corporation, and Shire US Inc. Dr. Swanson serves on the speakers’ bureau of Alza, Celgene, Celltech, Cephalon, Eli Lilly and Company, Janssen Pharmaceuticals, Inc., McNeil Consumer & Specialty Pharmaceuticals, Novartis Pharmaceuticals Corporation, and Shire US Inc. Dr. Zeldis is the Chief Medical Officer and Vice President of Medical Affairs of Celgene Corporation. As such, he is salaried by Celgene and is a stockholder. In addition, he owns in his personal portfolio a variety of biopharmaceutical stocks including Allos, Johnson and Johnson, and Merck. He is on the Board of Directors of Semorex, a technology company. Dr. Conners received a fee for consultation on the protocol for the study. |
Vol 43 - N° 11
P. 1406-1414 - novembre 2004 Retour au numéro
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