Efficacy of a Novel Biphasic Controlled-Release Methylphenidate Formula in Adults With Attention-Deficit/Hyperactivity Disorder: Results of a Double-Blind, Placebo-Controlled Crossover Study

Umesh Jain, M.D.; Lily Hechtman, M.D.; Margaret Weiss, M.D.; Tahira S. Ahmed, M.D.; Joseph L. Reiz, B.Sc.; Graeme A. E. Donnelly, M.Sc.; Zoltan Harsanyi, B.Sc., M.L.S., M.B.A.; and Andrew C. Darke, Ph.D.

Objective: To evaluate the efficacy and safety of a new biphasic multilayer-release (MLR) methylphenidate formulation in a double-blind, placebo-controlled crossover study of adults with attention-deficit/hyperactivity disorder (ADHD).

Method: Adults 18 to 60 years of age with a DSM-IV diagnosis of ADHD entered a no-medication baseline week and were then randomly assigned to once-daily MLR methylphenidate or matching placebo. Patients were titrated to optimal effect over 1 to 3 weeks followed by 2 weeks of treatment on a stable dose. The same titration protocol was repeated with the alternate treatment. Clinical Global Impressions scale (CGI) and Conners' Adult ADHD Rating Scales (Self-rated, CAARS-S, and Observer-rated, CAARS-O) were collected at weekly clinic visits. The study was conducted between October 2003 and April 2004.

Results: Fifty patients were randomly assigned to treatment, and 39 were analyzed in a per-protocol population (23 men, 16 women; mean age = 37.9 years). CGI-Improvement scores of subjects taking MLR methylphenidate were significantly improved compared with placebo (Global Improvement: 2.6 vs. 3.7; p = .0015). MLR methylphenidate produced improvements over placebo on the ADHD Index T scores of the CAARS-S (12.2 vs. 5.4 [change from baseline score]; p = .0083) and the CAARS-O (10.9 vs. 6.6 [change from baseline score]; p = .1404). The most frequent adverse events for MLR methylphenidate and placebo were headache (26% and 24%, respectively), anorexia (22% and 6%), insomnia (22% and 8%), nervousness (20% and 4%), and nausea (16% and 8%). There were no serious adverse events.

Conclusions: Once-daily MLR methylphenidate produces significant improvements in ADHD symptoms and situational behavior in adult patients with ADHD, with a prolonged duration of effect and minimal side effects, thus having the potential to improve compliance and, therefore, treatment outcomes in routine clinical use.

(J Clin Psychiatry 2007;68:268-277)

Received May 10, 2006; accepted Aug. 17, 2006. From the Centre for Addiction and Mental Health, Toronto, Ontario (Dr. Jain); the Montreal Children's Hospital, Montreal, Quebec (Dr. Hechtman); the Department of Psychiatry, University of British Columbia and the Children's & Women's Health Centre of British Columbia, Vancouver, British Columbia (Dr. Weiss); the ADD Clinic, Halifax, Nova Scotia (Dr. Ahmed); and Purdue Pharma, Pickering, Ontario (Mssrs. Reiz, Donnelly, and Harsanyi and Dr. Darke), Canada.

This study was monitored and fully sponsored by Purdue Pharma, Pickering, Ontario, Canada.

A poster based on this study was presented at the joint 52nd annual meeting of the American Academy of Child and Adolescent Psychiatry/Canadian Academy of Child and Adolescent Psychiatry; October 18-23, 2005; Toronto, Ontario, Canada.

Dr. Jain has received grant/research support from Eli Lilly, Purdue, and Janssen-Ortho and has received honoraria from and is a member of the speakers or advisory boards for Eli Lilly, Purdue, Janssen-Ortho, and Shire. Dr. Hechtman is a consultant to and has received grant/research support from Eli Lilly, Janssen-Ortho, Shire, GlaxoSmithKline, and Purdue; has received honoraria from Eli Lilly and Janssen-Ortho; and is a member of the speakers or advisory boards for Shire and Purdue. Dr. Weiss is a consultant to Janssen-Ortho, Novartis, Shire, Purdue, and Eli Lilly; has received grant/research support from Janssen-Ortho, Circa Dia, Shire, Purdue, and Eli Lilly; has received honoraria from Janssen-Ortho, Novartis, Eli Lilly, and Shire; and is a member of the speakers or advisory boards for Janssen-Ortho, Novartis, Shire, and Eli Lilly. Dr. Ahmed reports no additional financial or other relationships relevant to the subject of this article. Mssrs. Reiz, Donnelly, and Harsanyi and Dr. Darke are employees of Purdue Pharma, Pickering, Ontario, Canada.

Corresponding author and reprints: Graeme A. E. Donnelly, Purdue Pharma, 575 Granite Court, Pickering, Ontario, Canada, L1W 3W8 (e-mail: graeme.donnelly@purdue.ca).