A Comparison of Once-Daily and Divided Doses of Modafinil in Children With Attention-Deficit/Hyperactivity Disorder: A Randomized, Double-Blind, and Placebo-Controlled Study

Joseph Biederman, M.D.; James M. Swanson, Ph.D.; Sharon B. Wigal, Ph.D.; Samuel W. Boellner, M.D.; Craig Q. Earl, Ph.D.; and Frank A. Lopez, M.D.; for the Modafinil ADHD Study Group

Objective: This randomized, double-blind, placebo-controlled study assessed the efficacy and tolerability of several modafinil dosing regimens in children with attention-deficit/hyperactivity disorder (ADHD) to determine whether modafinil can be given once daily in pediatric ADHD.

Method: Children and adolescents (age range, 6-13 years) (N = 248) with DSM-IV-defined ADHD were enrolled in a 4-week, double-blind, placebo-controlled study, conducted February-May 2002. The group was assigned to receive oral (100-mg tablets) modafinil 300 mg once daily (300 mg in the morning followed by placebo at midday), modafinil 300 mg as a divided dose (100/200 mg or 200/100 mg), or matching placebo. In children weighing > = 30 kg, a higher dose of 400 mg (200/200 mg) was evaluated. Efficacy measures included the teacher-rated School Version and clinician-rated Home Version of the ADHD Rating Scale-IV and the parent-completed Conners' ADHD/DSM-IV Scales.

Results: 223 children completed the study. Those who received modafinil 300 mg once daily showed a significantly greater improvement (change from baseline) than those who received placebo in symptoms of ADHD across all rating scales and subscales (all p < .05). Divided 300-mg doses of modafinil provided some significant but inconsistent improvements in ADHD symptoms. In children weighing > = 30 kg, modafinil 400 mg (200/200 mg) was significantly superior to placebo on clinician- and parent-completed scales (all p < .05). Insomnia was the only adverse event to occur with significantly greater frequency in a modafinil group (200/100) than in the placebo group (14% vs. 2%) (p = .03).

Conclusion: Modafinil significantly improved ADHD symptoms in children. Once-daily dosing (300 mg) provided the most consistent improvement in symptoms. All dosing regimens of modafinil were well tolerated.

(J Clin Psychiatry 2006;67:727-735)

Received Dec. 14, 2005; accepted March 30, 2006. From the Department of Pediatric Psychopharmacology, Massachusetts General Hospital, Boston, Mass. (Dr. Biederman); Child Development Center, University of California, Irvine, Calif. (Drs. Swanson and Wigal); Neurology and Clinical Study Center, Little Rock, Ark. (Dr. Boellner); Cephalon, Inc., Frazer, Pa. (Dr. Earl); and Children's Developmental Center, P.A., Maitland, Fla. (Dr. Lopez).

This study was supported by Cephalon, Inc., Frazer, Pa.

The results of this study were presented in part at the 156th annual meeting of the American Psychiatric Association, May 17-22, 2003, San Francisco, Calif.

Financial disclosures and acknowledgments are listed at the end of the article.

Corresponding author and reprints: Joseph Biederman, M.D., Pediatric Psychopharmacology Research Unit, Massachusetts General Hospital, Yawkey Center for Outpatient Care-YAW-6A-6900, 32 Fruit St., Boston, MA 02114 (e-mail: jbiederman@partners.org).