Modafinil significantly improved symptoms in children with inattentive and combined subtypes of attention-deficit/hyperactivity disorder, based on data from 638 children aged 6–17 years.
Pooled results from one 7-week study and two 9-week studies showed that modafinil was well tolerated and improved attention-deficit hyperactivity disorder (ADHD) symptoms both at home and in school. The studies were funded by Cephalon Inc., which markets modafinil as Provigil in the United States.
Dr. Joseph Biederman of Massachusetts General Hospital, Boston, and Dr. Steven R. Pliszka of the University of Texas Health Science Center, San Antonio, reviewed the pooled data to analyze the effectiveness of modafinil on three ADHD subtypes: inattentive, combined, and hyperactive impulsive (J. Pediatr. 2008;152:394-9). Few studies have examined the effectiveness of drug treatments for ADHD by subtype.
In the 7-week study, children were randomized to receive 340 mg or 425 mg of modafinil or a placebo daily. In the 9-week studies, children were randomized to receive a flexible dose from 170 mg to 425 mg or a placebo daily. A total of 423 children received modafinil and 215 received a placebo.
The researchers used the ADHD-RS-IV School Version, which includes teacher and investigator ratings to assess symptoms.
Children in the inattentive and combined subgroups who received modafinil showed significant improvements in the ADHD-RS-IV School Version total scores, compared with placebo patients. Children in the hyperactive-impulsive subgroup who received modafinil showed a greater improvement in total scores (demonstrated by lower numbers) than placebo patients, but this difference was not statistically significant.
The average score for modafinil patients across all subgroups was 57 at the study's end versus 73 for placebo patients. Results were similar for scores on the ADHD-RS-IV Home Version, which were detailed in a separate analysis.
Forty-eight percent of the inattentive subgroup who received modafinil versus 15% of those who were given a placebo received “much improved” or “very much improved” ratings from investigators. Similarly, 44% of the combined subgroup who received modafinil versus 18% of those who received placebo were rated “much improved” or “very much improved” by the investigators.
Children in the inattentive and combined subtype groups who received modafinil showed significant improvements in subscale scores for cognitive problems/inattention, hyperactivity, and the ADHD index, compared with placebo patients.
The combined subtype of ADHD is the most commonly diagnosed and is most often associated with psychiatric comorbidity and other behavioral, social, and academic problems, the researchers noted. A total of 65% of the children met criteria for the combined ADHD subtype, and this group had the largest percentage (18%) of children who were ranked “severely ill” or “extremely ill” at baseline.
Dr. Biederman receives research support from multiple drug companies, including this study's sponsor, Cephalon (for whom he also serves as a speaker and a member of the advisory board). He also serves as a speaker and advisory board member for many other pharmaceutical companies.
Dr. Pliszka receives research support from Cephalon and Eli Lilly & Co., and serves on speakers bureaus sponsored by Shire Pharmaceuticals and McNeil.