Modafinil in children and adolescents with attention-deficit/hyperactivity disorder: a preliminary 8-week, open-label study

Objective: In a 4-week, double-blind, placebo-controlled study, the attention-promoting agent modafinil improved symptoms of attention-deficit/hyperactivity disorder ( ADHD) in children and adolescents and was well tolerated. To assess the continued efficacy of modafinil and obtain additional safety data, an 8-week, open-label study was conducted as an extension to the double-blind study. Method: Two hundred and twenty children and young adolescents ( age range, 6 - 14 years) with ADHD who had completed 4 weeks of the double-blind period or had withdrawn for reasons other than an adverse event were enrolled. Patients received individually titrated doses of modafinil ( 100 - 400 mg), administered once daily or as a divided dose. Patients visited the clinic at open-label weeks 2, 4, and 8 for assessments of efficacy. Efficacy was assessed using the parent-or clinician-completed ADHD Rating Scale-IV ( ADHD-RS-IV) Home Version, the parent-completed Conners' ADHD/DSM-IV Scale Parent Version ( CADS-P), and the clinician-rated Clinical Global Impression of Improvement ( CGI-I) scale. Adverse events were monitored. Results: Modafinil improved symptoms on all ADHD rating scales and subscales during the open-label extension. Mean change ( baseline to final visit) in Total score on the ADHD-RS-IV was - 14.6 ( 95% CI: - 16.40 to - 12.70); and - 7.6 ( 95% CI: - 8.65 to - 6.62) and - 6.9 ( 95% CI: - 7.90 to - 5.94) in the Inattention and Hyperactivity impulsivity scores, respectively. The mean Total score [ SD] on the CADS-P decreased from baseline ( 74.4 [ 10.3]) to the final visit ( 63.2 [ 13.1]) ( change: - 11.2, 95% CI: - 13.08 to - 9.65). Fifty-three percent of patients were rated as much or very much improved on the CGI-I. Insomnia ( 13%) three and headache ( 10%) were the most common adverse events. No clinically meaningful changes were observed in physical examination findings, electrocardiography, blood pressure, pulse, or body temperature. Clinically significant changes ( increase or decrease) in body weight of 7% or more were observed for 30 patients ( 14%), with decreases ( mean, 3.2 kg) reported for 22 patients ( 10%) and increases ( mean, 3.7 kg) reported for eight patients ( 4%). Conclusion: Modafinil remained efficacious and well tolerated in children with ADHD, improving ADHD symptoms and overall clinical condition during the open-label study. Limitations of the study include open-label dosing and lack of a placebo control.