Efficacy and safety of modafinil film-coated tablets in children and adolescents with or without prior stimulant treatment for attention-deficit/ hyperactivity disorder: Pooled analysis of 3 randomized, double-blind, placebo-controlled studies

University of California, Irvine, Child Development Center, Irvine, CA, USA.
The Primary Care Companion to The Journal of Clinical Psychiatry 02/2006; 8(6):352-60.
Source: PubMed


Objective: This report evaluated the efficacy and tolerability of modafinil film-coated tablets in children and adolescents with attention-deficit/hyperactivity disorder (ADHD), diagnosed using DSM-IV-TR criteria, who did or did not receive prior treatment with stimulants for ADHD by examining pooled data from 3 randomized, double-blind, placebo-controlled studies. Method: Three patient populations were evaluated: (1) all patients (i.e., all-patient group), (2) patients who were treated previously with stimulants (i.e., prior-stimulant group), and (3) patients who either were treated previously with ADHD medications other than stimulants or were not treated with any medications for ADHD (i.e., medication- or stimulantnaive group). Tolerability was evaluated by monitoring adverse events reported by both patients and parents. The 3 studies were conducted between November 2003 and June 2004. Results: Of 638 patients randomized, 633 received modafinil (N = 420) or placebo (N = 213), 303 had received prior stimulant treatment (modafinil, 194; placebo, 109), and 330 had no prior stimulant experience (modafinil, 226; placebo, 104). Modafinil improved symptoms of ADHD, as assessed by ADHD-RS-IV School Version total scores (mean change from baseline to final visit compared with placebo) in the all-patient group (-16.4 vs. -8.3) (p < .0001), the prior-stimulant group (-14.2 vs. -9.3) (p < .001), and the medication-or stimulant-naive group (-18.3 vs. -7.3) (p < .0001). Similar improvements were observed on the ADHD-RS-IV Home Version and for overall clinical condition. Insomnia, headache, and decreased appetite were the most commonly reported adverse events. Discontinuation because of adverse events was similar in the modafinil and placebo groups (5% vs. 3%). Conclusions: This post hoc analysis extends previous findings that modafinil was well tolerated and improved the symptoms and behaviors of ADHD at school and at home as assessed by teachers, parents, and clinicians and improved patients' overall clinical condition. Improvements were shown regardless of history of stimulant use.

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Available from: James Swanson, Dec 24, 2014
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    • "Severity of the ADHD symptoms were rated (with a score from 0 to 3) before training, after 6, 10, 20, 30 training sessions, and 6 months after the end of the training period. Global improvement was also included as a measure of efficacy and was assessed in the final interview with the parents using the Clinical Global Impressions-Improvement ADHD and EEG-neurofeedback 279 scale (CGI-I; Wigal et al. 2006). The CGI-I is a widely used scale to evaluate clinical effects in intervention studies. "
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    ABSTRACT: Electroencephalography (EEG)-neurofeedback has been shown to offer therapeutic benefits to patients with attention-deficit/hyperactivity disorder (ADHD) in several, mostly uncontrolled studies. This pilot study is designed to test the feasibility and safety of using a double-blind placebo feedback-controlled design and to explore the initial efficacy of individualized EEG-neurofeedback training in children with ADHD. Fourteen children (8–15 years) with ADHD defined according to the DSM-IV-TR criteria were randomly allocated to 30 sessions of EEG-neurofeedback (n = 8) or placebo feedback (n = 6). Safety measures (adverse events and sleep problems), ADHD symptoms and global improvement were monitored. With respect to feasibility, all children completed the study and attended all study visits and training sessions. No significant adverse effects or sleep problems were reported. Regarding the expectancy, 75% of children and their parent(s) in the active neurofeedback group and 50% of children and their parent(s) in the placebo feedback group thought they received placebo feedback training. Analyses revealed significant improvements of ADHD symptoms over time, but changes were similar for both groups. This pilot study shows that it is feasible to conduct a rigorous placebo-controlled trial to investigate the efficacy of neurofeedback training in children with ADHD. However, a double-blind design may not be feasible since using automatic adjusted reward thresholds may not work as effective as manually adjusted reward thresholds. Additionally, implementation of active learning strategies may be an important factor for the efficacy of EEG-neurofeedback training. Based on the results of this pilot study, changes are made in the design of the ongoing study. Electronic supplementary material The online version of this article (doi:10.1007/s00702-010-0524-2) contains supplementary material, which is available to authorized users.
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    • "It has been suggested that a higher dose of modafinil may be needed in children than that used for treatment of narcolepsy (Keating and Raffin, 2006). Recently, a few trials have shown that modafinil significantly improved symptoms of ADHD both at school and at home and was well tolerated by children and adolescents (Rugino and Copley, 2001; Biederman et al., 2005; Boellner et al., 2006; Greenhill et al., 2006; Swanson et al., 2006; Wigal et al., 2006). Abrupt discontinuation of modafinil was not associated with symptoms of withdrawal or with rebound of symptoms of ADHD (Swanson et al., 2006). "
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    • "As in the previous haloperidol study, we assessed the drug effect on responses to actual slot machine gambling in PG subjects. Modafinil is used for the treatment of narcolepsy but has also proven effective in the treatment of ADHD and cocaine addiction [105] [106]. In experiments , acute doses of modafinil improve impulse control and reduce risk-taking in ADHD subjects [107], and also reduce the rewarding effects of injected or smoked cocaine in cocaine abusers [108] [109]. "
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