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.
    Journal of Neural Transmission 12/2010; 118(2):275-84. DOI:10.1007/s00702-010-0524-2 · 2.40 Impact Factor
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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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    ABSTRACT: Attention-deficit/hyperactivity disorder (ADHD) is the most common behavioral disorder in childhood, with an estimated prevalence worldwide of 7%-17% among school-aged children. Modafinil is a centrally acting agent that is structurally and pharmacologically different from stimulants such as amphetamine and methylphenidate. It has been reported that modafinil is effective in diminishing the symptoms of ADHD. The aim of the present study was to further evaluate, under double-blind and placebo-controlled conditions, the efficacy of modafinil for ADHD in children and adolescents. Patients were 46 outpatients, children (35 boys and 11 girls) between the ages of 6 and 15 who clearly met the DSM-IV-TR diagnostic criteria for ADHD. All study subjects were randomly assigned to receive treatment with modafinil in a film-coated tablet, 200-300 mg/day, depending on weight (200 mg/day for <30 kg and 300 mg/day for >30 kg) (group 1) or placebo (group 2) for a 6-week double-blind, randomized clinical trial. The principal outcome measure was the Teacher and Parent ADHD Rating Scale-IV. Patients were assessed by a psychiatrist at baseline, 14, 28 and 42 days after the medication started. At 6 weeks, modafinil produced a significantly better outcome on the Parent and Teacher Rating Scale scores than placebo. Decreased appetite was observed more often in the modafinil group. The results of this study indicate that modafinil significantly improved symptoms of ADHD, was well tolerated, and may open a new window in the treatment of children with ADHD.
    Psychiatry Research 05/2009; 168(3):234-7. DOI:10.1016/j.psychres.2008.06.024 · 2.47 Impact Factor
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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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    ABSTRACT: A variety of evidence suggests important commonalities in the neurochemical basis of reinforcement in pathological gambling (PG) and psychostimulant addiction. This article focuses on the parallel and specific roles that dopamine (DA) activation plays in these two disorders, beyond its generic role in reinforcement. A psychostimulant-mimetic model for PG is proposed based on evidence from the following domains: Acute subjective-behavioral effects of gambling and psychostimulants; Effects of anticipated rewards and uncertainty of reward delivery (key elements of gambling) on DA release; Relationship between DA release and positive arousal; Cross-priming of motivation for gambling by amphetamine; Effects of DA D2 antagonists on gambling and amphetamine reward; Effects of mixed D1-D2 antagonists on clinical symptoms of PG; Effects of DA D2 agonists on experimental measures of risk-taking, gambling, and induction of PG in patients with Parkinson's disease; Electrophysiological and cognitive disturbances associated with chronic exposure to gambling and psychostimulants, and the possible role of sensitization in these effects. Limitations of the model regarding the exclusive role of DA are discussed with particular reference to genetic risk, co-morbidity, and sub-types of PG. Suggestions for future research include isolating the roles of DA receptor subtypes in PG, and parallel within-subject assessment of DA manipulations on gambling and psychostimulant reinforcement in PG subjects and controls.
    Current Drug Abuse Reviews 02/2009; 2(1):11-25. DOI:10.2174/1874473710902010011
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