Modafinil film-coated tablets in children and adolescents with attention-deficit/hyperactivity disorder: Results of a randomized, double-blind, placebo-controlled, fixed-dose study followed by abrupt discontinuation

University of California at Irvine Child Development Center, 19722 MacArthur Boulevard, Irvine, CA 92627-4480, USA.
The Journal of Clinical Psychiatry (Impact Factor: 5.5). 02/2006; 67(1):137-47.
Source: PubMed


The objective of this fixed-dose study was to determine the efficacy and safety of a new formulation of modafinil (modafinil film-coated tablets) in children and adolescents with attention-deficit/hyperactivity disorder (ADHD). In addition, the effect of abrupt discontinuation of modafinil was evaluated in a 2-week observation period.
Patients aged 6 to 17 years with DSM-IV-TR-defined ADHD were randomly assigned to 7 weeks of double-blind treatment with modafinil or placebo in a 2:1 ratio, followed by abrupt discontinuation of modafinil and a 2-week, double-blind observation period in which 46% of patients receiving modafinil were switched to placebo without tapering and half continued to receive modafinil. Study drug was administered once daily and titrated over the first 7 to 9 days to daily doses of 340 mg for patients < 30 kg or 425 mg for patients > or = 30 kg. Assessment instruments included the Attention-Deficit/ Hyperactivity Disorder Rating Scale-IV (ADHD-RS-IV) School and Home Versions and Clinical Global Impressions-Improvement scale (CGI-I). The study was conducted from November 2003 to June 2004.
A total of 190 patients were randomly assigned to receive modafinil (340 mg, N = 44; 425 mg, N = 82) or placebo (N = 64). 189 patients were evaluated for safety. Modafinil significantly improved symptoms of ADHD as shown by reductions in ADHD-RS-IV School Version total scores compared with placebo at all visits (p < or = .009), including the final visit of the double-blind phase (p < .0001). With modafinil, ADHD-RS-IV School Version mean total scores changed from 37.8 at baseline to 29.3 at week 1 and 20.7 at final visit; corresponding placebo values were 36.6, 32.8, and 28.4, respectively; effect size at final visit was 0.76 (95% CI = 0.63 to 0.88). Total scores on the ADHD-RS-IV Home Version were also significantly reduced at all visits (p < or = .022) and final visit (p = .001) in patients receiving modafinil compared with those receiving placebo. Significantly higher proportions of patients receiving modafinil were rated "much improved" or "very much improved" in overall clinical condition (CGI-I) at all visits compared with patients receiving placebo (p < .001). No withdrawal symptoms were observed when modafinil was abruptly discontinued at the beginning of the final 2-week observation period. Modafinil was generally well tolerated. Insomnia, headache, and decreased appetite were the most commonly reported adverse events. Sixty-three percent of patients who received modafinil completed the study; 13% discontinued because of lack of efficacy; 10%, because of adverse events; and 13%, for other reasons (e.g., consent withdrawn, lost to follow-up).
Modafinil significantly improved symptoms of ADHD both at school and at home and was well tolerated by children and adolescents. Abrupt discontinuation of modafinil was not associated with symptoms of withdrawal or with rebound of symptoms of ADHD.

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    • "In the past decade, there has been a marked increase in offlabel use of modafinil for a variety of indications (Peñaloza et al. 2013). As a nonamphetamine stimulant with low abuse liability, modafinil may be a safe alternative for treatment of fatigue syndrome and psychiatric disorders such as treatmentresistant depression and attention deficit/hyperactivity disorder (Minzenberg and Carter 2008; Swanson et al. 2006). Despite the widespread clinical use of modafinil, the precise mechanisms underlying its therapeutic efficacy are complex and not well understood (for review, see Ballon and Feifel 2006; Minzenberg and Carter 2008). "
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    Psychopharmacology 02/2015; 232(14). DOI:10.1007/s00213-015-3884-3 · 3.88 Impact Factor
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    • "In addition, modafinil has been proposed to improve concentration (Minzenberg and Carter, 2008) and to lessen the symptoms of attention-deficit hyperactivity disorder (ADHD) (Turner et al., 2004; Swanson et al., 2006). It has been also used to treat cocaine/ methamphetamine abuse and depression (for a review see Ballon and Feifel, 2006). "
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