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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.

Abstract

OBJECTIVE

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.

METHOD

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.

RESULTS

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).

CONCLUSION

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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  • Authors+Show Affiliations

    ,

    University of California at Irvine Child Development Center, 19722 MacArthur Boulevard, Irvine, CA 92627-4480, USA. jmswanson@uci.edu

    , , , , ,

    Source

    The Journal of clinical psychiatry 67:1 2006 Jan pg 137-47

    MeSH

    Adolescent
    Attention Deficit Disorder with Hyperactivity
    Benzhydryl Compounds
    Body Weight
    Central Nervous System Stimulants
    Chemistry, Pharmaceutical
    Child
    Dose-Response Relationship, Drug
    Double-Blind Method
    Drug Administration Schedule
    Female
    Humans
    Male
    Modafinil
    Placebos
    Substance Withdrawal Syndrome
    Tablets
    Treatment Outcome

    Pub Type(s)

    Comparative Study
    Journal Article
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    16426100

    Citation

    Swanson, James M., et al. "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." The Journal of Clinical Psychiatry, vol. 67, no. 1, 2006, pp. 137-47.
    Swanson JM, Greenhill LL, Lopez FA, et al. 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. J Clin Psychiatry. 2006;67(1):137-47.
    Swanson, J. M., Greenhill, L. L., Lopez, F. A., Sedillo, A., Earl, C. Q., Jiang, J. G., & Biederman, J. (2006). 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. The Journal of Clinical Psychiatry, 67(1), pp. 137-47.
    Swanson JM, et al. 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. J Clin Psychiatry. 2006;67(1):137-47. PubMed PMID: 16426100.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - 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. AU - Swanson,James M, AU - Greenhill,Laurence L, AU - Lopez,Frank A, AU - Sedillo,Andrew, AU - Earl,Craig Q, AU - Jiang,John G, AU - Biederman,Joseph, PY - 2006/1/24/pubmed PY - 2006/3/29/medline PY - 2006/1/24/entrez SP - 137 EP - 47 JF - The Journal of clinical psychiatry JO - J Clin Psychiatry VL - 67 IS - 1 N2 - OBJECTIVE: 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. METHOD: 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. RESULTS: 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). CONCLUSION: 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. SN - 0160-6689 UR - https://www.unboundmedicine.com/medline/citation/16426100/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_ L2 - http://www.psychiatrist.com/jcp/article/pages/2006/v67n01/v67n0120.aspx DB - PRIME DP - Unbound Medicine ER -