ARTICLES
A Randomized, Double-Blind, Placebo-Controlled Study of Modafinil Film-Coated Tablets in Children and Adolescents with Attention-Deficit/Hyperactivity Disorder

https://doi.org/10.1097/01.chi.0000205709.63571.c9Get rights and content

ABSTRACT

Objective

To evaluate the efficacy and tolerability of modafinil in children and adolescents, ages 7 to 17, with attention-deficit/hyperactivity disorder (ADHD).

Method

In this 9-week, double-blind, flexible-dose study, patients were randomized to once-daily modafinil (170-425 mg) or placebo. Assessments included ADHD Rating Scale-IV (ADHD-RS-IV) School and Home Versions and Clinical Global Impression of Improvement (CGI-I) scale.

Results

Two hundred patients were randomized. Modafinil produced significant reductions in ADHD-RS-IV total scores at school (n = 128; mean change ± SD: −17.5 ± 13.1 points) compared with placebo (n = 66; −9.7 ± 10.3 points; p < .0001). Similarly, modafinil reduced ADHD-RS-IV total scores at home compared with placebo (−17.6 ± 13.3 versus −7.5 ± 11.8 points; p < .0001). Fifty-two percent of patients randomized to modafinil and 18% of those randomized to placebo met prestudy criteria for responder on the CGI-I (p < .0001). Randomization to modafinil was associated with significantly more insomnia, headache, decreased appetite, and weight loss than randomization to placebo, but discontinuation attributed to adverse events did not differ statistically between treatment groups (modafinil, 5%; placebo, 6%).

Conclusion

Modafinil was well tolerated and reduced ADHD symptoms at school and home compared with placebo.

Section snippets

Patients

Eligible patients met the following inclusion criteria: 6 to 17 years of age, inclusive; the National Institute of Mental Health Diagnostic Interview Schedule for Children, Fourth Edition (DISC-IV) was used to establish the patients' diagnosis of ADHD using the full DSM-IV diagnostic criteria (American Psychiatric Association, 1994, Shaffer et al., 2000);Clinical Global Impression of Severity of Illness (CGI-S) rating of 4 or higher (moderately ill or worse) (Guy, 1976); weight and height

Patients and Dosing

A total of 200 patients were randomized; 131 received modafinil film-coated tablets and 67 received placebo (2 patients were not treated; Fig. 1). Seventy percent of patients completed the study, and discontinuation rates were higher in the placebo group (modafinil, 25%; placebo, 39%), with the majority of cases in both groups discontinuing because of a lack of efficacy. A total of 57 patients in the safety analysis set discontinued from the study (31 in the modafinil group and 26 in the

DISCUSSION

In this 9-week, double-blind, placebo-controlled study, modafinil film-coated tablets significantly improved ADHD symptoms compared with placebo on the ADHD-RS-IV School and Home Versions. Modafinilapos;s moderate effect size (0.60-0.78 SD) is similar to that of atomoxetine (Michelson et al., 2004), but smaller than methylphenidate (Greenhill et al., 2001). Taking the active drug was associated with improvements in inattention, hyperactivity, and impulsivity. Significantly more patients who

REFERENCES (38)

  • TE Wilens et al.

    The stimulants revisited

    Child Adolesc Psychiatr Clin N Am

    (2000)
  • American Academy of Child and Adolescent Psychiatry

    Practice parameter for the use of stimulant medications in the treatment of children, adolescents, and adults

    J Am Acad Child Adolesc Psychiatry

    (2002)
  • American Academy of Pediatrics

    Clinical practice guideline: diagnosis and evaluation of the child with attention-deficit/hyperactivity disorder

    Pediatrics

    (2000)
  • American Psychiatric Association

    Diagnostic and Statistical Manual of Mental Disorders

    (1994)
  • Biederman J, Lopez F, Swanson JM, Boellner S, Modafinil ADHD Study Group (2003), Modafinil improves ADHD symptoms in...
  • J Biederman et al.

    Efficacy and safety of modafinil film-coated tablets in children and adolescents with attention-deficit/hyperactivity disorder: results of a randomized, double-blind, placebo-controlled, flexible-dose study

    Pediatrics

    (2005)
  • CK Conners

    Conners' Parent Rating Scales-Revised: Short Form (CPRS-R:S)

    (1997)
  • V Deroche-Gamonet et al.

    Study of the addictive potential of modafinil in naive and cocaine-experienced rats

    Psychopharmacology

    (2002)
  • GJ DuPaul et al.

    ADHD Rating Scale-IV: Checklists, Norms, and Clinical Interpretation

    (1998)
  • Cited by (81)

    • Modafinil for the treatment of attention-deficit/hyperactivity disorder: A meta-analysis

      2017, Journal of Psychiatric Research
      Citation Excerpt :

      It is known to act on multiple areas of the ascending arousal and attention systems to increase frontal cortical activity (Lin et al., 1996). Numerous randomized clinical trials (Biederman et al., 2005; Greenhill et al., 2006) and open label studies (Boellner et al., 2006; Rugino and Copley, 2001) have shown that modafinil could be an effective and safe treatment option in ADHD. A post hoc analysis of data consisted of 3 randomized, double-blind, placebo-controlled trials (RCTs) further demonstrated that modafinil improved symptoms of ADHD compared with placebo (Wigal et al., 2006).

    • Body weight and basal metabolic rate in childhood narcolepsy: a longitudinal study

      2016, Sleep Medicine
      Citation Excerpt :

      Second, medications were continued in the patients with narcolepsy. Drugs such as methylphenidate, modafinil, and venlafaxine affect energy metabolism [41–43]. These drugs are normally prone to increase energy metabolism [41–43] and are unlikely to increase the false-positive results.

    • A preclinical evaluation of the discriminative and reinforcing properties of lisdexamfetamine in comparison to D-amfetamine, methylphenidate and modafinil

      2013, Neuropharmacology
      Citation Excerpt :

      Modafinil is an unusual stimulant with enigmatic pharmacology (see reviews by Minzenberg and Carter, 2008; Heal et al., 2012a). Although its clinical development as a treatment for ADHD was terminated due to safety concerns, modafinil has been shown unequivocally to improve symptoms in children and adolescents with ADHD in several, randomised, double-blind, placebo-controlled, clinical trials (Biederman et al., 2006; Swanson et al., 2006; Greenhill et al., 2006). Modafinil has a C-IV classification in the USA, but it is not a CD in the UK.

    View all citing articles on Scopus

    Statistical expert: John G. Jiang, Ph.D.

    The authors acknowledge V. Arnold (Memphis, TN), L. Montgomery-Barefield (Birmingham, AL), M. Chandler (Chapel Hill, NC), R. Dean (Danville, IN), J. Ferguson (Salt Lake City, UT), J. Lee (Charlotte, NC), A. Levine (Boulder, CO), R. Lipetz (Spring Valley, CA), A. Padilla (Miami Beach, FL), R. Northam (Norfolk, VA), J. Pahl (Oklahoma City, OK), R. Reichler (Seattle, WA), E. Sarkis (Gainesville, FL), H. Schub (Atlanta, GA), M. Molina (Hialeah, FL), and ePharma Learning Inc. (Conshohocken, PA).

    Disclosure: Dr. Greenhill receives research support from Eli Lilly and Co., Novartis Pharmaceuticals, and Shire; and he is a consultant for Novartis, Janssen Pharmaceutica, McNeil Consumer & Specialty Pharmaceuticals, and Pfizer. Dr. Biederman receives research support from Abbott Laboratories, Bristol-Myers Squibb, Cephalon, Eli Lilly, Janssen, McNeil, NeuroSearch, New River Pharmaceuticals, Pfizer, and Shire; and he serves on speakers' bureaus for Cephalon, Eli Lilly, McNeil, and Shire, and is on advisory boards for Cephalon, Eli Lilly, Janssen, McNeil, Novartis, and Shire. Dr. Boellneris an investigator for Celltech, New River Pharmaceuticals, Novartis, and Shire. Dr. Rugino receives research support from Cephalon and is on speakers' bureaus for Cephalon and Novartis. Dr. Sangal receives research support from Cephalon, Eli Lilly, Merck, Organon, and Sanofi-Aventis. Drs. Earl and Jiangare employees of Cephalon. Dr. Swanson receives research support from, serves on the speakers' bureaus for, and is a consultant to ALZA, Celgene, Celltech, Cephalon, Eli Lilly, Janssen, McNeil, Novartis, and Shire; he is also a consultant for Targacept.

    View full text