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Comparison of the clinical efficacy of twice-daily Ritalin® and once-daily Equasym™ XL with placebo in children with Attention Deficit/Hyperactivity Disorder

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Abstract

Objective

To compare the efficacy and safety of two methylphenidate (MPH) formulations—once-daily modified-release MPH (EqXL, Equasym™ XL) and twice-daily immediate-release methylphenidate (MPH-IR, Ritalin®)—and placebo in children with Attention Deficit/Hyperactivity Disorder (ADHD).

Methods

Children aged 6–12 years on a stable dose of MPH were randomized into a double-blind, three-arm, parallel-group, multi-center study and received 3 weeks of EqXL (20, 40, or 60 mg qd), MPH-IR (10, 20, or 30 mg bid) or placebo. Non-inferiority of EqXL to MPH-IR was assessed by the difference in the inattention/overactivity component of the overall teacher’s IOWA Conners’ Rating Scale on the last week of treatment (per protocol population). Safety was monitored by adverse events, laboratory parameters, vital signs, physical exam, and a Side Effect Rating Scale.

Results

The lower 97.5% confidence interval bound of the difference between MPH groups fell above the non-inferiority margin (−1.5 points) not only during the last week of treatment but during all three treatment weeks. Both MPH-treatment groups experienced superior benefit when compared to placebo during all treatment weeks (P < 0.001). All treatments were well tolerated.

Conclusions

EqXL given once-daily was non-inferior to MPH-IR given twice-daily. Both treatments were superior to placebo in reducing ADHD symptoms.

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References

  1. Elia J, Ambrosini PJ, Rapoport JL (1999) Treatment of attention-deficit hyperactivity disorder. New England J Med 340(10):780–788

    Article  CAS  Google Scholar 

  2. American Psychiatric Association (1994) Diagnostic and statistical manual for mental disorders, 4th ed. American Psychiatric Association, Washington, DC

    Google Scholar 

  3. Almond BW, Tranner JL, Goffman HG (1999) The family is the patient: using family interviews in children’s medical care, 2nd ed. Williams & Wilkins, Baltimore, MD

    Google Scholar 

  4. Schachar R, Taylor E, Wieselberg M, Thorley G, Rutter M (1987) Changes in family function and relationships in children who respond to methylphenidate. J Am Acad Child Adolesc Psychiatry 26(5):728–732

    Article  PubMed  CAS  Google Scholar 

  5. Zentall SS (1993) Research on the educational implications of Attention deficit hyperactivity disorder. Exceptional Children 60(2):143–153

    Google Scholar 

  6. Cutting LE, Koth CW, Mahone EM, Denckla MB (2003) Evidence for unexpected weaknesses in learning in children with attention-deficit/hyperactivity disorder without reading disabilities. J Learning Disabilities 36(3):257–267

    Google Scholar 

  7. Faraone S-V, Biederman J, Monuteaux MCl, Doyle AE, Seidman LJ (2001) A psychometric measure of learning disability predicts educational failure four years later in boys with attention-deficit hyperactivity disorder. J Attention Disorders 4(4):220–230

    Google Scholar 

  8. Maynard J, Tyler JL, Arnold M (1999) Co-occurrence of attention-deficit disorder and learning disability: an overview of research. J Instruct Psychol 26(3):183–187

    Google Scholar 

  9. DuPaul GJ, McGoey KE, Eckert TL, VanBrakle J (2001) Preschool children with attention-deficit/hyperactivity disorder: impairments in behavioral, social, and school functioning. J Am Acad Child Adolesc Psychiatry 40:508–515

    Article  PubMed  CAS  Google Scholar 

  10. Nixon E (2001) The social competence of children with attention deficit hyperactivity disorder: a review of the literature. Child Adolesc Mental Health 6(4):172–180

    Article  Google Scholar 

  11. Thurber JR, Heller TL, Hinshaw SP (2002) The social behaviors and peer expectations of girls with attention deficit hyperactivity disorder and comparison girls. J Clinical Child Adolesc Psychol 31(4):443–452

    Article  Google Scholar 

  12. Biederman J, Faraone SV, Spencer T, Wilens T, Norma D, Lapey KA, Mick E, Krifcher Leham B, Doyle A (1993) Patterns of psychiatric comorbidity, cognition, and psychosocial functioning in adults with Attention deficit hyperactivity disorder. Am J Psychiatry 150:1792–1798

    PubMed  CAS  Google Scholar 

  13. Biederman J, Faraone S, Milberger S, Curtis S, Chen L, Marris A, Ouellette C, Moore P, Spencer T (1996) Predictors of persistence and remissions of ADHD into adolescence: results from a four-year prospective follow-up study. J Am Acad Child Adolesc Psychiatry 35:343–357

    Article  PubMed  CAS  Google Scholar 

  14. Mannuzza S, Klein RG, Bessler A, Malloy P, LaPadula M (1998) Adult psychiatric status of hyperactive boys grown up. Am J Psychiatry 155:493–498

    PubMed  CAS  Google Scholar 

  15. Zametkin AJ, Ernst M (1999) Problems in the management of attention-deficit-hyperactivity disorder. New England J Med 340:40–46

    Article  CAS  Google Scholar 

  16. Swanson J, Kinsbourne M, Roberts W, Zucker K (1978) Time-response analysis of the effect of stimulant medication on the learning ability of children referred for hyperactivity. Pediatrics 61(1):21–29

    PubMed  CAS  Google Scholar 

  17. National Institute of Health (2000) National Institutes of Health consensus development conference statement: diagnosis and treatment of attention-deficit/hyperactivity disorder (ADHD). J Am Acad Child Adolesc Psychiatry 39:182–197

    Google Scholar 

  18. Swanson J (2003) Compliance with stimulants for attention-deficit/hyperactivity disorder. CNS Drugs 17(2):117–131

    Article  PubMed  Google Scholar 

  19. Fitzpatrick PA, Klorman R, Brumaghim JT, Borgstedt AD (1992) Effects of sustained-release and standard preparations of methylphenidate on attention deficit disorder. J Am Acad Child Adolesc Psychiatry 31:226–234

    Article  PubMed  CAS  Google Scholar 

  20. Pelham WE, Greenslade KE, Vodde-Hamilton M, Murphy DA, Greenstein MS, Gnagy EM, Guthrie KJ, Hoover MD, Dahl RE (1990) Relative efficacy of long-acting stimulants on children with Attention deficit-hyperactivity disorder: a comparison of standard methylphenidate, sustained-release methylphenidate, sustained-release dextroamphetamine, and pemoline. Pediatrics 86:226–237

    PubMed  Google Scholar 

  21. Pelham WE, Sturges J, Hoza J, Schmidt C, Bijlsma JJ, Milich R, Moorer S (1987) Sustained-release and standard methylphenidate effects on cognitive and social behavior in children with Attention-deficit disorder. Pediatrics 80:491–501

    PubMed  Google Scholar 

  22. Greenhill LL, Findling RL, Swanson JM, the MPH MR ADHD Study Group (2002) A double-blind, placebo-controlled study of modified-release methylphenidate in children with Attention-Deficit/Hyperactivity Disorder. Pediatrics 109(3)

  23. Hirshey-Dirksen SJ, D’Imperio JM, Birdsall D, Hatch SJ (2002) A postmarketing clinical experience study of Metadate® CD. Curr Med Res Opinions 19(7):371–380

    Article  Google Scholar 

  24. Wigal SB, Sanchez DY, DeCory HH, D’Imperio JM, Swanson JM (2003) Selection of the optimal dose ratio for a controlled-delivery formulation of methylphenidate. J Appl Res 3:46–63

    CAS  Google Scholar 

  25. Kaufman J, Birmaher B, Brent D, Rao U, Flynn C, Moreci P, Williamson D, Ryan N (1997) Schedule for affective disorders and schizophrenia for school-age children-present and lifetime version (K-SADS-PL): initial reliability and validity data. J Am Acad Child Adolesc Psychiatry 36(7):980–988

    Article  PubMed  CAS  Google Scholar 

  26. Loney J, Milich R (1982) Hyperactivity, inattention, and aggression in clinical practice. In: Wolraich M, Routh DK (eds) Advances in development and behavioral pediatrics. JAI Press, Greenwich, CT, pp 113–147

    Google Scholar 

  27. Swanson J (1992) School based assessments and interventions for ADD students. K.C. Publishing, Irvine, CA

    Google Scholar 

  28. Guy W (1976) ECDEU Assessment manual for psychopharmacology, Revised. National Institute of Mental Health, U.S. Department of Health, Education and Welfare, Rockville, MD (Publ. No. 76-338)

  29. Conners CK, Barkley RA (1985) Rating scales and checklists for child psychopharmacology. Psychopharmacol Bull 21(4):809–843

    PubMed  CAS  Google Scholar 

  30. Barkley RA, McMurray MB, Edelbrock CS, Robbins K (1990) Side effects of methylphenidate in children with attention deficit hyperactivity disorder: a systemic, placebo-controlled evaluation. Pediatrics 86:184–192

    PubMed  CAS  Google Scholar 

  31. Wolraich ML, Greenhill LL, Pelham W, Swanson J, Willens T, Palumbo D, Atkins M, McBurnett K, Bulkstein O, August G, in behalf of the Concerta Study Group (2001) Randomized, controlled trial of OROS methylphenidate once a day in children with Attention-deficit/Hyperactivity Disorder. Pediatrics 108(4):883–892

    Article  PubMed  CAS  Google Scholar 

  32. Marcus SC, Wan GJ, Kemner JE, Olfson M (2005) Continuity of methylphenidate treatment for attention-deficit/hyperactivity disorder. Arch Pediatric Adolesc Med 159(6):572–578

    Article  Google Scholar 

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Acknowledgements

Funding for this study was provided by Celltech Americas, Inc., currently part of UCB. Drs. Hatch and DeCory and Miss Cameron were employees for Celltech at the time of this study. Dr. Findling has received research support, acted as a consultant and/or served on a speaker’s bureau for Abbott, AstraZeneca, Bristol-Myers Squibb, Celltech-Medeva, Forest, GlaxoSmithKline, Johnson & Johnson, Lilly, New River, Novartis, Otsuka, Pfizer, Sanofi-Synthelabo, Shire, Solvay, and Wyeth. Dr. Quinn and claims no competitive interests. Dr. McDowell has consulted for Janssen-Cilag and Lilly.

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Authors and Affiliations

  1. Discovery and Wellness Center for Children, Dept. of Psychiatry , University Hospitals of Cleveland Case Western Reserve University, 11100 Euclid Avenue, Cleveland, OH, 44106-5080, USA

    Robert L. Findling MD

  2. Dept. of Psychiatry, University of Saskatchewan, Saskatoon, SK, Canada

    Declan Quinn MD

  3. Medical and Regulatory Affairs, UCB Pharma, Inc., Rochester, NY, USA

    Simon J. Hatch MD & Heleen H. DeCory PhD

  4. UCB Pharma, Sough, Berkshire, UK

    Sara J. Cameron Msc

  5. Child Development Network, Mater CSB, South Brisbane, QLD, Australia

    Michael McDowell MD

Authors
  1. Robert L. Findling MD
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  2. Declan Quinn MD
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  3. Simon J. Hatch MD
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  4. Sara J. Cameron Msc
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  5. Heleen H. DeCory PhD
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  6. Michael McDowell MD
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Correspondence to Robert L. Findling MD.

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Findling, R.L., Quinn, D., Hatch, S.J. et al. Comparison of the clinical efficacy of twice-daily Ritalin® and once-daily Equasym™ XL with placebo in children with Attention Deficit/Hyperactivity Disorder. Eur Child Adolesc Psychiatry 15, 450–459 (2006). https://doi.org/10.1007/s00787-006-0565-0

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