Efficacy of two once-daily methylphenidate formulations compared across dose levels at different times of the day: Preliminary indications from a secondary analysis of the COMACS study data

Sonuga-Barke, Edmund J. S.; Swanson, James M.; Coghill, David; DeCory, Heleen H.; Hatch, Simon J.
January 2004
BMC Psychiatry;2004, Vol. 4, p28
Academic Journal
Background: Methylphenidate (MPH) is commonly prescribed in the treatment of Attention-Deficit/ Hyperactivity Disorder or ADHD. Concerta and Metadate CD are once-daily formulations of MPH using different delivery mechanisms resulting in different pharmacokinetic profiles. A recent study (COMACS) showed that for near-milligram (mg) equivalent daily doses, Metadate CD provides greater symptom control in the morning (1.5 through 4.5 hours post-dose), while Concerta provides greater control in the early evening (12 hours post-dose). Non-inferential comparison of effects for different dose levels of the two formulations suggested that equivalent levels of morning symptom control could be obtained with lower daily doses of Metadate CD than Concerta; the situation being reversed in the evening. The current paper presents a secondary analysis that provides a statistical test of these observations. Method: The COMACS study was a multi-center, double-blind crossover study of Metadate CD, Concerta and placebo with each treatment administered for 1 week. Children were assigned on the basis of their pre-trial dosage to either high (Metadate CD 60 mg; Concerta 54 mg), medium (Metadate CD 40 mg; Concerta 36 mg) or low doses (Metadate CD 20 mg; Concerta 18 mg) of MPH, and attended a laboratory school on the 7th day for assessment at 7 sessions across the day. For the post-hoc comparisons across dose levels presented here, total SKAMP scores with the active treatments (adjusted for placebo response) were analyzed using an analysis of covariance, with a combined measure modeling placebo response across all time period as the covariate. Results: Symptom control from 1.5 through 6.0 hours post-dose was as good with lower doses of Metadate CD (20 and 40 mg) as with higher doses of Concerta (36 and 54 mg, respectively). Lower daily doses of Concerta (18 and 36 mg) and higher doses of Metadate CD (40 and 60 mg, respectively) gave equivalent control at 7.5 and 12 hours with Metadate CD giving better control from 1.5 through 6.0 hours post-dose. Conclusions: Different delivery profiles of Metadate CD and Concerta can be exploited to limit total daily exposure to MPH while at the same targeting a specific, especially clinically significant, period of the day. These results need to be confirmed in a study in which children are randomly allocated to different dose levels of the two formulations and plasma MPH concentrations are assessed simultaneously.


Related Articles

  • When preschool children have ADHD.  // Archives of Disease in Childhood;May2007, Vol. 92 Issue 5, p464 

    The article comments on the results of the Preschool ADHD Treatment Study, a randomized trial of the efficacy and safety of methylphenidate (MPH) in preschool children. According to the author, the results of the study demonstrate the effectiveness of stimulant medication in the treatment of...

  • A Dose-Ranging Study of Behavioral and Pharmacological Treatment in Social Settings for Children with ADHD. Pelham, William; Burrows-MacLean, Lisa; Gnagy, Elizabeth; Fabiano, Gregory; Coles, Erika; Wymbs, Brian; Chacko, Anil; Walker, Kathryn; Wymbs, Frances; Garefino, Allison; Hoffman, Martin; Waxmonsky, James; Waschbusch, Daniel // Journal of Abnormal Child Psychology;Aug2014, Vol. 42 Issue 6, p1019 

    Placebo and three doses of methylphenidate (MPH) were crossed with 3 levels of behavioral modification (no behavioral modification, NBM; low-intensity behavioral modification, LBM; and high-intensity behavior modification, HBM) in the context of a summer treatment program (STP). Participants...

  • Methylphenidate dose optimization for ADHD treatment: review of safety, efficacy, and clinical necessity. Huss, Michael; Duhan, Praveen; Gandhi, Preetam; Chien-Wei Chen; Spannhuth, Carsten; Kumar, Vinod // Neuropsychiatric Disease & Treatment;Jul2017, Vol. 13, p1741 

    Attention-deficit/hyperactivity disorder (ADHD) is a chronic psychiatric disorder characterized by hyperactivity and/or inattention and is often associated with a substantial impact on psychosocial functioning. Methylphenidate (MPH), a central nervous system stimulant, is commonly used for...

  • Premarket Safety and Efficacy Studies for ADHD Medications in Children. Bourgeois, Florence T.; Kim, Jeong Min; Mandl, Kenneth D. // PLoS ONE;Jul2014, Vol. 9 Issue 7, p1 

    Background: Attention-deficit hyperactivity disorder (ADHD) is a chronic condition and pharmacotherapy is the mainstay of treatment, with a variety of ADHD medications available to patients. However, it is unclear to what extent the long-term safety and efficacy of ADHD drugs have been evaluated...

  • Zinc sulfate as an adjunct to methylphenidate for the treatment of attention deficit hyperactivity disorder in children: A double blind and randomized trial [ISRCTN64132371]. Akhondzadeh, Shahin; Mohammadi, Mohammad-Reza; Khademi, Mojgan // BMC Psychiatry;2004, Vol. 4, p9 

    Background: Attention-deficit hyperactivity disorder is an early-onset, clinically heterogenous disorder of inattention, hyperactivity, and impulsiveness. The diagnosis and treatment of attention-deficit hyperactivity disorder continues to raise controversy, and, there is also an increase in...

  • Beyond Ritalin. Metten, Ann-Marie // Alive: Canada's Natural Health & Wellness Magazine;Apr2007, Issue 294, p64 

    The article provides information on the use of neurotherapy or biofeedback in children with attention deficit hyperactivity disorder (ADHD). Neurotherapy teaches ADHD children to monitor brain waves through electroencephalogram (EEG) feedback. In a study where ADHD patients took ritalin and used...

  • FDA alert on Ritalin.  // American Family Physician;4/1/1996, Vol. 53 Issue 5, p1890 

    Focuses on an alert issued by the Food and Drug Administration in the United States on the potential of Ritalin to cause cancer. Use of Ritalin for hyperactive children; Basis for FDA's alert; Experiments with mice.

  • Behavior Drugs & Children: An Overview. Bailey, Ellen; Carson-Dewitt, Rosalyn // Points of View: Behavior Drugs & Children;9/30/2019, p1 

    The article presents an overview of the use of behavior drugs in treating children with behavior problems in the U.S. It is noted that based on statistics, suicide due to depression is the third leading cause of death among people aged 15 to 24 in spite of the use of antidepressants and...

  • Initiation and Persistence of Pharmacotherapy for Youths with Attention Deficit Hyperactivity Disorder in Taiwan. Wang, Liang-Jen; Yang, Kang-Chung; Lee, Sheng-Yu; Yang, Chun-Ju; Huang, Ting-Shuo; Lee, Tung-Liang; Yuan, Shin-Sheng; Shyu, Yu-Chiau // PLoS ONE;8/12/2016, Vol. 11 Issue 8, p1 

    Background: Pharmacotherapy is an effective therapeutic option for attention deficit hyperactivity disorder (ADHD). Understanding the patterns of medication treatment is crucial for clinical practice. This study employed nationwide population-based data to elucidate the initiation and...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics