A Comparison of Once-Daily Extended-Release Methylphenidate Formulations in Children With Attention-Deficit/Hyperactivity Disorder in the Laboratory School (The Comacs Study)
Abstract
Objective The objective of this study was to evaluate differences in the pharmacodynamic (PD) profile of 2 second-generation extended-release (ER) formulations of methylphenidate (MPH): Metadate CD (MCD; methylphenidate HCl, US Pharmacopeia) extended-release capsules, CII, and Concerta (CON; methylphenidate HCl) extended-release tablets, CII. Little empirical information exists to help the clinician compare the PD effects of the available ER formulations on attention and behavior. Previous studies have shown that the near-equal doses of MCD and CON provide equivalent, total exposure to MPH as measured by area under the plasma concentration time curve, yet their pharmacokinetic (PK) plasma concentration versus time profiles are different. We previously offered a theoretical PK/PD account of the similarities and differences among available ER formulations based on the hypothesis that all formulations produce effects related to MPH delivered by 2 processes: 1) an initial bolus dose of immediate-release (IR) MPH that is expected to achieve peak plasma concentration in the early morning and have rapid onset of efficacy within 2 hours of dosing, which for the MCD capsule is delivered by 30% of the total daily dose as uncoated beads and for the CON tablet is delivered by an overcoat of 22% of the total daily dose; and 2) an extended, controlled delivery of ER MPH that is expected to achieve peak plasma concentrations in the afternoon to maintain efficacy for a programmed period of t…
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These common AEs are consistently seen in studies of long-acting stimulant medications administered to adults.
“The common AEs in the current study, including decreased appetite, dry mouth, headache, and insomnia, are consistently seen in studies of long-acting stimulant medications administered to adults [12,18,35,36].”
These findings support and extend previous findings that LDX reduced the symptoms and severity of ADHD compared with placebo in adults in a 4-week controlled trial.
“These findings support and extend previous findings that LDX reduced the symptoms and severity of ADHD compared with placebo in adults in a 4-week controlled trial [18] with measures assessed at weekly intervals (eg, CGI-I ratings and ADHD-RS-IV with adult prompts scores).”
The effects seen in the current study on weight and cardiovascular parameters were consistent with those previously reported for stimulants, including LDX, in adults.
“The effects seen in the current study on weight and cardiovascular parameters were consistent with those previously reported for stimulants, including LDX, in adults [7-9,18,37].”
In a 4-week randomized, forced-dose escalation, double-blind, placebo-controlled study in adults with ADHD, LDX significantly reduced ADHD symptoms compared with placebo at each dose and at each weekly assessment beginning at week 1 through study endpoint.
“These findings support and extend previous findings that LDX reduced the symptoms and severity of ADHD compared with placebo in adults in a 4-week controlled trial [18] with measures assessed at weekly intervals (eg, CGI-I ratings and ADHD-RS-IV with adult prompts scores).”
LDX administration in the current study was associated with modest effects on cardiovascular parameters of blood pressure and pulse.
“As previously seen for LDX in adult patients with ADHD [18], LDX administration in the current study was associated with modest effects on cardiovascular parameters of blood pressure and pulse.”
Exacerbation of morning symptoms has been observed in classroom studies of morning-administered stimulants, where treated children have worse behavior than placebo-treated children in the early morning before their medication is administered.
“Exacerbation of morning symptoms has been observed in classroom studies of morning-administered stimulants, where treated children have worse behavior than placebo-treated children in the early morning before their medication is administered (Swanson et al., 2004).”
From A Post-Hoc Analysis of Emotional Lability With Delayed-Release/Extended-Release Methylphenidate in Children Aged 6 to 12 Years of Age Participating in Two Phase 3 Clinical Trials (2024) · cites this paper as Swanson et al., 2004
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References 30 · Cited by 238
- Authors
- Swanson, J. M., Wigal, S. B., Wigal, T., Sonuga-Barke, E., Greenhill, L. L., Biederman, J., Kollins, S., Nguyen, A. S., DeCory, H. H., Hirshe Dirksen, S. J., Hatch, S. J., & the COMACS Study Group
- Affiliations
- University of California, Irvine (US)
- New York State Psychiatric Institute (US)
- Massachusetts General Hospital (US)
- Duke Medical Center (US)
- Celltech Americas, Inc, Rochester, New York
- ORCID
- Venue
- Pediatrics
- Publisher
- American Academy of Pediatrics (AAP)
- Published
- 2004-03-01
- Volume
- 113
- Issue
- 3
- Pages
- e206-e216
- ISSN
- 0031-4005 (ISSN-L)
- 1098-4275
- OpenAlex
- W1968752176
- Cited by
- 238
- References
- 30
- Citations by year
- 2025: 5 · 2024: 4 · 2023: 8 · 2022: 2 · 2021: 6 · 2020: 3 · 2019: 5 · 2018: 7 · 2017: 6 · 2016: 11 · 2015: 6 · 2014: 15 · 2013: 11 · 2012: 15
- FWCI
- 11.61
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- PEDIATRICS (publishedVersion)
- PubMed (publishedVersion)
- ePrints Soton (University of Southampton) (submittedVersion)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Attention Deficit Hyperactivity Disorder
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Pharmaceutical studies and practices
- Social Sciences › Psychology › Developmental and Educational Psychology › Behavioral and Psychological Studies
- Keywords
- methylphenidate, sustained-release formulation, Concerta, attention deficit hyperactivity disorder, children, pharmacodynamics, pharmacokinetics, pharmacokinetic-pharmacodynamic modeling, bioequivalence, double-blind crossover, experimental schools, dose comparison
- MeSH terms
- Central Nervous System Stimulants, Attention Deficit Disorder with Hyperactivity, Capsules, Child, Delayed-Action Preparations, Double-Blind Method, Drug Administration Schedule, Female, Humans, Male, Methylphenidate, Tablets, Cross-Over Studies
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