Abstract
Objectives
To use growth mixture modelling (GMM) to identify subgroups of children with attention deficit hyperactive disorder (ADHD) who have different pharmacodynamic profiles in response to extended release methylphenidate as assessed in a laboratory classroom setting.
Methods
GMM analysis was performed on data from the COMACS study (Comparison of Methylphenidates in the Analog Classroom Setting): a large (n = 184) placebo-controlled cross-over study comparing three treatment conditions in the Laboratory School Protocol (with a 1.5-h cycle of attention and deportment assessments). Two orally administered, once-daily methylphenidate (MPH) bioequivalent formulations [Metadate CD™/Equasym™ XL (MCD-EQXL) and Concerta XL (CON)] were compared with placebo (PLA).
Results
Three classes of children with distinct severity profiles in the PLA condition were identified. For both MCD-EQXL and CON, the more severe their PLA symptoms the better, the children’s response. However, the formulations produced different growth curves by class, with CON having essentially a flat profile for all three classes (i.e. no effect of PLA severity) and MCD-EQXL showing a marked decline in symptoms immediately post-dosing in the two most severe classes compared with the least severe. Comparison of daily doses matched for immediate-release (IR) components accounted for this difference.
Conclusion
The results suggest considerable heterogeneity in the pharmacodynamics of MPH response by children with ADHD. When treatment response for near-equal, bioequivalent daily doses the two formulations was compared, marked differences were seen for children in the most severe classes with a strong curvilinear trajectory for MCD-EQXL related to the greater IR component.
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References
Adesman A (2004) Flawed attention-deficit/hyperactivity disorder mediation comparison. Pediatrics 114:1132
Antrop I, Buysse A, Roeyers H, Van Oost P (2005) Activity in children with ADHD during waiting situations in the classroom: a pilot study. Br J Educ Psychol 75:51–69
Banaschewski T, Coghill D, Santosh P, Zuddas A, Asherson P, Buitelaar J, Danckaerts M, Dopfner M, Faraone SV, Rothenberger A, Sergeant J, Steinhausen HC, Sonuga-Barke EJS, Taylor E (2006) Long-acting medications for the hyperkinetic disorders – a systematic review and European treatment guideline. Eur Child Adolesc Psychiatry 15:476–495
Bentler PM (1990) Comparative fit indexes in structural models. Psychol Bull 107:238–246
Bollen K, Long JS (1993) Testing structural equation models. Sage, Newbury Park
Cohen J (1988) Statistical power analysis for the behavioral sciences, 2nd edn. Erlbaum, Hillsdale
Cuijpers P van Lier PAC, van Straten A, Donker M (2005) Examining differential effects of psychological treatment of depressive disorder: an application of trajectory analyses. J Affect Disord 89:137–146
Gonzalez MA, Pentikis HS, Anderl N, Benedict MF, DeCory HH, Dirksen SJH, Hatch SJ (2002) Methylphenidate bioavailability from two extended-release formulations. Int J Clin Pharmacol Ther 40:175–184
Greenhill LL, Abikoff HB, Arnold LE, Cantwell DP, Conners CK, Elliott G, Hechtman L, Hinshaw SP, Hoza B, Jensen PS, March JS, Newcorn J, Pelham WE, Severe JB, Swanson JM, Bitiello B, Wells K (1996) Medication treatment strategies in the MTA study: relevance to clinicians and researchers. J Am Acad Child Adolesc Psychiatry 35:1304–1313
Hazell P, Lewin T, Sly K (2005) What is a clinically important level of improvement in symptoms of attention-deficit/hyperactivity disorder? Aust NZ J Psychiatry 39:354–358
Kass RE, Raftery AE (1995) Bayes factors. J Am Stat Assoc 90:773–795
Muthén BO, Shedden K (1999) Finite mixture modeling with mixture outcomes using the EM algorithm. Biometrics 55:463–469
Muthén LK, Muthén BO (1998–2006) Mplus user’s guide, 4th edn. Muthén & Muthén Los Angeles
Satorra A (2000) Scaled and adjusted restricted tests in multi-sample analysis of moment structures. In: Heijmans RDH, Pollock DSG, Satorra A (eds) Innovations in multivariate statistical analysis. A Festschrift for Heinz Neudecker. Kluwer Academic Publishers, London, pp 233–247
Sonuga-Barke EJS, Swanson JM, Coghill D, DeCory HH, Hatch SJ (2004) 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. BMC Psychiatry 4:28
Sonuga-Barke EJS, Swanson J, Markowitz J, Coghill D, Vandenberghe M, Hatch S (2007) Sex differences in the pharmacodynamics of ADHD children’s response to methylphenidate: a comparison of two formulations. J Am Acad Child Adolesc Psychiatry 46:701–710
Swanson JM (1992) School based assessments and interventions for ADD students. KC Publishing, Irvine
Swanson JM, Agler D, Fineberg E, Wigal S, Flynn D, Fineberg K, Quintana Y, Talebi H (1999) University of California, Irvine, laboratory school protocol for pharmacokinetic and pharmacodynamic studies. In: Greenhill L, Osman B (eds) Ritalin: theory and practice, 2nd edn. Mary Ann Liebert, Inc. Publishers, New York, pp 405–430
Swanson JM, the COMACS Group (2004) Flawed attention-deficit/hyperactivity disorder mediation comparison: in reply. Pediatrics 114:1132–1133
Swanson J, Gupta S, Lam A, Shoulson I, Lerner M, Modi N, Lindemulder E, Wigal S (2003) Development of a new once-a-day formulation of methylphenidate for the treatment of attention-deficit/hyperactivity disorder proof-of-concept and proof-of-product studies. Arch Gen Psychiatry 60:204–211
Swanson J, Lerner M, Wigal T, Steinhoff K, Greenhill L, Posner K, Freid J, Wigal S (2002) The use of a laboratory school protocol to evaluate concepts about efficacy and side effects of new formulations of stimulant medications. J Atten Disord 6:S73–S88
Swanson JM, Wigal SB, Wigal T, Sonuga-Barke E, Greenhill LL, Biederman J, Kollins S, Nguyen AS, DeCory HH, Dirksen SJH, Hatch SJ, COMACS Study Group (2004) A comparison of once-daily extended-release methylphenidate formulations in children with attention-deficit/hyperactivity disorder in the laboratory school (the COMACS study). Pediatrics 113:E206–E216
Taylor E, Dopfner M, Sergeant J, Asherson P, Banaschewski T, Buitelaar J, Coghill D, Danckaerts M, Rothenberger A, Sonuga-Barke E, Steinhausen HC, Zuddas A (2004) European clinical guidelines for hyperkinetic disorder – first upgrade European clinical guidelines for hyperkinetic disorder – first upgrade. Eur Child Adolesc Psychiatry 13:17–130
van Lier PAC, van der Ende J, Koot HM, Verhulst FC (2007) Which better predicts conduct problems? The relationship of trajectories of conduct problems with ODD and ADHD symptoms form childhood to adolescence. J Child Psychol Psychiatry 48:601–608
Vitiello B, Severe JB, Greenhill LL, Arnold LE, Abikoff HB, Bukstein OG, Elliott GR, Hechtman L, Jensen PS, Hinshaw SP, March JS, Newcorn JH, Swanson JM, Cantwell DP (2001) Methylphenidate dosage for children with ADHD over time under controlled conditions: lessons from the MTA. J Am Acad Child Adolesc Psychiatry 40:188–196
Wigal SB, Wigal TL (2006) The laboratory school protocol: its origin, use, and new applications. J Atten Disord 10:92–111
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Sonuga-Barke, E.J.S., Van Lier, P., Swanson, J.M. et al. Heterogeneity in the pharmacodynamics of two long-acting methylphenidate formulations for children with attention deficit/hyperactivity disorder. Eur Child Adolesc Psychiatry 17, 245–254 (2008). https://doi.org/10.1007/s00787-007-0667-3
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DOI: https://doi.org/10.1007/s00787-007-0667-3