Efficacy of a new pattern of delivery of methylphenidate for the treatment of ADHD: effects on activity level in the classroom and on the playground.

OBJECTIVES To evaluate the pharmacodynamic effects of an experimental (EXP) delivery of methylphenidate (MPH) in children with attention-deficit/hyperactivity disorder and to investigate the situational nature of effects in laboratory classroom and playground settings. METHOD A "sipping" study methodology was used to deliver a bolus followed by small but increasing MPH doses as the EXP regimen. A randomized, double-blind crossover design was used to compare the EXP regimen to a thrice-daily (TID) regimen and a placebo (PLA) regimen. Measures of efficacy were obtained from a Motionlogger actigraph to quantify activity and from the Swanson, Kotkin, Agler, M-Flynn, and Pelham (SKAMP) rating scale to quantify two domains of behavior (attention and deportment). RESULTS Compared with PLA, both EXP and TID delivery of MPH produced large, significant reductions in activity and inappropriate behavior in the classroom, but the two MPH regimens did not differ in onset or duration of effects across the day. The MPH effects were situationally dependent and were smaller for the playground than for the classroom settings. CONCLUSIONS The findings of this "proof of concept" study support the efficacy of a continuous, ascending delivery of MPH. The situational effects of MPH provide support for the theory of selective effects of stimulants, dependent on the demands of the environment.

[1]  R. E. Hicks,et al.  Neuropharmacology of methylphenidate and a neural substrate for childhood hyperactivity. , 1985, The Psychiatric clinics of North America.

[2]  J. Swanson,et al.  Reliability and validity of the SKAMP rating scale in a laboratory school setting. , 1998, Psychopharmacology bulletin.

[3]  T. Zentall,et al.  Activity and task performance of hyperactive children as a function of environmental stimulation. , 1976, Journal of consulting and clinical psychology.

[4]  Stephen P. Hinshaw,et al.  A 14-month randomized clinical trial of treatment strategies for attention-deficit/hyperactivity disorder. The MTA Cooperative Group. Multimodal Treatment Study of Children with ADHD. , 1999, Archives of general psychiatry.

[5]  J. Swanson,et al.  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. , 2003, Archives of general psychiatry.

[6]  R. Parasuraman The attentive brain , 1998 .

[7]  J. Rapoport,et al.  A naturalistic assessment of the motor activity of hyperactive boys. II. Stimulant drug effects. , 1983, Archives of general psychiatry.

[8]  H. Meltzer,et al.  Psychopharmacology : the third generation of progress , 1987 .

[9]  M. Posner,et al.  Images of mind , 1994 .

[10]  N. Volkow,et al.  Dopamine transporter occupancies in the human brain induced by therapeutic doses of oral methylphenidate. , 1998, The American journal of psychiatry.

[11]  J. Swanson,et al.  Medication treatment strategies in the MTA Study: relevance to clinicians and researchers. , 1996, Journal of the American Academy of Child and Adolescent Psychiatry.

[12]  T. Saxton,et al.  Hyperactivity and delay aversion. III: The effect on cognitive style of imposing delay after errors. , 1996, Journal of child psychology and psychiatry, and allied disciplines.

[13]  J. Swanson,et al.  Moderators and mediators of treatment response for children with attention-deficit/hyperactivity disorder: the Multimodal Treatment Study of children with Attention-deficit/hyperactivity disorder. , 1999, Archives of general psychiatry.

[14]  J. Morton,et al.  Causal modeling: A structural approach to developmental psychopathology. , 1995 .

[15]  R Tannock,et al.  Does actigraphy differentiate ADHD subtypes in a clinical research setting? , 2000, Journal of the American Academy of Child and Adolescent Psychiatry.

[16]  I. Shoulson,et al.  Acute tolerance to methylphenidate in the treatment of attention deficit hyperactivity disorder in children , 1999, Clinical pharmacology and therapeutics.

[17]  M. Posner,et al.  Attention-deficit/hyperactivity disorder: Symptom domains, cognitive processes, and neural networks. , 1998 .

[18]  H. Kraemer,et al.  Impairment and deportment responses to different methylphenidate doses in children with ADHD: the MTA titration trial. , 2001, Journal of the American Academy of Child and Adolescent Psychiatry.

[19]  J. Panksepp Affective Neuroscience: The Foundations of Human and Animal Emotions , 1998 .

[20]  Giuseppe Esposito,et al.  Dextroamphetamine Enhances “Neural Network-Specific” Physiological Signals: A Positron-Emission Tomography rCBF Study , 1996, The Journal of Neuroscience.

[21]  M. Posner,et al.  Executive attention: Conflict, target detection, and cognitive control. , 1998 .

[22]  M. Stein,et al.  Methylphenidate dosing: twice daily versus three times daily. , 1996, Pediatrics.

[23]  H. Koplewicz,et al.  Effects of late-afternoon methylphenidate administration on behavior and sleep in attention-deficit hyperactivity disorder. , 1995, Pediatrics.