Rate dependency revisited: understanding the effects of methylphenidate in children with attention deficit hyperactivity disorder.
Although stimulants are widely prescribed for the treatment of attention deficit hyperactivity disorder (ADHD), their calming effects are not easily understood. One hypothesis derived from preclinical studies is that stimulants exert "rate-dependent" effects that are inversely related in magnitude and direction to the baseline rate of activity or distraction. Previously, compelling support for this hypothesis has been lacking. We provide preliminary evidence that methylphenidate exerts rate-dependent behavioral effects in children with ADHD. Activity and attention were quantified in children with ADHD tested on placebo and different doses of methylphenidate using objective measures. Higher doses altered activity and attentiveness in a rate-dependent manner after correction for regression-to-the-mean artifacts. These findings illustrate a clear inverse association between symptom severity and degree of therapeutic response that is crucial for our understanding of stimulant effects and effective clinical treatment of ADHD.
Teicher
Martin H
MH
Department of Psychiatry, Harvard Medical School, Boston, MA, USA. martin_teicher@hms.harvard.edu
Polcari
Ann
A
Anderson
Carl M
CM
Andersen
Susan L
SL
Lowen
Steven B
SB
Navalta
Carryl P
CP
D001288:Attention / Q000187:drug effects; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy* / Q000523:psychology; D000697:Central Nervous System Stimulants / Q000009:adverse effects / Q000627:therapeutic use*; D002648:Child; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D008774:Methylphenidate / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
D000697:Central Nervous System Stimulants; D008774:Methylphenidate