TY - JOUR
T1 - Common and unique therapeutic mechanisms of stimulant and nonstimulant treatments for attention-deficit/hyperactivity disorder
AU - Schulz, Kurt P.
AU - Fan, Jin
AU - Bédard, Anne Claude V.
AU - Clerkin, Suzanne M.
AU - Ivanov, Iliyan
AU - Tang, Cheuk Y.
AU - Halperin, Jeffrey M.
AU - Newcorn, Jeffrey H.
PY - 2012/9
Y1 - 2012/9
N2 - Context: Attention-deficit/hyperactivity disorder (ADHD) is a highly prevalent and impairing psychiatric disorder that affects both children and adults. There are Food and Drug Administration - approved stimulant and nonstimulant medications for treating ADHD; however, little is known about the mechanisms by which these different treatments exert their therapeutic effects. Objective: To contrast changes in brain activation related to symptomatic improvement with use of the stimulant methylphenidate hydrochloride vs the nonstimulant atomoxetine hydrochloride. Design: Functional magnetic resonance imaging before and after 6 to 8 weeks of treatment with methylphenidate (n = 18) or atomoxetine (n = 18) using a parallelgroups design. Setting: Specialized ADHD clinical research program at Mount Sinai School of Medicine, New York, New York. Participants: Thirty-six youth with ADHD (mean [SD] age, 11.2 [2.7] years; 27 boys) recruited from randomized clinical trials. Main Outcome Measures: Changes in brain activation during a go/no-go test of response inhibition and investigator-completed ratings on the ADHD Rating Scale-IV-Parent Version. Results: Treatment with methylphenidate vs atomoxetine was associated with comparable improvements in both response inhibition on the go/no-go test and mean (SD) improvements in ratings of ADHD symptoms (55% [30%] vs 57% [25%]). Improvement in ADHD symptoms was associated with common reductions in bilateral motor cortex activation for both treatments. Symptomatic improvement was also differentially related to gains in task-related activation for atomoxetine and reductions in activation for methylphenidate in the right inferior frontal gyrus, left anterior cingulate/supplementary motor area, and bilateral posterior cingulate cortex. These findings were not attributable to baseline differences in activation. Conclusions: Treatment with methylphenidate and atomoxetine produces symptomatic improvement via both common and divergent neurophysiologic actions in frontoparietal regions that have been implicated in the pathophysiology of ADHD. These results represent a first step in delineating the neurobiological basis of differential response to stimulant and nonstimulant medications for ADHD.
AB - Context: Attention-deficit/hyperactivity disorder (ADHD) is a highly prevalent and impairing psychiatric disorder that affects both children and adults. There are Food and Drug Administration - approved stimulant and nonstimulant medications for treating ADHD; however, little is known about the mechanisms by which these different treatments exert their therapeutic effects. Objective: To contrast changes in brain activation related to symptomatic improvement with use of the stimulant methylphenidate hydrochloride vs the nonstimulant atomoxetine hydrochloride. Design: Functional magnetic resonance imaging before and after 6 to 8 weeks of treatment with methylphenidate (n = 18) or atomoxetine (n = 18) using a parallelgroups design. Setting: Specialized ADHD clinical research program at Mount Sinai School of Medicine, New York, New York. Participants: Thirty-six youth with ADHD (mean [SD] age, 11.2 [2.7] years; 27 boys) recruited from randomized clinical trials. Main Outcome Measures: Changes in brain activation during a go/no-go test of response inhibition and investigator-completed ratings on the ADHD Rating Scale-IV-Parent Version. Results: Treatment with methylphenidate vs atomoxetine was associated with comparable improvements in both response inhibition on the go/no-go test and mean (SD) improvements in ratings of ADHD symptoms (55% [30%] vs 57% [25%]). Improvement in ADHD symptoms was associated with common reductions in bilateral motor cortex activation for both treatments. Symptomatic improvement was also differentially related to gains in task-related activation for atomoxetine and reductions in activation for methylphenidate in the right inferior frontal gyrus, left anterior cingulate/supplementary motor area, and bilateral posterior cingulate cortex. These findings were not attributable to baseline differences in activation. Conclusions: Treatment with methylphenidate and atomoxetine produces symptomatic improvement via both common and divergent neurophysiologic actions in frontoparietal regions that have been implicated in the pathophysiology of ADHD. These results represent a first step in delineating the neurobiological basis of differential response to stimulant and nonstimulant medications for ADHD.
UR - http://www.scopus.com/inward/record.url?scp=84866045828&partnerID=8YFLogxK
U2 - 10.1001/archgenpsychiatry.2011.2053
DO - 10.1001/archgenpsychiatry.2011.2053
M3 - Article
C2 - 22945622
AN - SCOPUS:84866045828
SN - 0003-990X
VL - 69
SP - 952
EP - 961
JO - Archives of General Psychiatry
JF - Archives of General Psychiatry
IS - 9
ER -