Effects of methylphenidate, desipramine, and L-dopa on attention and inhibition in children with Attention Deficit Hyperactivity Disorder.
The objective of this study was to investigate the effects of methylphenidate (MPH) on attention and inhibition in children with Attention Deficit Hyperactivity Disorder (ADHD) and to establish what the relative contributions of the noradrenergic and dopaminergic systems to this effect were. In addition to MPH, two other drugs were administered in order to affect both transmitter systems more selectively, L-dopa (dopamine (DA) agonist) and desipramine (DMI) (noradrenaline (NA) re-uptake inhibitor). Sixteen children with ADHD performed a stop-task, a laboratory task that measures the ability to inhibit an ongoing action, in a double-blind randomized within-subjects design. Each child received an acute clinical dose of MPH, DMI, L-dopa, and placebo; measures of performance and plasma were determined. The results indicated that inhibition performance was improved under DMI but not under MPH or L-dopa. The response-time to the stop-signal was marginally shortened after intake of DMI. MPH decreased omission and choice-errors and caused faster reaction times to the trials without the stop-tone. No effects of L-dopa whatsoever were noted. Prolactin levels were increased and 5-HIAA levels were lowered under DMI relative to placebo. It is suggested that the effects of MPH on attention are due to a combination of noradrenergic and dopaminergic mechanisms. The improved inhibition under DMI could be serotonergically mediated.
Overtoom
C C E
CC
Department of Psychopharmacology, Faculty of Pharmacy, Utrecht University, P.O. Box 80082, 3508 TB, Utrecht, The Netherlands. C.C.E.Overtoom@pharm.uu.nl
Verbaten
M N
MN
Kemner
C
C
Kenemans
J L
JL
van Engeland
H
H
Buitelaar
J K
JK
van der Molen
M W
MW
van der Gugten
J
J
Westenberg
H
H
Maes
R A A
RA
Koelega
H S
HS
D001288:Attention / Q000187:drug effects*; D001289:Attention Deficit Disorder with Hyperactivity / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D002648:Child; D002755:Choice Behavior / Q000187:drug effects; D003891:Desipramine / Q000031:analogs & derivatives / Q000097:blood / Q000627:therapeutic use*; D015259:Dopamine Agents / Q000627:therapeutic use*; D004311:Double-Blind Method; D004791:Enzyme Inhibitors / Q000097:blood / Q000627:therapeutic use*; D006801:Humans; D006897:Hydroxyindoleacetic Acid / Q000097:blood; D007266:Inhibition, Psychological; D007980:Levodopa / Q000627:therapeutic use*; D008297:Male; D008774:Methylphenidate / Q000627:therapeutic use*; D011388:Prolactin / Q000097:blood; D011930:Reaction Time / Q000187:drug effects
D015259:Dopamine Agents; D004791:Enzyme Inhibitors; D008774:Methylphenidate; D007980:Levodopa; D006897:Hydroxyindoleacetic Acid; D011388:Prolactin; D003891:Desipramine