Methylphenidate Restores Link Between Stop-Signal Sensory Impact and Successful Stopping in Adults with Attention-Deficit/Hyperactivity Disorder

• Published in: Biological psychiatry (1969) 2009-04, Vol.65 (7), p.614-619
• Main Authors: Overtoom, Carin C.E, Bekker, Evelijne M, van der Molen, Maurits W, Verbaten, Marinus N, Kooij, J.J. Sandra, Buitelaar, Jan K, Kenemans, J. Leon
• Format: Article
• Language: English
• Subjects: ADHD; Adult; Attention Deficit Disorder with Hyperactivity - drug therapy; Attention Deficit Disorder with Hyperactivity - physiopathology; Attention deficit disorders. Hyperactivity; Biological and medical sciences; Central Nervous System Stimulants - pharmacology; Central Nervous System Stimulants - therapeutic use; Cerebral Cortex - drug effects; Cerebral Cortex - physiopathology; Child clinical studies; Double-Blind Method; Female; Humans; Inhibition (Psychology); Male; Medical sciences; methylphenidate; Methylphenidate - pharmacology; Methylphenidate - therapeutic use; N1 effect; Neuropharmacology; paroxetine; Paroxetine - pharmacology; Paroxetine - therapeutic use; Pharmacology. Drug treatments; Placebos; Psychiatry; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease); Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Psychopharmacology; Reaction Time - drug effects; Serotonin Uptake Inhibitors - pharmacology; Serotonin Uptake Inhibitors - therapeutic use; stop task
• ISSN: 0006-3223; 1873-2402
• DOI: 10.1016/j.biopsych.2008.10.048

Background The ability to revise one's action plans, as reflected in so-called stopping performance, is of fundamental importance to adaptive behavior. Previous studies in children and adults with attention-deficit/hyperactivity disorder (ADHD) have revealed impaired stopping, which improved after the administration of methylphenidate (MPH). Event-related brain potentials revealed that one crucial mechanism in adequate stopping is the link between the cortical areas that process the signal to stop and the motor system (stop N1). This stop N1 was severely compromised in adults with ADHD. The present study investigates whether methylphenidate can restore the stop N1, in addition to improving stopping performance. The acute effect of a serotonergic reuptake inhibition on these parameters was also assessed. Methods Twelve adult combined-type ADHD patients received either placebo, MPH .4 mg/kg or .6 mg/kg, or 20 mg paroxetine in a double-blind, randomized, within-subjects design. Results The .6 mg/kg dose of methylphenidate improved stopping performance, whereas it did not affect go reaction time (RT). It also restored the stop N1 that was absent under placebo. Methylphenidate reduced a later stop-related potential, the stop P3, which may reflect monitoring of failed stops. Paroxetine had no effect on stopping performance or on stop N1, but it reduced stop P3. Conclusions A .6 mg/kg dose of methylphenidate improves stopping performance and directly targets a stop-related brain mechanism that has been reported before to be compromised in a group of ADHD patients. This mechanism was not influenced by acute serotonergic reuptake inhibition.