Methylphenidate but not atomoxetine or citalopram modulates inhibitory control and response time variability

Response inhibition is a prototypical executive function of considerable clinical relevance to psychiatry. Nevertheless, our understanding of its pharmacological modulation remains incomplete.

We used a randomized, double-blind, placebo-controlled, crossover design to examine the effect of an acute dose of methylphenidate (MPH) (30 mg), atomoxetine (ATM) (60 mg), citalopram (CIT) (30 mg), and placebo (PLAC) (dextrose) on the stop signal inhibition task in 24 healthy, right-handed men 18-35 years of age. Participants performed the task under each of the four drug conditions across four consecutive sessions.

Methylphenidate led to a reduction in both response time variability and stop-signal reaction time (SSRT), indicating enhanced response inhibition compared with all other drug conditions. Crucially, the enhancement of response inhibition by MPH occurred without concomitant changes in overall response speed, arguing against a simple enhancement of processing speed. We found no significant differences between ATM and PLAC, CIT and PLAC, or ATM and CIT for either response time variability or SSRT.

An acute dose of MPH but not ATM or CIT was able to improve SSRT and reduce response time variability in nonclinical participants. Improvements in response inhibition and response variability might underlie the reported clinical benefits of MPH in disorders such as attention-deficit/hyperactivity disorder.