The Effects of Chronic Administration of Stimulant and Non-stimulant Medications on Executive Functions in ADHD:A Systematic Review and Meta-Analysis

Attention-Deficit/Hyperactivity Disorder (ADHD) is associated with executive function deficits that are improved with medications. However, meta-analyses of stimulant effects on cognition have mostly tested single-dose effects, and there is no meta-analysis of non-stimulant effects. This systematic review and meta-analysis tested the clinically more relevant longer-term effects of Methylphenidate (20 studies; minimum 1 week) and Atomoxetine (8 studies; minimum 3 weeks) on reaction time, attention, inhibition, and working memory, searching papers on PubMed, Embase, Ovid MEDLINE, and PsycINFO. The meta-analysis of 18 studies in 1667 subjects showed that methylphenidate was superior to placebo in all cognitive domains with small to medium effect sizes (Hedges g of 0.34–0.59). The meta-analysis of atomoxetine included 7 studies in 829 subjects and showed no effects in working memory, but superior effects in the other domains with medium to large effect sizes (Hedge's g of 0.36–0.64). Meta-regression analysis showed no drug differences on cognitive effects. The meta-analyses show for the first time that chronic Methylphenidate and Atomoxetine have comparable effects of improving executive functions in people with ADHD.