A new study published in Neuroscience and biobehavioral journals provides the first comprehensive meta-analysis of chronic medication effects on cognitive function in people with attention-deficit/hyperactivity disorder (ADHD). The results suggest that two commonly prescribed medications, methylphenidate and atomoxetine, have comparable long-term beneficial effects on executive functions such as attention, inhibition, reaction time, and working memory, with the most pronounced effects seen in improving attention.
ADHD is a common neurodevelopmental disorder, affecting 4–7% of the population. It is characterized by persistent, age-inappropriate symptoms of inattention, hyperactivity, and impulsivity. These symptoms often extend into adulthood, affecting a variety of cognitive functions, particularly executive functions such as sustained attention, working memory, and inhibitory control. Despite the important role that medications play in managing ADHD symptoms, understanding of the specific cognitive benefits of long-term medication use is limited.
“It is very important to understand whether medications given to children with ADHD have long-term effects on cognitive performance, because this is very relevant to their academic or work performance in adults with ADHD,” said study author Katya Rubia, professor of cognitive neuroscience at King’s College London.
“These medications improve ADHD symptoms, but there are no systematic studies on the long-term effects of these medications on cognitive performance. Many studies and meta-analyses have tested the short-term effects of stimulant medications. However, no meta-analyses have been conducted to specifically assess the long-term effects of these medications on ADHD.”
“For atomoxetine, there are no studies or meta-analyses on the effects on cognitive functions. Finally, we were particularly interested in which of these two typical ADHD drugs is more effective in improving cognitive functions.”
The researchers undertook a systematic review and meta-analysis of studies examining the chronic effects of ADHD medications on cognitive function. They conducted a comprehensive literature search of multiple databases, including PubMed, Embase, Ovid MEDLINE, and PsycINFO, up to June 2023. Inclusion criteria included randomized, double-blind, placebo-controlled studies in children, adolescents, and adults diagnosed with ADHD.
The studies had to include at least 10 participants and assess the impact of the medication over a minimum of three days. The analysis included a total of 28 studies, 18 of which looked at methylphenidate and 7 of which looked at atomoxetine. Methylphenidate is a stimulant that works by increasing levels of certain neurotransmitters, such as dopamine and norepinephrine, in the brain, which helps improve attention and reduce impulsivity and hyperactivity. Atomoxetine, on the other hand, is a non-stimulant medication also used to treat ADHD. It works mainly by inhibiting the reuptake of norepinephrine.
The meta-analysis found that both methylphenidate and atomoxetine significantly improved attention, with medium to large effects. Methylphenidate showed a medium effect (Hedges’ g = 0.59), while atomoxetine had a slightly larger effect (Hedges’ g = 0.64). This finding suggests that both medications are highly effective in helping people with ADHD maintain focus and attention, which are critical areas of impairment in this disorder.
In addition to attention, both medications showed positive effects on inhibition, which is the ability to control impulses and resist distractions. Methylphenidate had a small to medium effect size (Hedges’ g = 0.37), and atomoxetine demonstrated a medium effect size (Hedges’ g = 0.47). These improvements in inhibitory control are crucial for managing ADHD symptoms of impulsivity and hyperactivity.
Reaction time also improved with both drugs, although the effect sizes were smaller: methylphenidate (Hedges’ g = 0.34) and atomoxetine (Hedges’ g = 0.36). These improvements indicate better processing speed and response accuracy.
The study found that methylphenidate significantly improved working memory (Hedges’ g = 0.36), while atomoxetine showed a positive trend but did not reach statistical significance (Hedges’ g = 0.30). This difference may be due to the smaller number of atomoxetine studies included in the analysis. Overall, the meta-analysis highlights that both medications provide significant cognitive benefits, with similar efficacy in improving key executive functions in people with ADHD.
“Both commonly used ADHD medications not only improve ADHD behaviors, but also cognitive function,” Rubia told PsyPost. “This is important because it suggests that they will be useful for improving academic or work performance. Both ADHD medications are equally effective at improving cognitive performance, and stimulants are no better than non-stimulants at doing so.”
Although the meta-analysis provides strong evidence that both methylphenidate and atomoxetine can improve key cognitive functions in people with ADHD, some caveats should be considered, such as the relatively small number of studies on atomoxetine compared with methylphenidate. The meta-analysis was unable to include other stimulant and nonstimulant medications due to insufficient data, leaving a gap in understanding the full effects of ADHD medications on cognition.
“We are trying to understand the long- and short-term effects of ADHD medications on cognition and brain function,” Rubia said. “We are also currently testing the effects of newer approved ADHD medications, such as lisdexamfetamine and guanfacine, on ADHD-related cognition and brain function using fMRI.”
The study, “The effects of chronic administration of stimulant and nonstimulant medications on executive functions in ADHD: a systematic review and meta-analysis,” was authored by Ferdous Isfandnia, Sahid El Masri, Joaquim Radua, and Katya Rubia.