Stimulant and non-stimulant ADHD medications equally effective in enhancing cognitive functions

A new study published in Neuroscience and Biobehavioral Reviews provides the first comprehensive meta-analysis of the chronic effects of medications on cognitive functions in people with Attention Deficit/Hyperactivity Disorder (ADHD). The findings suggest that two commonly prescribed medications, methylphenidate and atomoxetine, have comparable long-term benefits on executive functions such as attention, inhibition, reaction time, and working memory, with the most pronounced effects seen in improved attention.

ADHD is a prevalent neurodevelopmental disorder, affecting 4-7% of the population. It is characterized by persistent, age-inappropriate symptoms of inattention, hyperactivity, and impulsiveness. These symptoms often extend into adulthood, impacting various cognitive functions, particularly executive functions like sustained attention, working memory, and inhibitory control. Despite the significant role that medication plays in managing ADHD symptoms, understanding the specific cognitive benefits of long-term medication use has been limited.

“It is very important to understand whether the medications given to ADHD children have longer-term effects on cognitive performance as this is very relevant for their academic performance at school or at their occupation in adults with ADHD,” said study author Katya Rubia, a professor of cognitive neuroscience at King’s College London.

“These medications improve the symptoms of ADHD but there was no systematic review on the longer term effects of these medications on their cognitive performance. There are a lot of studies and meta-analyses that have tested the short term effects of stimulant medication. However, no meta-analyses have been conducted that assess specifically the longer-term effects of these medication in ADHD.’

“For atomoxetine, there is no review or meta-analysis on the effects on cognitive functions. Lastly, we were also particularly interested which of these two typical ADHD medications is better in improving cognitive functions.”

The researchers undertook a systematic review and meta-analysis of studies examining the chronic effects of ADHD medications on cognitive functions. They conducted a comprehensive literature search across multiple databases, including PubMed, Embase, Ovid MEDLINE, and PsycINFO, up until June 2023. The inclusion criteria focused on randomized, double-blind, placebo-controlled studies involving children, adolescents, and adults diagnosed with ADHD.

Studies had to have at least 10 participants and assess the impact of medication over a minimum of three days. The analysis included a total of 28 studies, with 18 examining methylphenidate and 7 examining atomoxetine. Methylphenidate is a stimulant that works by increasing the 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 primarily works by inhibiting the reuptake of norepinephrine.

The meta-analysis revealed that both methylphenidate and atomoxetine significantly improved attention, with medium to large effect sizes. Methylphenidate showed a medium effect size (Hedges’ g = 0.59), while atomoxetine had a slightly larger effect size (Hedges’ g = 0.64). This finding suggests that both medications are highly effective in helping individuals with ADHD maintain focus and sustain attention, which are critical areas of impairment in this disorder.

In addition to attention, both drugs 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 the impulsivity and hyperactivity symptoms of ADHD.

Reaction time also improved with both medications, 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), whereas atomoxetine showed a positive trend but did not reach statistical significance (Hedges’ g = 0.30). This difference might 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 drugs commonly used for ADHD do not just improve ADHD behaviors but also improve cognitive functions,” Rubia told PsyPost. “This is important as it suggests they will be useful to improve school performance or occupational performance. Both ADHD medications are equally good in improving cognitive performance and stimulants are not better than non-stimulants in doing that.”

While the meta-analysis provides robust evidence that both methylphenidate and atomoxetine can improve key cognitive functions in people with ADHD, there are some caveats to consider, such as the relatively small number of studies on atomoxetine compared to methylphenidate. The meta-analysis was unable to include other stimulant and non-stimulant medications due to insufficient data, leaving a gap in understanding the full spectrum of ADHD medication effects on cognition.

“We are trying to understand the longer and shorter term effects of ADHD drugs on cognition, and brain function,” Rubia said. “We are also testing currently the effects of newer licenced drugs for ADHD such as lisdexamfetamine and guanfacine on ADHD cognition and brain function using fMRI.”

The study, “The effects of chronic administration of stimulant and non-stimulant 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.