Study: Long-Term ADHD Stimulant & Non-Stimulant Use Improves Executive Function

June 28, 2024

Non-stimulant medication is nearly as effective as stimulant medication at improving executive function in children, adolescents, and adults with ADHD, according to a systematic review and meta-analysis published in May by Neuroscience & Biobehavioral Reviews.¹

Long-term use of stimulant and non-stimulant medications had a similar positive effect on cognition, compared to placebo, for people with ADHD. Although the treatment effect sizes varied slightly in magnitude, a meta-regression analysis found no significant differences in the overall impact on cognition between each type of ADHD drug.

Methylphenidate (stimulant) and atomoxetine (non-stimulant) were the only two medications with multiple studies meeting inclusion criteria for this analysis. Improvements were measured based on four main cognitive domains related to ADHD: attention, inhibition, processing speed, and working memory.

Both methylphenidate and atomoxetine were most effective at improving attention and least effective at improving reaction time. Children and adolescents experienced more improvement than adults in reaction time and attention, whereas the effect size for inhibition was greater in adults, although these findings were not statistically significant.

Stimulants Vs. Non-Stimulants & Their Impact on Executive Function

Methylphenidate is the most common stimulant medication prescribed for the treatment of ADHD, followed by amphetamine, according to data cited by the study authors.² Stimulants work for 70% to 80% of children, adolescents, and adults with ADHD, and are typically recommended as a first-line treatment.³ Common brand names include:

• Methylphenidate: Concerta, Jornay PM, Ritalin, and others
• Amphetamine: Adderall, Dexedrine, Desoxyn, Xelstrym, and others

Non-stimulants generally have lower success rates than stimulants, but they are often a better choice for patients who respond poorly to amphetamine or methylphenidate. Atomoxetine is the most common non-stimulant, followed by guanfacine, clonidine, and viloxazine.⁴ Common brand names include:

• Atomoxetine: Strattera
• Guanfacine: Intuniv
• Clonidine: Kapvay
• Viloxazine: Qelbree

In addition to measuring behavioral symptoms — mainly short attention span, hyperactivity, and impulsivity — the present study highlights the potential for stimulants and non-stimulants to improve executive functioning, too.

“It has been shown that improvements in clinical symptoms are independent of improvements in cognitive functions, with clinical improvements not necessarily improving cognition,” wrote Ferdous Isfandnia, the study’s lead author. “It is hence reassuring to show with meta-analytic findings that both stimulant and non-stimulant medications for ADHD not only improve ADHD symptoms but also key cognitive functions that are typically impaired in ADHD.”

Methylphenidate and atomoxetine improve not only ADHD symptoms but also key cognitive functions that impact academic and occupational outcomes, wrote the study’s authors. A person with ADHD may struggle with tasks that involve organizing, planning, managing time, making decisions, and self-motivating. These deficits overlap with ADHD symptoms and contribute to issues at school, work, and home.

Non-stimulants like atomoxetine may be an effective alternative for some patients with ADHD navigating a nationwide stimulant drug shortage, as reported by the CDC and ADDitude. And they can be combined with stimulants, often at lower doses of each, to increase effectiveness, according to psychiatrist Timothy Wilens, M.D.*

“One of the things we found [in our paper] is that stimulants can help, but they often are not sufficient to manage all executive functioning,” Wilens said in an ADDitude webinar on combination therapy to treat complex ADHD. “We’re starting to see that some of the non-stimulants, like Strattera (atomoxetine) and Qelbree (viloxazine), seem to help. When you mix non-stimulants with stimulants, you can get impact.”

Cognitive behavioral therapy can also help manage cognitive symptoms. “These are largely medicated kids… who are still struggling with executive functioning, which is a very common scenario,” Wilens said. “The response rates for individuals by self-report or parent report were between 50% and 60%. So, pretty good outcomes for kids who had stable medicine regimens but still had a lot of cognitive executive functioning.”

Limitations and Future Research

This is the first meta-analysis to show that atomoxetine significantly improves cognitive functions relevant to ADHD, and to demonstrate that these improvements are comparable to methylphenidate. It’s also the first to specifically focus on the chronic use of ADHD medication. The study extended previous findings on the acute benefits of methylphenidate to long-term use.

A total of 28 studies were included: 20 on stimulant medication and 8 on non-stimulant medication. Most participants were male; consequently, these findings may not apply to the full ADHD population. “Chronic” or “long-term” use referred to anywhere from one to eight weeks. Future studies should consider going beyond eight weeks and include additional medications.

“The findings of our meta-analysis of positive effects of chronic administration of methylphenidate and atomoxetine on cognition are encouraging,” wrote the study authors, “as they may likely have an impact on real-life achievements such as school and academic performance in ADHD, as well as occupational performance and overall quality of life.”

*Always consult your healthcare provider before making changes to your treatment plan.

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