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July 2, 2025
Most preschool-aged children diagnosed with ADHD also exhibit comorbid mental or developmental conditions. Long-term studies following these children into adulthood have demonstrated that higher severity of ADHD symptoms in early childhood is associated with a more persistent course of ADHD.
The Study:
Sweden has a single-payer national health insurance system that covers virtually all residents, facilitating nationwide population studies. An international study team (US, Brazil, Sweden) searched national registers for predictors of ADHD diagnoses among all 631,695 surviving and non-emigrating preschoolers born from 2001 through 2007.
Preschool ADHD was defined by diagnosis or prescription of ADHD medications issued to toddlers aged three through five years old.
Predictors were conditions diagnosed prior to the ADHD diagnosis.
A total of 1,686 (2.7%) preschoolers were diagnosed with ADHD, with the mean age at diagnosis being 4.6 years.
The Numbers:
Adjusting for sex and birth year, the team reported the following predictors, in order of magnitude:
The Conclusion:
This large population study underscores that many conditions present in early childhood can help predict an ADHD diagnosis in preschoolers. Recognizing these risk factors early may aid in identifying and addressing ADHD sooner, hopefully improving outcomes for children as they grow
Wagner Gurgel, Miguel Garcia-Argibay, Brian M. D’Onofrio, Henrik Larsson, and Guilherme V. Polanczyk, “Predictors of preschool attention-deficit/hyperactivity disorder diagnosis: a population-based study using national registers,” Journal of Child Psychology and Psychiatry (2025), 66:6, 834-845, https://doi.org/10.1111/jcpp.14093.
Parents and teachers often ask: Does ADHD medication actually improve grades and school performance? The answer is: yes, but with important limitations. Medications are very effective at reducing inattention, hyperactivity, and impulsivity but their impact on long-term academic outcomes like grades and test scores is not as consistent.
In the Classroom
The medications for ADHD consistently: Improve attention, reduce classroom disruptions, increase time spent on-task and help children complete more schoolwork and homework. Medication can help children with ADHD access learning by improving the conditions for paying attention and persisting with work.
Does Medication Improve Test Scores and Grades?
This is where the picture gets more complicated. Medications have stronger effect on how much work is completed but a weaker effect on accuracy. Many studies show that children on medication attempt more problems in reading, math, and spelling, but the number of correct answers doesn’t always improve as much. Some studies find small but significant improvements in national exam scores and higher education entrance tests during periods when children with ADHD are medicated.
Grades improve, as well, but modestly. Large registry studies in Sweden show that students who consistently take medication earn higher grades than those who don’t. However, these gains usually do not close the achievement gap with peers who do not have ADHD.
Keep in mind that small improvements for a group as a whole mean that some children are benefiting greatly from medication and others not at all. We have no way of predicting which children will improve and which do not.
Medication Alone Isn’t Enough
Academic success depends on more than just reducing inattention, hyperactivity and impulsivity. Skills like organization, planning, studying, and managing long-term projects are also critical. Medication cannot teach these skills.
So, in addition to medication, the patient's treatment program should include educational support (tutoring, structured study skills programs), behavioral interventions (parent training, classroom management strategies), and accommodations at school (extra time, reduced distractions, organizational aids) Parents should discuss with their prescriber which of these methods would be appropriate.
Conclusions
ADHD medication is a powerful tool for reducing symptoms and supporting learning. It improves test scores and grades for some children, especially when taken consistently. But it is not a magic bullet for academic success. The best results come when medication is combined with educational and behavioral supports that help children build the skills they need to thrive in school and beyond.
In December 2016, the U.S. Food and Drug Administration (FDA) warned “that repeated or lengthy use of general anesthetic and sedation drugs during surgeries or procedures in children younger than 3 years or in pregnant women during their third trimester may affect the development of children’s brains.” The FDA adds, “Health care professionals should balance the benefits of appropriate anesthesia against the potential risks, especially for procedures lasting longer than 3 hours or if multiple procedures are required in children under 3 years,” and “Studies in pregnant and young animals have shown that using these drugs for more than 3 hours caused widespread loss of brain nerve cells.”
That raises a concern that such exposure could lead to increased risk of psychiatric disorders, including ADHD.
Noting “There are inconsistent reports regarding the association between general anesthesia and adverse neurodevelopmental and behavioral disorders in children,” a South Korean study team conducted a nationwide population study to explore possible associations through the country’s single-payer health insurance database that covers roughly 97% of all residents.
The team looked at the cohort of all children born in Korea between 2008 and 2009, and followed them until December 31, 2017. They identified 93,717 children in this cohort who during surgery received general anesthesia with endotracheal intubation (a tube inserted down the trachea), and matched them with an equal number of children who were not exposed to general anesthesia.
The team matched the unexposed group with the exposed group by age, sex, birth weight, residential area at birth, and economic status.
They then assessed both groups for subsequent diagnoses of ADHD.
In general, children exposed to general anesthesia were found to have a 40% greater risk of subsequently being diagnosed with ADHD than their unexposed peers.
This effect was found to be dose dependent by several measures:
All three measures were highly significant.
The authors concluded, “exposure to general anesthesia with ETI [endotracheal intubation] in children is associated with an increased risk of ADHD … We must recognize the possible neurodevelopmental risk resulting from general anesthesia exposure, inform patients and parents regarding this risk, and emphasize the importance of close monitoring of mental health. However, the risk from anesthesia exposure is not superior to the importance of medical procedures. Specific research is needed for the development of safer anesthetic drugs and doses.”
A German team of researchers performed a comprehensive search of the medical literature and identified 35randomized controlled trials (RCTs) published in English that explored this question. Participating children were between three and six years old. Children with intellectual disabilities, sensory disabilities, or specific neurological disorders such as epilepsy were excluded.
The total number of participating preschoolers was over three thousand, drawn almost exclusively from the general population, meaning these studies were not specifically evaluating effects on children with ADHD. But given that ADHD results in poorer executive functioning, evidence of the effectiveness of cognitive training would suggest it could help partially reverse such deficits.
RCTs assign participants randomly to a treatment group and a group not receiving treatment but often receiving a placebo. But RCTs themselves vary in risk of bias, depending on:
After evaluating the RCTs by these criteria, the team performed a series of meta-analyses.
Combining the 23 RCTs with over 2,000 children that measured working memory, they found that cognitive training led to robust moderate improvements. Looking only at the eleven most rigorously controlled studies strengthened the effect, with moderate-to-large gains.
Twenty-six RCTs with over 2,200 children assessed inhibitory control. When pooled, they indicated a small-to-moderate improvement from cognitive training. Including only the seven most rigorously controlled studies again strengthened the effect, boosting it into the moderate effect zone.
Twelve RCTs with over 1,500 participants tested the effects of cognitive training on flexibility. When combined, they pointed to moderate gains. Looking at only the four well-controlled studies boosted the effect to strong gains. Yet here there was evidence of publication bias, so no firm conclusion can be drawn.
Only four studies with a combined total of 119 preschoolers tested the effects on ADHD ratings. The meta-analysis found a small but non-significant improvement, very likely due to insufficient sampling. As the authors noted, "some findings of the meta-analysis are limited by the insufficient number of eligible studies. Specifically, more studies are needed which use blinded assessments of subjective ratings of ADHD ... symptoms ..."
The authors concluded that their meta-analyses revealed significant, mostly medium-sized effects of the preschool interventions on core EFs [executive functions] in studies showing the low risk of bias."
Stimulant medications have long been considered the default first-line treatment for attention-deficit/hyperactivity disorder (ADHD). Clinical guidelines, prescribing practices, and public narratives all reinforce the idea that stimulants should be tried first, with non-stimulants reserved for cases where stimulants fail or are poorly tolerated.
I recently partnered with leading ADHD researcher Jeffrey Newcorn for a Nature Mental Health commentary on the subject. We argue that this hierarchy deserves reexamination. It is important to note that our position is not anti-stimulant. Rather, we call into question whether the evidence truly supports treating non-stimulants as secondary options, and we propose that both classes should be considered equal first-line treatments.
Stimulants have earned their reputation as the go-to drug of choice for ADHD. They are among the most effective medications in psychiatry, reliably reducing core ADHD symptoms and improving daily functioning when properly titrated and monitored. However, when stimulant and non-stimulant medications are compared more closely, the gap between them appears smaller than commonly assumed.
Meta-analyses often report slightly higher average response rates for stimulants, but head-to-head trials where patients are directly randomized to one medication versus another frequently find no statistically significant differences in symptom improvement or tolerability. Network meta-analyses similarly show that while some stimulant formulations have modest advantages, these differences are small and inconsistent, particularly in adults.
When translated into clinical terms, the advantage of stimulants becomes even more modest. Based on existing data, approximately eight patients would need to be treated with a stimulant rather than a non-stimulant for one additional person to experience a meaningful benefit. This corresponds to only a 56% probability that a given patient will respond better to a stimulant than to a non-stimulant. This difference is not what we would refer to as “clinically significant.”
One reason non-stimulants may appear less effective is the way efficacy is typically reported. Most comparisons rely on standardized mean differences, a method of averages that may mask heterogeneity of treatment effects. In reality, ADHD medications do not work uniformly across patients.
For example, evidence suggests that response to some non-stimulants, such as atomoxetine, is bimodal: this means that many patients respond extremely well, while others respond poorly, with few in between. When this happens, average effect sizes can obscure the fact that a substantial subgroup benefits just as much as they would from a stimulant. In other words, non-stimulants are not necessarily less effective across the board, but that they are simply different in who they help.
In our commentary, we also highlight structural issues in ADHD research. Stimulant trials are particularly vulnerable to unblinding, as their immediate and observable physiological effects can reveal treatment assignment, potentially inflating perceived efficacy. Non-stimulants, with slower onset and subtler effects, are less prone to this bias.
Additionally, many randomized trials exclude patients with common psychiatric comorbidities such as anxiety, depression, or substance-use disorders. Using co-diagnoses as exclusion criteria for clinical trials on ADHD medications is nonviable when considering the large number of ADHD patients who also have other diagnoses. Real-world data suggest that a large proportion of individuals with ADHD would not qualify for typical trials, limiting how well results generalize to everyday clinical practice.
Standard evaluations of medication tolerability focus on side effects experienced by patients, but this narrow lens misses broader societal consequences. Stimulants are Schedule II controlled substances, which introduces logistical barriers, regulatory burdens, supply vulnerabilities, and administrative strain for both patients and clinicians.
When used as directed, stimulant medications do not increase risk of substance-use disorders (and, in fact, tend to reduce these rates); however, as ADHD awareness has spread and stimulants are more widely prescribed, non-medical use of prescription stimulants has become more widespread, particularly among adolescents and young adults. Non-stimulants do not carry these risks.
Non-stimulants are not without drawbacks themselves, however. They typically take longer to work and have higher non-response rates, making them less suitable in situations where rapid results are essential. These limitations, however, do not justify relegating them to second-line status across the board.
This is a call for abandoning a one-size-fits-all approach. Instead, future guidelines should present stimulant and non-stimulant medications as equally valid starting points, clearly outlining trade-offs related to onset, efficacy, misuse risk, and practical burden.
The evidence already supports this shift. The remaining challenge is aligning clinical practice and policy with what the data, and patient-centered care, are increasingly telling us.
Today, most treatment guidelines recommend starting ADHD treatment with stimulant medications. These medicines often work quickly and can be very effective, but they do not help every child, and they can have bothersome side effects, such as appetite loss, sleep problems, or mood changes. Families also worry about long-term effects, the possibility of misuse or abuse, as well as the recent nationwide stimulant shortages. Non-stimulant medications are available, but they are usually used only after stimulants have not been effective.
This stimulant-first approach means that many patients who would respond well to a non-stimulant will end up on a stimulant medication anyway. This study addresses this issue by testing two different ways of starting medication treatment for school-age children with attention-deficit/hyperactivity disorder (ADHD). We want to know whether beginning with a non-stimulant medicine can work as well as the “stimulant-first” approach, which is currently used by most prescribers.
From this study, we hope to learn:
Our goal is to give families and clinicians clear, practical evidence to support a truly shared decision: “Given this specific child, should we start with a stimulant or a non-stimulant?”
Who will be in the study?
We will enroll about 1,000 children and adolescents, ages 6 to 16, who:
We will include children with common co-occurring conditions (such as anxiety, depression, learning or developmental disorders) so that the results reflect the “real-world” children seen in clinics, not just highly selected research volunteers.
How will the treatments be assigned?
This is a randomized comparative effectiveness trial, which means:
Parents and clinicians will know which type of medicine the child is taking, as in usual care. However, the experts who rate how much each child has improved using our main outcome measure will not be told which treatment strategy the child received. This helps keep their ratings unbiased.
What will participants be asked to do?
Each family will be followed for 12 months. We will collect information at:
At these times:
We will also track:
Data will be entered into a secure, HIPAA-compliant research database. Study staff at each site will work closely with families to make participation as convenient as possible, including offering flexible visit schedules and electronic options for completing forms when feasible.
How will we analyze the results?
Using standard statistical methods, we will:
All analyses will follow the “intention-to-treat” principle, meaning we compare children based on the strategy they were originally assigned to, even if their medication is later changed. This mirrors real-world decision-making: once you choose a starting strategy, what tends to happen over time?
Why is this study necessary now?
This study addresses a critical, timely gap in ADHD care:
In short, this study is needed now to move ADHD medication decisions beyond “one-size-fits-all.” By rigorously comparing stimulant-first and non-stimulant-first strategies in real-world settings, and by focusing on what matters most to children and families overall functioning, side effects, and long-term well-being, we aim to give patients, parents, and clinicians the information they need to choose the best starting treatment for each child.
This project was conceived by Professor Stephen V. Faraone, PhD (SUNY Upstate Medical University, Department of Psychiatry, Syracuse, NY) and Professor Jeffrey H. Newcorn, MD (Icahn School of Medicine at Mount Sinai, Department of Psychiatry, New York, NY). It will be conducted at nine sites across the USA.
EBI-ADHD:
If you live with ADHD, treat ADHD, or write about ADHD, you’ve probably run into the same problem: there’s a ton of research on treatments, but it’s scattered across hundreds of papers that don’t talk to each other. The EBI-ADHD website fixes that.
EBI-ADHD (Evidence-Based Interventions for ADHD) is a free, interactive platform that pulls together the best available research on how ADHD treatments work and how safe they are. It’s built for clinicians, people with ADHD and their families, and guideline developers who need clear, comparable information rather than a pile of PDFs. EBI-ADHD Database The site is powered by 200+ meta-analyses covering 50,000+ participants and more than 30 different interventions. These include medications, psychological therapies, brain-stimulation approaches, and lifestyle or “complementary” options.
The heart of the site is an interactive dashboard. You can:
The dashboard then shows an evidence matrix: a table where each cell is a specific treatment–outcome–time-point combination. Each cell tells you two things at a glance:
Clicking a cell opens more detail: effect sizes, the underlying meta-analysis, and how the certainty rating was decided.
EBI-ADHD is not just a curated list of papers. It’s built on a formal umbrella review of ADHD interventions, published in The BMJ in 2025. That review re-analyzed 221 meta-analyses using a standardized statistical pipeline and rating system.
The platform was co-created with 100+ clinicians and 100+ people with lived ADHD experience from around 30 countries and follows the broader U-REACH framework for turning complex evidence into accessible digital tools.
Why it Matters
ADHD is one of the most studied conditions in mental health, yet decisions in everyday practice are still often driven by habit, marketing, or selective reading of the literature. EBI-ADHD offers something different: a transparent, continuously updated map of what we actually know about ADHD treatments and how sure we are about it.
In short, it’s a tool to move conversations about ADHD care from “I heard this works” to “Here’s what the best current evidence shows, and let’s decide together what matters most for you.”
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