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January 2, 2026
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.
A Chinese research team performed two types of meta-analyses to compare the risk of suicide for ADHD patients taking ADHD medication as opposed to those not taking medication.
The first type of meta-analysis combined six large population studies with a total of over 4.7 million participants. These were located on three continents - Europe, Asia, and North America - and more specifically Sweden, England, Taiwan, and the United States.
The risk of suicide among those taking medication was found to be about a quarter less than for unmediated individuals, though the results were barely significant at the 95 percent confidence level (p = 0.49, just a sliver below the p = 0.5 cutoff point). There were no significant differences between males and females, except that looking only at males or females reduced sample size and made results non-significant.
Differentiating between patients receiving stimulant and non-stimulant medications produced divergent outcomes. A meta-analysis of four population studies covering almost 900,000 individuals found stimulant medications to be associated with a 28 percent reduced risk of suicide. On the other hand, a meta-analysis of three studies with over 62,000 individuals found no significant difference in suicide risk for non-stimulant medications. The benefit, therefore, seems limited to stimulant medication.
The second type of meta-analysis combined three within-individual studies with over 3.9 million persons in the United States, China, and Sweden. The risk of suicide among those taking medication was found to be almost a third less than for unmediated individuals, though the results were again barely significant at the 95 percent confidence level (p =0.49, just a sliver below the p = 0.5 cutoff point). Once again, there were no significant differences between males and females, except that looking only at males or females reduced the sample size and made results non-significant.
Differentiating between patients receiving stimulant and non-stimulant medications once again produced divergent outcomes. Meta-analysis of the same three studies found a 25 percent reduced risk of suicide among those taking stimulant medications. But as in the population studies, a meta-analysis of two studies with over 3.9 million persons found no reduction in risk among those taking non-stimulant medications.
A further meta-analysis of two studies with 3.9 million persons found no reduction in suicide risk among persons taking ADHD medications for 90 days or less, "revealing the importance of duration and adherence to medication in all individuals prescribed stimulants for ADHD."
The authors concluded, "exposure to non-stimulants is not associated with a higher risk of suicide attempts. However, a lower risk of suicide attempts was observed for stimulant drugs. However, the results must be interpreted with caution due to the evidence of heterogeneity ..."
Noting that “the association between adult ADHD and dementia risk remains a topic of interest because of inconsistent results,” an Israeli study team tracked 109,218 members of a nonprofit Israeli health maintenance organization born between 1933 and 1952 who entered the cohort on January 1, 2003, without an ADHD or dementia diagnosis and were followed up to February 28, 2020.
Israeli law forbids nonprofit HMOs from turning anyone away based on demographic factors, health conditions, or medication needs, thereby limiting sample selection bias.
The estimated prevalence of dementia in this HMO, as diagnosed by geriatricians, neurologists, or psychiatrists, is 6.6%. This closely matches estimates in Western Europe (6.9%) and the United States (6.5%).
The team considered, and adjusted for, numerous covariates: age, sex, socioeconomic status, smoking, depression, obesity, chronic obstructive pulmonary disease, hypertension, atrial fibrillation, heart failure, ischemic heart disease, cerebrovascular disease, diabetes, Parkinson’s disease, traumatic brain injury, migraine, mild cognitive impairment, psychostimulants.
With these adjustments, individuals diagnosed with ADHD were almost three times as likely to be subsequently diagnosed with dementia as those without ADHD. Men with ADHD were two and a half times more likely to be diagnosed with dementia, whereas women with ADHD were over three times more likely, than non-ADHD peers.
More concerning still, persons with ADHD were 5.5 times more likely to be subsequently diagnosed with early onset dementia, as opposed to 2.4 times more likely to be diagnosed with late onset dementia.
On the other hand, the team found no significant difference in rates of dementia between individuals with ADHD who were being treated with stimulant medications and individuals without ADHD. Those with untreated ADHD had three times the rate of dementia. The team nevertheless cautioned, “Due to the underdiagnosis of dementia as well as bidirectional misdiagnosis, this association requires further study before causal inference is plausible.”
Conclusions and Relevance:
This study reinforces existing evidence that adult ADHD is associated with an increased risk of dementia. Notably, the increased risk was not observed in individuals receiving psychostimulant medication, however the mechanism behind this association is not clear.
These findings underscore the importance of reliable ADHD assessment and management in adulthood. They also highlight the need for further study into the link between stimulant medications and the decreased risk of dementia.
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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.
The Background:
Management of ADHD relies on both medications and non-medication approaches. Clinical guidelines often recommend medication as the first-line treatment for adults, while non-medication interventions are often preferred for children. Medicines fall into two main groups: stimulants (for example, methylphenidate and amphetamines), which have strong and well-established evidence and are generally considered first choice, and non-stimulants (such as atomoxetine), which are typically used when stimulants are contraindicated, not tolerated, or ineffective.
How many people with ADHD receive medication is an important indicator of care quality and can be tracked at the national level. Untreated ADHD can affect many areas of life, from physical health, to school and work performance, to relationships emotional well-being. ADHD is associated with poorer quality of life, higher risk of accidents, substance use issues, criminal behavior, educational underachievement, and even increased premature mortality. The condition also places a substantial burden on families and caregivers, so understanding treatment rates matters for individuals and society.
Most epidemiological research has measured how common diagnosed ADHD is, but the share of those diagnosed who actually receive medication can vary a lot. That variation reflects differences in how ADHD is diagnosed, how easy it is to get treatment, what clinical guidelines recommend, and cultural attitudes toward using medication.
The Study:
This paper presents the first comprehensive meta-analysis to estimate how common pharmacological treatment is among children, adolescents, and adults with clinically confirmed ADHD. The analysis included only register-based population studies where diagnoses were confirmed by a qualified healthcare professional. Twelve studies meeting these criteria from Europe (the UK, Sweden, Denmark), Asia (Taiwan, South Korea), and North America (Canada, the United States) were used. Notably, these are all high-income areas, and thus unrepresentative of populations in lower-income countries.
The pooled estimate showed that about 73 percent of diagnosed individuals in prosperous parts of the world with well-developed health care systems were receiving medication, but there was very high variation between studies.
The Results:
The authors conclude there is substantial global variation in ADHD medication use. Overall, a relatively high proportion of people diagnosed with ADHD are treated with medication, which may reflect improved recognition and access to care. The large differences between studies probably reflect differing health systems, diagnostic rules, treatment definitions, study populations, and reporting practices, and they underline the need for more standardized definitions and reporting to make comparisons more meaningful.
There is also a need for information from lower-income regions, but that is complicated by an absence of register-based population studies in countries with more limited health care access.
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The Background:
Because impulsivity is a core feature of ADHD, researchers have suggested it may raise the likelihood that someone will use psychoactive substances (including alcohol) and go on to develop a substance use disorder (SUD). When ADHD and SUD occur together in adolescents, treating one disorder alone usually has little or no positive effect on the other; current guidance therefore recommends treating both conditions at the same time using evidence-based approaches for each.
Given how much ADHD can worsen outcomes for people with primary SUDs, it is important to identify ADHD in people who are being treated for substance problems.
The Study:
A recent systematic meta-review found that, by current official criteria, ADHD affects about 7.2% of children and adolescents and about 2.6% of adults (Chaulagain et al., 2023). When adult ADHD is defined without the requirement that symptoms began by age 11, roughly 6.8% of adults meet criteria. A large body of research links ADHD to higher rates of medical problems, poorer quality of life, greater risk of suicide, more accidental injuries, worse educational outcomes, and increased involvement with the criminal justice system.
The present study is the first meta-analysis to estimate how common clinically diagnosed ADHD is among adults (age 18+) who are in treatment for psychoactive substance use disorders, and to provide those estimates by sex and by the specific substance used.
The authors included only studies of adults treated for a SUD (including alcohol). Eighty-four studies met the criteria, representing more than 34,000 people. Across all studies, the pooled prevalence of clinically diagnosed ADHD was 22%.
To put that in context, 22% is about eight times higher than the 2.6% adult prevalence using the stricter official definition, and about three times higher than the 6.8% rate when the childhood-onset requirement is relaxed. By substance, the prevalence was similar for alcohol (24%) and opioids (22%), with no significant difference between males and females. Prevalence among people treated for cocaine use was somewhat lower overall (18%), driven largely by lower rates among women, for whom the rate was no higher than in the general population. Estimates were higher for people using benzodiazepines and cannabis, but those figures are based on a very small number of users (256 and 249 people, respectively) and are therefore less certain.
The Results:
The authors conclude: “These findings underscore the need for early identification and treatment of ADHD as most substance use disorders develop in adolescence and young adulthood. While in treatment for ADHD, appropriate screening and management of substance use is possible.”
The Background:
Stimulant medications (like methylphenidate and amphetamines) and non-stimulants (like atomoxetine and guanfacine) remain the first-line treatments for ADHD, but their long-term use is often constrained by parental concerns, side effects (reduced appetite, sleep disruption, cardiovascular effects), and the fact that roughly 30% of children respond only partially or not at all. These medications tend to help with attention and behavior, but they do less to address emotional regulation or broader physical health, leaving some parents to seek other safe, complementary treatments.
Nutritional approaches, including omega-3 fatty acids, are one such avenue. Oily fish is the natural source, but clinical trials typically rely on supplements instead, since they allow for precise dosing, avoid the heavy-metal exposure that can come with high fish intake, and sidestep the problem of inconsistent dietary habits. Two omega-3s stand out as particularly relevant: DHA, which supports brain structure and cell-to-cell communication, and EPA, which helps reduce brain inflammation and improve blood flow. Both influence the dopamine and serotonin systems implicated in ADHD.
The Study:
Previous meta-analyses have generally found only modest overall benefits with mixed results. This mixed-results pattern may reflect the fact that children who had low omega-3 levels to begin with stand to benefit more than those whose levels are already adequate. This meta-analysis set out to test that idea directly, asking whether a child's baseline omega-3 status predicts how well they respond to supplementation.
To be included, studies had to be randomized controlled trials (RCTs) involving children diagnosed with ADHD who did not have major coexisting medical conditions. Trials that used broad multinutrient interventions, where the effect of omega-3s specifically couldn't be isolated, were excluded.
The resulting analysis of seven RCTs covering 654 children found small overall improvements in ADHD symptoms with omega-3 supplementation, consistent with earlier meta-analyses. There was little variation across studies, but a clear signal of publication bias, which the authors did not attempt to statistically correct for.
Among four RCTs involving 369 children with low baseline omega-3 levels, supplementation produced a moderate improvement in ADHD symptoms, with consistent results across studies. By contrast, the six RCTs covering 559 children with normal or high baseline omega-3 levels showed no improvement at all, again with consistent results across studies.
The Results:
The authors concluded: this systematic review and meta-analysis offers preliminary evidence that children’s response to long-chain omega-3 supplementation for ADHD may depend on their starting omega-3 nutritional status. Larger effects emerged in the subgroups defined by individual studies as having low baseline levels, while normal, high, or unstratified groups showed little evidence of benefit. In other words, there may be a benefit to children with ADHD taking omega-3 supplements, but only if they are already deficient.
Even still, a sensitivity analysis limited to ADHD symptom-rating scales found only a numerically higher effect in the low-baseline group. This means that these results, though positive, are not considered statistically significant.
The Take-Away:
Given that the evidence rests on just seven trials, that “low baseline” was defined differently across studies (using different biological markers and thresholds), and that several subgroup comparisons were not planned in advance, the authors caution that these findings should be treated as hypothesis-generating rather than conclusive.
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