January 2, 2026

Patient-Centered Outcomes Research Institute (PCORI) to Fund Landmark ADHD Medication Study

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:

  • Is starting with a non-stimulant medication “good enough” compared with starting with a stimulant?
    In other words, when we look at overall improvement in a child’s daily life, not just ADHD symptoms, does a non-stimulant-first approach perform similarly to a stimulant-first approach?
  • Which children do better with which approach?
    Children with ADHD are very different from one another. Some have anxiety, depression, learning problems, or autism spectrum conditions. We want to know whether certain groups of children benefit more from starting with stimulants, and others from starting with non-stimulants.
  • How do the two strategies compare for side effects, treatment satisfaction, and staying on medication?
    We will compare how often children stop or switch medications because of side effects or lack of benefit, and how satisfied children, parents, and clinicians are with care under each strategy.
  • What are the longer-term outcomes over a year?
    We are interested not only in short-term symptom relief, but also in how children are doing months later in school, at home, with friends, and emotionally.

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:

  • Have ADHD and are starting or restarting medication treatment, and
  • Are being treated in everyday pediatric and mental health clinics at large children’s hospitals and health systems across the United States.

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:

  • Each child will be randomly assigned (like flipping a coin) to one of two strategies:


    1. Stimulant-first strategy – the clinician starts treatment with a stimulant medication.
    2. Non-stimulant-first strategy – the clinician starts treatment with a non-stimulant medication.
  • Within the assigned class, the clinician and family still choose the specific medicine and dose, and can adjust treatment as they normally would. This keeps the study as close as possible to real-world practice.
  • The randomization is 1:1, so about half the participants will start with stimulants and half with non-stimulants.

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:

  • Baseline (before or just as medication is started)
  • Early follow-up (about weeks 3 and 6)
  • Later follow-up (about 3 months, 6 months, and 12 months)

At these times:

  • Parents will complete questionnaires about ADHD symptoms, behavior, emotions, and daily functioning at home and in the community.
  • Teachers will complete brief forms about the child’s behavior and performance at school.
  • Children and teens (when old enough) will complete age-appropriate questionnaires about their own mood, behavior, and quality of life.
  • A specially trained clinical rater, using all available information but blinded to treatment strategy, will give a global rating of how much the child has improved overall, not just in ADHD symptoms.

We will also track:

  • Medication changes (stopping, switching, or adding medicines)
  • Reasons for any changes (side effects, lack of benefit, or other reasons)
  • Any serious side effects or safety concerns

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:

  • Compare the overall improvement of children in the stimulant-first group versus the non-stimulant-first group after 12 months.
  • Look at differences in side effects, discontinuation rates, and treatment satisfaction between the two strategies.
  • Examine which child characteristics (such as age, sex, co-occurring conditions, and baseline severity) are linked to better results with one strategy versus the other.
  • Analyze long-term outcomes, including functioning at home, school, and with peers, and emotional well-being.

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:

  • Guidelines are ahead of the evidence.
    Existing guidelines almost always recommend stimulants as the first-line medication, yet careful reviews of the evidence show that direct comparisons of stimulant-first versus non-stimulant-first strategies are limited. We do not have strong data to say that starting with stimulants is clearly superior for all children.
  • Real-world children are more complex than those in past trials.
    Most prior medication trials have excluded children with multiple conditions, serious family stressors, or other complexities that are very common in everyday practice. Our pragmatic, multi-site design will include these children and thus produce findings that are directly relevant to front-line clinicians and families.
  • Families and clinicians are asking for alternatives.
    Parents often express worries about stimulant side effects, long-term use, and stigma. Clinicians would like clearer guidance about when a non-stimulant is a reasonable first choice. At the same time, stimulant shortages and concerns about misuse and diversion have exposed the risks of relying almost entirely on one class of medications.
  • The timing is right to influence practice and policy.
    Our team includes parents, youth advocates, frontline clinicians, and national networks that link major children’s hospitals. These partners have helped shape the study from the beginning and will help interpret and share the results. This means that if starting with non-stimulants is found to be similarly effective and safer or more acceptable for some children, practice patterns and guidelines can change rapidly.

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.

Related posts

ADHD medication and risk of suicide

ADHD Medication and Risk of Suicide

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 ..."

December 13, 2021

Unmedicated Adult ADHD Linked to Dementia in Population Study

Background:

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%). 

Method:

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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February 25, 2025

ADHD Medication and Academic Achievement: What Do We Really Know?

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.

September 17, 2025

What is The Pharmaceutical Supply Chain? Addressing The ADHD Medication Shortage

The persistent shortage of ADHD medications has been more than a simple annoyance for patients at the pharmacy; the inconsistent availability of these medications has had deep impacts on the daily lives of those struggling without them. While public discourse has pointed fingers at over-prescribing or at restrictive DEA quotas, a recent economic evaluation in JAMA Health Forum suggests we’ve been looking in the wrong direction for an answer to what is causing this. 

The reality of the shortage is less about increased demand and more about a fragile, globalized supply chain that snapped at a critical link. 

Debunking the "Quota Myth":

The prevailing narrative suggested that the Drug Enforcement Administration (DEA) was stifling production by refusing to raise quotas. However, the data tells a different story. In 2022, manufacturers collectively met only about 70% of their allotted production quotas. 

So we know that the problem wasn't that this DEA quota ceiling was too low. In fact, most manufacturers couldn't even reach it. Even when accounting for exports and domestic retail, production remained significantly below the legal limit. Even if the DEA had doubled its quotas, these medications still likely wouldn't have magically appeared on pharmacy shelves. 

The most striking finding in the study is the correlation between the shortage and a sharp decline in the import of raw Active Pharmaceutical Ingredients (APIs).  For the past decade, Germany has accounted for over 85% of US amphetamine imports. In 2022, these imports dropped by approximately 36.7%.  When the API doesn't arrive at the factory, production for medium and small manufacturers grinds to a halt. Unlike larger pharmaceutical giants, these smaller players often lack the inventory cushion or flexibility to quickly pivot to a new supplier. 

When the primary supply of amphetamine-based stimulants (like Adderall) faltered, it triggered a secondary crisis. Patients and clinicians, seeking alternatives, shifted toward lisdexamfetamine (Vyvanse) and methylphenidate (Ritalin/Concerta). 

  • Substitution Strain: This sudden migration of millions of patients created a domino effect, eventually leading to shortages in those medications as well. 
  • The Tolerance Gap: As any clinician knows, these stimulants are not perfect substitutes. Switching a stabilized patient to a different class of medication often leads to a trial-and-error period that may be characterized by poor tolerability or reduced efficacy. 

If we view this shortage purely through a regulatory or clinical lens, we miss the underlying cause of the crisis. The pharmaceutical industry has become a victim of its reliance on "just-in-time manufacturing” and highly concentrated sourcing.  Because over 30% of APIs for the US market are produced in just one or two facilities globally, the system isn't just inefficient; it’s brittle. We are, in a sense, trapped in a system that prioritizes cost-reduction over the resilience required for public health. 

The researchers suggest several policy shifts to prevent a repeat of this supply chain failure: 

  1. Increased Transparency: The FDA should require manufacturers to disclose their specific API suppliers. 
  1. Risk Assessment: Identifying "vulnerable" drugs that rely on fewer than three production facilities worldwide. 
  1. Regulatory Flexibility: Streamlining the process for manufacturers to switch API suppliers during a documented national shortage. 

The ADHD medication shortage wasn't a failure of clinical oversight or a sudden surge in "TikTok-driven diagnoses”, as many have suggested. It was a failure of logistics. It reminds us that the path from a lab in Germany to a patient's hand in the US is far more precarious than we realized. 

July 6, 2026

Brain Stimulation Therapy Shows No Benefit for ADHD in New Meta-analysis

ADHD is a neurodevelopmental condition rooted in delayed or atypical maturation of the prefrontal cortex  (the brain region that governs self-regulation). This maturational lag underlies the hallmark difficulties with attention, hyperactivity, and impulsivity, and also impairs what researchers call executive function: the cognitive toolkit we rely on for working memory, impulse control, mental flexibility, emotional regulation, and the ability to tolerate delays in reward. 

The Background:

Standard treatments work through two main routes. Stimulant and non-stimulant medications are considered very safe and effective treatments, but are not without risk of side effects and are not appropriate for every ADHD patient. Behavioral and psychosocial interventions can improve self-regulation and social functioning, but they require sustained effort and produce variable results. These limitations have kept the search for better alternatives active. 

One candidate that has drawn growing attention is transcranial direct current stimulation (tDCS). The technique is appealingly simple: a weak electrical current is applied to the scalp through small electrodes, modulating the excitability of neurons in the underlying cortex without requiring surgery, anesthesia, or significant discomfort. Its safety profile and ease of use have made it attractive to researchers. 

The Study: 

A newly published meta-analysis set out to give the technique its most rigorous test yet, pooling results from randomized controlled trials, including crossover designs, that compared active tDCS against sham stimulation in people with ADHD across all age groups. 

The Results: 

The findings were consistently null. Across seven trials enrolling 303 participants, tDCS produced no significant reduction in overall ADHD symptom severity compared with sham. Breaking symptoms into their components made no difference: neither hyperactivity/impulsivity nor inattention improved. Turning to executive function, 18 studies with 872 participants found no meaningful gain in inhibitory control, and 12 studies with 506 participants found the same for working memory. Smaller bodies of evidence, including three studies on cognitive flexibility (122 participants) and two on hot executive function, the motivational and emotional dimension of self-regulation (86 participants),  similarly came up empty. Variation in outcomes across studies was small to moderate, and there was no evidence of publication bias skewing the picture. 

The authors’ conclusion was succinct: tDCS was well tolerated but “did not demonstrate significant overall efficacy for core ADHD symptoms or executive functions.” 

July 2, 2026

Children and Adolescents with ADHD Face Significantly Higher Risk of Disordered Eating, Large U.S. Study Finds

Disordered eating (a broad category of persistent, harmful patterns in eating or weight control) affects between 5% and 22% of children and adolescents worldwide, with similar rates seen in the United States. The consequences are far-reaching: these conditions are linked to bone fractures, anemia, malnutrition, dental erosion, obesity, diabetes, hypertension, and elevated cholesterol and triglycerides. They also carry one of the highest mortality rates of any psychiatric illness. 

Eating disorders rarely occur in isolation. They frequently arise alongside other psychiatric and neurological conditions. Yet, until now, no large-scale study had examined these co-occurrences in a nationally representative U.S. sample. A new study addresses that gap, focusing on children and adolescents aged 6–17 and the conditions most commonly associated with disordered eating, including ADHD. 

The Study: 

Researchers drew on data from the 2022–2023 National Survey of Children's Health (NSCH), a nationally representative, cross-sectional survey covering all 50 states and Washington, D.C. Households were selected using stratified, address-based sampling, and parents or guardians completed surveys about one randomly selected child per household. The final sample included 68,000 children and adolescents. 

Results: 

After accounting for factors including sex, age, race and ethnicity, household income, educational attainment, insurance status, and household language, children and adolescents with ADHD were 2.6 times more likely to have some form of disordered eating compared to their typically developing peers. 

The elevated risk appeared across a range of specific behaviors: 

  • 60% more likely to over-exercise 
  • Twice as likely to experience a fear of vomiting or choking 
  • 2.4 times more likely to be extremely selective eaters, to skip meals, or to fast 
  • 2.7 times more likely to purge food or vomit 
  • 3 times more likely to show little interest in food 
  • 3.2 times more likely to binge eat 

A greater tendency toward using diet pills, laxatives, or diuretics was also observed in the ADHD group, though this finding did not reach statistical significance. 

The Take-Away: 

These findings underscore a need to improve both prevention and treatment strategies for disordered eating, particularly in children and adolescents who have ADHD. Clinicians working with this population are advised to screen for a wide spectrum of disordered eating behaviors.