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

New Expert Guidance on "Deprescribing" Stimulants for Adults with ADHD

The Background: 

Over the past two decades, diagnostic rates for adult ADHD have roughly doubled, and stimulant prescriptions in the United States skyrocketed by more than 50% between 2012 and 2023, particularly among girls and women. While these medications help many individuals manage their symptoms, a landmark 2026 article published in European Neuropsychopharmacology tackles an important question that is rarely discussed: When should doctors and patients consider stopping them?  

The Discussion: 

To answer this, the American Society of Clinical Psychopharmacology (ASCP) gathered a task force of 45 international experts spanning 12 countries. Through a rigorous evaluation process, they reached an overwhelming agreement on a framework for "deprescribing", the planned, supervised reduction or cessation of a medication. Here are the core insights from these ground-breaking guidelines and what they mean for adults navigating long-term ADHD treatment.  

When the Treatment Isn’t Yielding Benefits 

One of the most straightforward reasons to consider stopping a stimulant is if it simply isn’t doing its job. The task force agreed that if a patient does not experience an optimal response, measured by actual symptom reduction, improved daily functioning, and a better quality of life, even after trying a high, optimized dose, it may be time to step back and look at alternative options.  

Sometimes, the issue goes back to the initial evaluation. The criteria for diagnosing ADHD have expanded over the years, and brief psychiatric evaluations can occasionally lead to diagnostic inaccuracies. If a thorough reevaluation reveals that the original ADHD diagnosis was incorrect, the expert consensus is clear: stimulant deprescribing is appropriate unless another stimulant-responsive condition is evident. Furthermore, if a patient develops a persistent tolerance to the drug that cannot be resolved by safe dose adjustments, a temporary taper or drug holiday may be recommended.  

When the Risks to Health Outweigh the Rewards 

Our bodies and health needs naturally shift over time, meaning a medication that worked safely years ago might pose a threat to your health today. The experts concluded that deprescribing should be heavily considered if stimulants exacerbate a concurrent medical or psychiatric illness. For example, although rare, stimulants can unintentionally trigger mania or psychosis in adults with unstable or unrecognized comorbid bipolar disorder.  

Physical health developments are equally critical. If an adult develops a newly arising or unstable cardiovascular condition, such as a cardiac arrhythmia, ischemia, or cardiomyopathy, the risk-benefit balance changes dramatically. Additionally, if severe side effects occur that cannot be managed by reducing the dosage, or if dangerous new drug-drug interactions emerge, stopping the medication under medical supervision protects the patient's long-term well-being.  

Addressing Misuse and the Complex Role of Cannabis 

Because stimulant medications target brain reward and wakefulness circuitry, they can foster a propensity for misuse. Studies indicate that more than 1 in 5 adults prescribed stimulants have misused them, and 1 in 6 have diverted their medication to others. The task force emphasizes that deprescribing is warranted if a patient persistently takes doses higher than prescribed against medical advice, uses the medication purely for unauthorized performance enhancement, or has an untreated, coexisting substance use disorder.  

And what about cannabis? This topic sparked the most debate among the experts, falling just short of an official consensus with 71% agreement that regular cannabis use alone shouldn't automatically trigger a stimulant stoppage. Recognizing the complexity, such as how chronic cannabis use can overlap with ADHD executive function deficits, the task force proposed a structured monitoring approach instead of an immediate cutoff. Clinicians are encouraged to track the patient every 1 to 3 months using standardized symptom tools and random urine drug screens to verify whether cannabis use is actively neutralizing the stimulant's therapeutic benefits.  

The Path Forward: Safe Tapering and Lifestyle Support 

If you and your doctor decide that stopping a stimulant is the right path, it shouldn’t happen overnight. The task force strongly recommends that medications be gradually tapered off at a rate tailored to the individual to minimize potential disruptions and distinguish between transient withdrawal and a true return of ADHD symptoms.  

Crucially, stopping a medication doesn't mean stopping treatment. The experts highlight that the success of any deprescribing plan is significantly enhanced when patients focus on optimizing modifiable lifestyle factors. Prioritizing sleep hygiene, staying physically active, and implementing structured behavioral strategies can support executive functioning and help sustain your cognitive gains even as the medication is reduced or eliminated.  

The Takeaway: 

The decision to continue or stop an ADHD medication is a deeply personal one that requires balancing real-world efficacy, safety, and individual health changes. These new consensus recommendations provide an essential roadmap to help adults navigate their long-term mental health journeys safely and effectively.  

Are you or a loved one currently evaluating your long-term relationship with ADHD medication? Consider scheduling a check-in with your healthcare provider to discuss whether your current treatment plan still perfectly matches your health needs today. 

ADHD and Health: How Sex Differences Impact Physical Health into Adulthood

Girls are diagnosed with ADHD at less than half the rate of boys, but this gap closes significantly by adulthood. ADHD also looks different in females than in males, with distinct patterns in symptoms, development, functional impairment, economic impact, and long-term outcomes. Despite this, sex differences in how ADHD relates to physical health have been poorly studied. 

Prior research has established that both children and adults with ADHD face elevated risk for a range of physical health conditions. But that work has been hampered by small samples, retrospective designs, and limited population coverage. 

The Study

Denmark's single-payer national health system makes it possible to conduct truly population-wide research. This study drew on Danish national registers to follow more than 825,000 individuals, born between 1984 and 1995, from birth through adolescence and into young adulthood, tracking them across 13 categories of physical disease. Only individuals free of a relevant physical diagnosis at birth were included, and ADHD diagnosis was treated as something that could be acquired over time rather than a fixed characteristic. 

The Results: 

Across both sexes, people diagnosed with ADHD consistently showed higher disease risk than the general population, with cancer being the one notable exception. The absence of a meaningful cancer signal is expected, given that cancer predominantly affects older age groups than those captured in this study. 

For most other disease categories (including infectious, endocrine, metabolic, respiratory, digestive, musculoskeletal, and genitourinary diseases), elevated risk emerged in early adolescence. For the remaining categories, elevated risk was present at all ages studied. 

The magnitude of these risks was often substantial: 

  • Infectious diseases: Males aged 14–23 with ADHD faced about 20% greater risk than peers without ADHD; females in the same age group faced roughly 80% greater risk. These differences converged to around 45% above baseline beyond that age. 
  • Eye diseases: Before age 11, males with ADHD had more than twice the risk of their non-ADHD peers; females had more than five times the risk. By age 22, both sexes converged at roughly 35% above baseline. 
  • Ear diseases: Risk was more than five times higher in children with ADHD under age 7. 
  • Nervous system diseases: Risk more than doubled across all ages studied. 
  • Endocrine, nutritional, and metabolic diseases: Risk more than doubled between ages 7 and 23. 
  • Skin conditions: Risk more than doubled through age 11. 

By early adulthood, individuals with ADHD showed at least 20% greater risk across every disease category except cancer, regardless of sex. 

Sex Differences Shift With Age 

One of the study's more nuanced findings concerns how sex interacts with ADHD diagnosis over time. In the general population, females tend to have higher physical disease risk from the teenage years onward, while males show higher risk in early childhood. ADHD diagnosis disrupted these patterns unevenly, amplifying risk in some groups and age windows more than others. 

Perhaps most notably, the transition into young adulthood appeared to reduce the ADHD-associated gap between the sexes for endocrine, nutritional, and metabolic diseases (from a ninefold female-to-male disparity down to roughly 4.5-fold). The authors suggest this may reflect ADHD's influence on sex hormone activity during this developmental period. 

Takeaway 

This large, population-representative study confirms that an ADHD diagnosis is associated with meaningfully elevated risk across nearly all categories of physical disease, and that this relationship is neither uniform across sexes nor static across the lifespan. The findings underscore the need for sex-sensitive, developmentally informed approaches to the physical healthcare of people with ADHD. 

Antidepressants in Pregnancy and ADHD Risk: What a Major New Analysis Found

Antidepressants are the primary drug treatment for depressive disorders, which affect 15–20% of pregnant women. They are among the most widely prescribed medications worldwide, and their use has increased in recent decades. Understanding their reproductive safety is critical to support informed, evidence-based prescribing during pregnancy. 

A new meta-analysis sheds important light on one of the most debated concerns: whether children born to mothers who took antidepressants during pregnancy face a higher risk of ADHD. 

The Study: 

Pooling 14 studies covering more than 14 million participants, the analysis found that prenatal antidepressant exposure was associated with a 35% higher rate of ADHD in offspring compared to no exposure. A separate look at SSRIs (the most widely prescribed class of antidepressants, including Prozac and Zoloft) across 11 studies and over four million pregnancies found an even higher apparent risk (44%)  after correcting for publication bias. On the surface, these are striking numbers. 

Both associations came with an important caveat: enormous variation between individual studies, a statistical red flag suggesting the results may not reflect a true underlying effect. More tellingly, the apparent risk evaporated entirely when researchers applied a more rigorous method — comparing siblings within the same family, where one child was exposed to antidepressants in the womb, and another was not. 

This sibling-comparison design is particularly powerful because it automatically controls for factors that run in families: shared genes, household environment, parenting, and socioeconomic conditions. When those influences are held constant, the link between antidepressant exposure and ADHD disappears. The same pattern held for SSRIs specifically. 

Two other antidepressant classes, SNRIs (serotonin norepinephrine reuptake inhibitors) and tricyclics, showed no significant association in any analysis. 

“Confounding by Indication”: 

The probable driver of the initial association is what researchers call confounding by indication. The very condition being treated (depression) is itself a risk factor for ADHD in offspring, independently of any medication. Mothers with more severe depression are also more likely to be prescribed antidepressants, meaning the drug and the underlying illness are difficult to disentangle in standard analyses. Sibling studies cut through this problem cleanly. 

The Take-Away: 

The authors concluded that the association between antidepressants and ADHD risk was non-significant across all analyses designed to account for these confounding factors. This doesn’t mean antidepressants are without any reproductive considerations, but it does suggest that ADHD risk, at least, is driven by heritable and family-level factors rather than medication exposure itself. 

For clinicians and patients weighing the risks of treating or not treating depression during pregnancy, this distinction matters considerably.