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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.

Recent research from the Centers for Disease Control and Prevention (CDC) highlights distinct health and social-emotional challenges faced by teens diagnosed with Attention-Deficit/Hyperactivity Disorder (ADHD). This study, published in the Journal of Developmental and Behavioral Pediatrics, offers critical insights directly from the teens themselves, providing a unique view often missed when relying solely on parent or clinical reports.
Researchers analyzed nationally representative data from July 2021 through December 2022, comparing self-reported experiences of teens aged 12 to 17 with and without ADHD. Approximately 10% of teenagers had an ADHD diagnosis, and the findings reveal specific areas where teens with ADHD face notable difficulties.
Teenagers with ADHD reported significantly higher rates of bullying victimization and struggles in making friends compared to their peers. Surprisingly, they were less likely to report a lack of peer support, suggesting complexities in how they perceive friendships and social networks. The study underscores the importance of directly engaging teens in assessing their social relationships, rather than solely relying on parental perspectives.
Sleep difficulties emerged as another critical issue for teens with ADHD. About 80% reported problems like difficulty waking up and irregular wake times, markedly higher than their non-ADHD counterparts. Such disruptions can exacerbate attention difficulties and emotional regulation issues, further complicating daily life for these teens.
Excessive screen time also stood out, with nearly two-thirds of teens with ADHD spending over four hours daily on screens, excluding schoolwork. This high screen usage is concerning, given its potential negative impact on physical and mental health, including sleep quality and social interactions.
Notably, the study found no significant differences in physical activity levels or concerns about weight between teens with and without ADHD. This finding contrasts with previous studies that have highlighted lower physical activity among children with ADHD, suggesting the need for continued research on how physical activity is measured and encouraged in this population.
The study’s authors emphasize the importance of health promotion interventions tailored specifically for teens with ADHD. By directly engaging teens and considering their unique perspectives, interventions can better address social-emotional well-being and healthy lifestyle behaviors, ultimately improving long-term outcomes for this vulnerable group.
Overall, this research provides compelling evidence for healthcare providers, educators, and families to focus on supporting teens with ADHD in areas of social skills, sleep hygiene, and healthy screen time habits. Such targeted support can significantly enhance the quality of life and health outcomes for adolescents navigating the challenges of ADHD.

Methylphenidate is known as the gold-standard treatment for ADHD, increasing dopamine concentrations and helping to focus. However, these psychostimulants may be less well-tolerated in adults. Adverse effects include decreased appetite, nausea, racing heartbeat, restlessness, nervousness, and insomnia.
Neurofeedback is a non-pharmaceutical treatment that combines cognitive behavioral therapy techniques like conditioning and positive reinforcement with electroencephalography (EEG) feedback. Electrodes are placed on specific brain areas, guiding patients to regulate their brainwave activity.
Repetitive transcranial magnetic stimulation (rTMS) uses electromagnetism to induce an electric field by passing a magnetic field through the scalp. Transcranial direct current stimulation (tDCS), on the other hand, directly applies an electric current through the scalp. Both repetitive transcranial magnetic stimulation (rTMS) and tDCS primarily target the outermost layers of neurons, as they are non-invasive methods. Nevertheless, both techniques are believed to affect deeper layers through interconnected neuronal networks.
A French research team conducted a systematic search of the peer-reviewed medical literature to perform a meta-analysis to explore the efficacy of these experimental treatment techniques.
Eight studies – four using rTMS and another four using tDCS – met the inclusion criteria. Studies had to be randomized controlled trials (RCTs), and had to involve multiple sessions of treatment. Participants had to be adults previously diagnosed with ADHD.
Outcomes were measured through self-rated scales, neuropsychological tests, and electrophysiological pre-post evaluations.
Separate meta-analyses of the four tDCS RCTs combining 154 participants and of the four rTMS RCTs encompassing 149 participants likewise reported no significant improvements. In all cases variation in outcomes between studies was moderate, and there were no signs of publication bias.
Meta-analysis of all eight studies with a combined total of 421 participants reported no significant improvements over controls. Narrowing down to studies that used sham controls likewise produced no significant improvements. So, despite the title of this study, these neuromechanistic treatments do not appear to be the future of treatment for adult ADHD.
According to the World Health Organization, suicide is the second leading cause of death among individuals aged 15 to 29 years.
A European study team recently released findings of the first meta-analysis to explore the association between clinically diagnosed ADHD in children and adolescents and subsequent suicidality.
The criteria for study inclusion were:
All selected studies scored at least eight out of 11 points after quality assessment. The most frequent defect was that it was unclear whether suicidal behavior had occurred before study initiation.
Meta-analysis of all nine included studies, encompassing more than 4.4 million participants, reported more than threefold greater odds of overall suicidal behavior among children and adolescents previously diagnosed with ADHD, as opposed to children and adolescents not previously diagnosed with ADHD. Study outcomes varied significantly (high heterogeneity) but showed no publication bias.
Breaking this down into subcategories of risk:
The team concluded, “the current systematic review and meta-analysis has confirmed previous findings that there is an elevated risk for suicidal behavior in ADHD patients.” They also note, however, that “this relationship is heterogeneous and complex, with significant differences across ADHD subtypes, age groups, sexes, comorbidities, and social issues, all of which play important roles in the development of suicidal behavior.”

Centanafadine, which is currently under investigation as a treatment for ADHD, will be the first triple reuptake inhibitor for the disorder if it is approved by the FDA. It improves norepinephrine, dopamine and serotonin levels. This new medication is not a stimulant, but due to the dopamine component, it has a stimulant-like effect in patients. In adults, two phase 3 trials and a year-long extension have shown sustained benefits and a tolerable safety profile, laying the groundwork for pediatric research.
Based on this study, improvement was already noticeable after the first week and held steady through week 6. The lower dose (164.4 mg) didn’t separate from placebo, reminding us that getting the dose right will be critical. The effect size was smaller than what is seen for stimulants but 50% of patients had excellent outcomes as indicated by reductions in the ADHD-RS of 50% or more.
Side effect patterns look familiar to anyone who prescribes ADHD medications; loss of appetite, nausea and headaches topped the list. About half of teens on the higher dose reported at least one treatment-emergent adverse event, compared with a quarter of those on placebo. Severe reactions were rare but did include isolated liver enzyme spikes, rash, and a few reports of aggression or somnolence. For everyday practice, that translates to routine growth checks, a look at baseline liver function, and clear guidance to families about reporting rashes or mood changes promptly.
The researchers noted that the study had certain limitations, including limited generalizability to adolescents beyond North America, the exclusion of teacher ratings on the ADHD-RS-5 scale and the study’s short duration. They added that future studies should explore long-term treatment outcomes and efficacy compared with other ADHD treatments, as well as its effect on treating ADHD with comorbid conditions.
First, speed. Centanafadine separated from placebo within a week. In this regard, it might be closer to stimulants than to the multi-week ramp-up we expect from current non-stimulants. Second, it offers another option when stimulants are contraindicated or poorly tolerated, or when they raise diversion concerns. Its mechanism also makes it intriguing for patients who need both norepinephrine and dopamine coverage but prefer to avoid schedule II drugs. Because it also improves serotonergic transmission, it may be useful for some of ADHD’s comorbidities (see our new article for evidence about serotonin’s role in these disorders).
Keep in mind that centanafadine for ADHD is still investigational, so participation in clinical trials remains the only access route.

A recent in-depth clinical review published by the American Academy of Neurology examines how ADHD manifests in adulthood and how neurologists can differentiate it from other causes of attention problems.
Recognition of ADHD in adults by clinicians is often delayed or misdiagnosed due to overlapping symptoms with anxiety, depression, sleep disorders, and life stressors. Conversely, as ADHD in adults becomes more widely acknowledged, largely due to increased public awareness and social media trends, clinicians need to take extra care not to incorrectly diagnose patients with ADHD. This publication aims to shine a light on both sides of this issue and highlight the importance of clinicians being trained in proper ADHD screening.
The article highlights how many adults come to neurology clinics convinced they have ADHD after online quizzes or watching others get diagnosed. True ADHD must be differentiated from issues with shared signs and symptoms such as poor sleep, anxiety, depression, or even OCD or Bipolar Disorder. This is a high-level clinical skill called differential diagnosis.
The author of the article, Dr. Mierau, provides detailed clinical strategies such as asking open-ended questions, exploring how symptoms show up at home and at work, and watching for patterns like chronic lateness or emotional overeating. (This paper points out that, while not included in the DSM-VI, food cravings and binge behaviors are commonly found in patients with ADHD.)
This review correctly emphasizes that neuropsychological testing is not necessary for diagnosis. Instead, a thorough clinical interview, including a detailed family history and behavioral observation, can be more telling.
The review article closes with a call to action: the biggest obstacle isn’t diagnosing or treating ADHD, it’s access. Adults struggle with pharmacy shortages, no-refill laws, and insurance hurdles, despite research showing treatment reduces mortality and improves life quality. Dr. Mierau argues for more trained providers, better public education, and policy changes to reduce stigma and expand access.

Good science isn’t static: We’re updating past blogs to reflect new findings and higher‑quality evidence.
The Background on ADHD and Vitamin D:
In a blog published in the early days of The ADHD Evidence Project, we discussed an Iranian study examining the association between Vitamin D levels and ADHD in children. The meta-analysis combined 13 studies for a total of 10,344 participants. The researchers found that youth with ADHD had "modest but significant" lower serum concentrations of 25-hydroxyvitamin D compared to those without ADHD.
They also identified four prospective studies that compared maternal vitamin D levels with the subsequent development of ADHD symptoms in their children. Two of these used maternal serum levels, and two used umbilical cord serum levels. Together, these studies found that low maternal vitamin D levels were associated with a 40% higher risk of ADHD in their children.
Ultimately, the researchers noted that this result "should be considered with caution" because it was heavily dependent on one of the prospective studies included in the analysis. We concluded our blog by pointing out that further research, including more longitudinal studies, is needed before clinicians should start recommending vitamin D supplementation to ADHD patients.
Further Research:
Since publishing that initial blog, several more studies have been published about this association.
The World Federation of Societies of Biological Psychiatry (WFSBP) and the Canadian Network for Mood and Anxiety Disorders (CANMAT) convened an international task force involving 31 leading academics and clinicians from 15 countries between 2019 and 2021. Their goal was to provide a definitive, evidence-based report to assist clinicians in making decisions around the recommendation of nutraceuticals and phytoceuticals for major psychiatric disorders.
For ADHD, the guidelines found only weak support for micronutrients and vitamin D in treatment. Overall, the task force concluded that nutraceuticals and phytoceuticals currently offer very limited evidence‑based benefit for ADHD management.
Another study published in 2023 systematically assessed the results of previously published studies to examine the associations between maternal vitamin D levels, measured as circulating 25(OH)D levels in pregnancy or at birth, and later offspring psychiatric outcomes. This study found a clear association between maternal vitamin D deficiency and subsequent offspring ADHD. They concluded, “Future studies with larger sample sizes, longer follow-up periods, and prenatal vitamin D assessed at multiple time points are needed.” To that, I will add that studies of this issue should use genetically informed designs to avoid confounding.
Conclusion:
Taking into account the updated research on the topic, there does seem to be an association between low prenatal vitamin D levels and the risk of subsequent offspring ADHD, but it is too soon to say it is a causal relationship due to the possibility of confounding. There is no high-quality evidence, however, that supplementing with vitamin D will significantly reduce symptoms in current ADHD patients.

New research has uncovered important links between certain blood metabolites and ADHD by using a genetic method called Mendelian randomization. This approach leverages natural genetic differences to help identify which metabolites might actually cause changes in ADHD risk, offering stronger clues than traditional observational studies.
Key Metabolic Pathways Involved:
The study found 42 plasma metabolites with a causal relationship to ADHD. Most fall into two major groups:
Since many metabolites come from dietary sources like proteins and fats this supports the idea that diet could influence metabolic pathways involved in ADHD. However, because the study focused on genetic influences on metabolite levels, it doesn’t directly prove that dietary changes will have the same effects.
Notable Metabolites:
Five metabolites showed bidirectional links with ADHD, meaning genetic risk for ADHD also affects their levels which suggests a complex interaction between brain function and metabolism.
Twelve ADHD-related metabolites are targets of existing drugs or supplements, including:
While these findings highlight biological pathways, they don’t prove that changing diet will directly alter ADHD symptoms. Metabolite levels are shaped by genetics plus environment, lifestyle, and health factors, which require further study.
Conclusion:
This research provides stronger evidence of metabolic pathways involved in ADHD and points to new possibilities for diagnosis and treatment. Future work could explore how diet or drugs might safely adjust these metabolites to help manage ADHD.
While this study strengthens the link between amino acid and fatty acid metabolism and ADHD risk, suggesting that diet could play a role, ultimately more research is still needed before experts could use this research to give specific nutritional advice.

Background Info:
Executive functions include inhibitory control, working memory, and cognitive flexibility. Inhibitory control is the ability to suppress distractions and focus on goals, which is the main deficit in ADHD.
Children and adolescents with ADHD often have off-task, unrelated thoughts and are easily distracted, limiting their sustained attention. This makes it difficult for them to focus on tasks and leads to impulsive behaviors that affect their daily life, academics, and social interactions. Improving inhibitory control in ADHD children and adolescents is essential.
Stimulant medications are commonly used to treat ADHD. However, side effects like insomnia, loss of appetite, and headaches may make parents hesitant to use these medications for their children.
Non-pharmacological treatments like cognitive training, behavior therapy, and physical exercise have gained attention for their lack of side effects. Research shows that some non-pharmacological methods can improve cognitive outcomes significantly, underscoring their potential in treating ADHD.
Study:
A Chinese research team identified four key gaps in current research on non-pharmacological treatments for inhibitory control in children with ADHD:
The team therefore performed a network meta-analysis of long-term randomized controlled trials (RCTs) to assess and rank the effectiveness of various non-pharmacological treatments on inhibitory control in children and adolescents with ADHD.
The team included only RCTs relying on professional diagnoses of ADHD, excluding those based only on parent and teacher rating scales.
The included studies measured inhibitory control using objective neurocognitive tasks, such as the Stroop test and the Go/No-Go test, to reduce potential subjective bias. Studies relying on parent- or teacher-reported questionnaires were excluded.
Controls either received no intervention or placebo, such as watching running videos and attending history classes.
Meta-analysis of 16 studies combining 546 participants found large short-term effect size improvements in inhibitory control from physical exercise. But the two studies with a total of 110 participants that performed a follow-up test reported only a small-to-medium effect size improvement.
For cognitive training, a meta-analysis of fifteen studies totaling 674 participants reported a medium effect size of short-term improvement in inhibitory control. The ten studies with 563 participants that performed a follow-up test found only a small effect size improvement since treatment initiation.
For behavioral therapy, meta-analysis of six studies encompassing 244 individuals likewise found a medium effect size short-term improvement in inhibitory control. In this case, however two studies combining 91 participants that performed a follow-up test reported that the medium effect size improvement was maintained.
For neurofeedback, meta-analysis of seven studies encompassing 186 individuals found a small-to-medium effect size short-term improvement in inhibitory control. The only study that performed a follow-up test reported a small effect size improvement since treatment initiation.
The two studies with a combined 44 individuals exploring board games found no significant improvement in inhibitory control. Likewise, the two studies combining 32 participants that explored meditation found no significant improvement in inhibitory control.
There was no indication of publication bias.
Conclusion:
The team concluded, “Existing evidence shows that physical exercise, behavior therapy, cognitive training, and neurofeedback can effectively improve the inhibitory control of children and adolescents with ADHD. However, meditation, EMG feedback, and board games did not significantly affect inhibitory control. Physical exercise has the best effect among all non-pharmacological treatments, but its impact will be weakened after intervention. Behavior therapy and cognitive training had a slightly lower effect, but they have a better maintenance effect.”
Ultimately, the study results suggest that non-drug treatments can help children and teens with ADHD improve their ability to control their actions and stay focused. Some methods, like physical exercise, work well at first but may fade once the activity stops. Other methods, like behavioral therapy and cognitive training, may take a little longer to show results but can last longer and make a bigger difference over time. Ultimately, and most importantly, because this work did not study the symptoms of ADHD or its real-world impairments, it provides no reason to change current treatment practices for ADHD.

Serotonin is a key chemical in the body that helps regulate mood, behavior, and also many physical functions such as sleep and digestion. It has also been linked to how ADHD (attention-deficit/hyperactivity disorder) develops in the brain. This study looks at how serotonin may be involved in both the mental health and physical health conditions that often occur alongside ADHD.
It is well-established that ADHD is more than just trouble focusing or staying still. For many, it brings along a host of other physical and mental health challenges. It is very common for those with ADHD to also have other diagnosed disorders. For example, those with ADHD are often also diagnosed with depression, anxiety, or sleep disorders. When these issues overlap, they are called comorbidities.
A new comprehensive review, led by Dr. Stephen V. Faraone and colleagues, delves into how serotonin (5-HT), a major brain chemical, may be at the heart of many of these common comorbidities.
Serotonin is a neurotransmitter most often linked to mood, but its role in regulating the body has much broader implications. It regulates sleep, digestion, metabolism, hormonal balance, and even immune responses. Although ADHD has long been associated with dopamine and norepinephrine dysregulation, this review suggests that serotonin also plays a central role, especially when it comes to comorbid conditions.
This research suggests that serotonin dysregulation could explain the diverse and sometimes puzzling range of symptoms seen in ADHD patients. It supports a more integrative model of ADHD—one that goes beyond the brain’s attention, reward and executive control circuits and considers broader physiological and psychological health.
future research into the role of serotonin could help develop more tailored interventions, especially for patients who don't respond well to stimulant medications. Future studies may focus on serotonin’s role in early ADHD development and how it interacts with environmental and genetic factors.
This study is a strong reminder that ADHD is a complex, multifaceted condition. Differential diagnosis is crucial to properly diagnosing and treating ADHD. Clinicians' understanding of the underlying link between ADHD and its common comorbidities may help future ADHD patients receive the individualized care they need. By shedding light on serotonin’s wide-reaching influence, this study may provide a valuable roadmap for improving how we diagnose and treat those with complex comorbidities in the future.

Our recent study, published in the Journal of Clinical Medicine, aims to shed light on an under-recognized challenge faced by many adults with Type 1 diabetes (T1D): attention-deficit/hyperactivity disorder (ADHD) symptoms.
We surveyed over 2,000 adults with T1D using the Adult Self-Report Scale (ASRS) for ADHD and analyzed their medical records. Of those who responded, nearly one-third met the criteria for ADHD symptoms—far higher than the general population average. Notably, only about 15% had a formal diagnosis or were receiving treatment.
The findings are striking: individuals with higher ADHD symptom scores had significantly worse blood sugar control, as indicated by higher HbA1c levels. Those flagged as "ASRS positive" were more than twice as likely to have poor glycemic control (HbA1c ≥ 8.0%). They also reported higher levels of depressive symptoms.
As expected, ADHD symptoms decreased with age but remained more common than in the general public. No strong links were found between ADHD symptoms and other cardiometabolic issues.
This study highlights a previously overlooked yet highly significant factor in diabetes management. ADHD-related difficulties—such as forgetfulness, inattention, or impulsivity—can make managing a complex condition like T1D more difficult. The researchers call for more screening and awareness of ADHD in adults with diabetes, which could lead to better mental health and improved blood sugar outcomes.
Takeaway: If you or a loved one with T1D struggles with focus, organization, or consistent self-care, it may be worth exploring whether ADHD could be part of the picture. Early identification and support are crucial to managing this common comorbidity.