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August 5, 2025
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.
Adler, Lenard A. MD1; Adams, Julie MD2; Madera-McDonough, Jessica MD2; Kohegyi, Eva MD2; Hobart, Mary PhD2; Chang, Denise PhD2; Angelicola, Mark MS2; McQuade, Robert PhD2; Liebowitz, Michael MD3. Efficacy, Safety, and Tolerability of Centanafadine Sustained-Release Tablets in Adults With Attention-Deficit/Hyperactivity Disorder: Results of 2 Phase 3, Randomized, Double-blind, Multicenter, Placebo-Controlled Trials. Journal of Clinical Psychopharmacology 42(5):p 429-439, 9/10 2022. | DOI: 10.1097/JCP.0000000000001575
Raising children is not easy. I should know.
As a clinical psychologist, I've helped parents learn the skills they need to be better parents. And my experience raising three children confirmed my clinical experience.
Parenting is a tough job under the best of circumstances, but it is even harder if the parent has ADHD.
For example, an effective parent establishes rules and enforces them systematically. This requires attention to detail, self-control, and good organizational skills. Given these requirements, it is easy to see how ADHD symptoms interfere with parenting. These observations have led some of my colleagues to test the theory that treating ADHD adults with medication would improve their parenting skills. I know about two studies that tested this idea.
In 2008, Dr. Chronis-Toscano and colleagues published a study using a sustained-release form of methylphenidate for mothers with ADHD. As expected, the medication decreased their symptoms of inattention and hyperactivity/impulsivity. The medication also reduced the mother's use of inconsistent discipline and corporal punishment and improved their monitoring and supervision of their children.
In a 2014 study, Waxmonsky and colleagues observed ADHD adults and their children in a laboratory setting once when the adults were off medication and once when they were on medication. They used the same sustained-release form of amphetamine for all the patients. As expected, the medications reduced ADHD symptoms in the parents. This laboratory study is especially informative because the researchers made objective ratings of parent-child interactions, rather than relying on the parents' reports of those interactions. Twenty parents completed the study. The medication led to less negative talk and commands and more praise by parents. It also reduced negative and inappropriate behaviors in their children.
Both studies suggest that treating ADHD adults with medication will improve their parenting skills. That is good news. But they also found that not all parenting behaviors improved. That makes sense. Parenting is a skill that must be learned. Because ADHD interferes with learning, parents with the disorder need time to learn these skills. Medication can eliminate some of the worst behaviors, but doctors should also provide adjunct behavioral or cognitive-behavioral therapies that could help ADHD parents learn parenting skills and achieve their full potential as parents.
Few studies have examined the safety and tolerability of ADHD medications (stimulants and atomoxetine) extending beyond six months, and none beyond a few years. A pair of Swedish neuroscientists at Uppsala University Hospital set out to explore longer-term outcomes. They conducted a six-year prospective study of 112 adults diagnosed with ADHD who were being treated with ADHD medications (primarily MPH, but also dexamphetamine and atomoxetine).
They found that at the end of that period, roughly half were still on medication, and half had discontinued treatment. There were no significant differences between the two groups in age, sex, ADHD severity, or comorbidity. The average ADHD score for the entire cohort declined to vary significantly, from a mean of 37 to a mean of 26, with less than one in a thousand odds of that being due to chance. There was also no sign of drug tolerance or a need to increase the dosage over time.
All 55 adults who discontinued treatment had taken MPH for at least part of the time. Eleven had also been treated with dexamphetamine(DEX) and 15 with atomoxetine (ATX). The average time on treatment was just under two years. Almost a third quit MPH because they perceived no beneficial effect. Since they were on average taking higher doses at discontinuation than initiation, that is unlikely to have been due to suboptimal dosage. Almost another third was discontinued for various adverse mental effects, including hyperactivity, elation, depressive moods, aggression, insomnia, fatigue, and lethargy. Another one in eleven quit when they lost contact with the prescribing physician. In the case of ATX, almost half quit because of what they perceived as adverse mental effects.
Among the 57 adults who remained on medication, four out of five reported a strong beneficial effect. Only two reported minimal or no effect. Compared with the group that discontinued, the group that remained on medication was far more likely to agree with the statements, "My quality of life has improved," and "My level of functioning has improved." Yet, as the authors caution, it is possible "that the subjects' subjective ratings contained a placebo-related mechanism in those who are compliant with the medication and pursue treatment over time." The authors reported that there were no significant differences in ADHD scores or ADHD severity between the group that quit and the group that remained on medication, even though, on average, the group that quit had been off medication for four years at follow-up.
We cannot explain why the patients who quit treatment showed similar levels of ADHD symptoms to those who continued treatment. It is possible that some patients remit symptoms over time and do not require sustained treatment. But we must keep in mind that there was a wide range of outcomes in both groups. Future work needs to find predictors of those who will do well after treatment withdrawal and those who do not.
Any decision on whether to maintain a course of medication should always weigh expected gains against adverse side effects. Short of hard evidence of continuing efficacy beyond two years, adverse events gain in relative importance. With that in mind, it is worth noting that this study reports that among those who remained on MPH, many reported side effects. More than a quarter complained of decreased appetite, one in four of dry mouth, one in five of anxiousness and increased heart rate, one in six of decreased sexual desire, one in nine of depressed mood, and one in eleven of insomnia.
This study breaks important ground in looking at the long-term effects of medication. It reaffirms findings elsewhere of the efficacy of ADHD medications. But contrary to the authors' conclusion, the data they present suggests the possibility that permanently medicating ADHD patients may not be more efficacious than discontinuation beyond a certain point, especially when balanced against adverse side effects.
But this is just one study with a relatively small sample size. This suggests a need for additional studies with larger sample sizes to pursue these questions with greater statistical reliability.
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Attention-Deficit/Hyperactivity Disorder (ADHD) in adults is commonly treated with stimulant medications such as methylphenidate and amphetamines. However, not all patients respond well to these stimulants or tolerate them effectively. For such cases, non-stimulant medications provide an alternative treatment approach.
Recent research by Brancati et al. reviews the efficacy and safety of non-stimulant medications for adult ADHD. Atomoxetine, a well-studied non-stimulant, has shown significant effectiveness in treating ADHD symptoms in adults. The review highlights the importance of considering dosage, treatment duration, safety, and the presence of psychiatric comorbidities when prescribing atomoxetine.
Additionally, certain antidepressants, including tricyclic compounds, bupropion, and viloxazine, which possess noradrenergic or dopaminergic properties, have demonstrated efficacy in managing adult ADHD. Antihypertensive medications, especially guanfacine, have also been found effective. Other medications like memantine, metadoxine, and mood stabilizers show promise, whereas treatments like galantamine, antipsychotics, and cannabinoids have not yielded positive results.
The expert opinion section of the review emphasizes that while clinical guidelines primarily recommend atomoxetine as a second-line treatment, several other non-stimulant options can be utilized to tailor treatments based on individual patient needs and comorbid conditions. Despite these advancements, the authors call for further research to develop and refine more personalized treatment strategies for adults with ADHD.
This review underscores the growing landscape of non-stimulant treatment options, offering hope for more personalized and effective management of ADHD in adults.
The Background:
Many studies have tried to determine whether exercise improves executive function in children and adolescents with ADHD, but their conclusions have not always agreed. To bring the evidence together more clearly, the research team re-analyzed the available randomized controlled trials using a statistical approach designed to handle the kinds of data common in this field.
Executive functions are skills that help us control attention and behavior. The three core components are inhibitory control (the ability to stop or override impulses), working memory (holding and manipulating information in mind), and cognitive flexibility (switching between tasks or perspectives). Because a single study often reports multiple tests that tap these different skills, one study can contribute several related results (called effect sizes). Traditional meta-analysis typically treats each effect size as independent; when they are actually correlated, that can bias the combined estimate or force reviewers to discard useful data.
To avoid those problems, the team used a three-level meta-analysis. In this model, variance in the data is separated into three sources:
(1) sampling variance: the random error in each measured effect
(2) within-study variance: differences between multiple effect sizes reported in the same study
(3) between-study variance: differences in effects from one study to another
Accounting for all three levels makes it possible to include every eligible effect size from each study, which preserves information and statistical power and reduces the risk that correlations among effect sizes will overstate results.
The Study:
The review focused on long-term exercise interventions and also tested whether certain factors might change (or moderate) the effects. These potential moderators included participant age, which executive-function subcomponent was measured, the type of exercise, how long each session lasted, the total length of the intervention, and how often sessions occurred.
To be included, studies had to be randomized controlled trials (RCTs) of children or adolescents aged 6–18 diagnosed with ADHD. RCTs randomly assign participants to an intervention or a comparison group and are considered a strong design for testing cause-and-effect. The exercise programs had to be structured and last at least six weeks. Comparison groups varied by study and could include usual care, medication, sedentary activities, health education, waiting lists, or everyday life without the specific exercise program. Fifteen studies including 658 participants met these criteria.
The Results:
The three-level meta-analysis showed that long-term exercise interventions were associated with moderate-to-strong improvements in overall executive function. When statistical outliers were removed, the result remained positive: 13 RCTs with 598 participants showed moderate improvements. In plain terms, this suggests improvements that are noticeable and meaningful on average, not just tiny changes that are unlikely to matter in daily life.
Those moderate gains appeared across all three executive-function domains (inhibitory control, working memory, and cognitive flexibility, meaning the benefits were not limited to a single cognitive skill. The authors also examined exercise type:
“Open-skill” activities, which require reacting to changing situations (for example, many team sports, martial arts sparring, or racket sports), produced moderate-to-large improvements.
“Closed-skill” activities, which are more predictable and repetitive (for example, running or stationary cycling), showed only small, non-significant improvements in this analysis.
The review also found dose-related patterns. Interventions lasting at least twelve weeks were about three times more effective than interventions of six to twelve weeks, and sessions longer than an hour were about twice as effective as shorter sessions. Benefits were largest among adolescents aged 13 and older.
These patterns suggest that longer, more intensive programs, and those that involve open-skill activities, may produce larger gains. However, the authors caution that the overall certainty of the evidence was low. “Low certainty” means that limitations in the available studies (for example, small sample sizes, variability in methods, or possible bias) make it difficult to be confident that the observed effects will hold up exactly the same way in future research. Some subgroup findings (age, intervention duration, and others) were based on only a small number of effect sizes, so those moderator results should be treated as exploratory rather than definitive.
The Take-Away:
In short, this three-level meta-analysis suggests that regular, structured exercise (particularly longer programs and open-skill activities) may help improve executive functions in children and adolescents with ADHD. The evidence is promising but not yet strong enough to be considered conclusive, and the authors recommend more, larger randomized trials to confirm specifically which types and doses of exercise are most effective. Moreover, neither this meta-analysis or others show that exercise can replace standard treatments for reducing the core symptoms of ADHD (inattention, hyperactivity, impulsivity).
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When a patient sits down in an examination room today, their physician is rarely the first voice they have heard regarding their symptoms. More often, an algorithm got there first.
According to a nationwide survey by The Physicians Foundation conducted with Medscape, medical misinformation is no longer a peripheral nuisance; it is a daily clinical crisis. Nearly all surveyed physicians (99.9%) reported that their patients had been influenced by medical misinformation over the past year.
While misinformation affects every discipline from oncology to cardiology, few conditions sit as squarely in the algorithmic crosshairs as ADHD. From viral 30-second video clips trivializing complex executive dysfunction to predatory wellness campaigns attacking evidence-based medications, the attack on evidence directly threatens the well-being of children and adults living with ADHD.
Key Findings from The Physicians Foundation
The survey, which captured perspectives from over 1,000 practicing physicians, paints a sobering picture of how unverified information disrupts modern medicine:
The challenge is especially acute in communities already facing systemic healthcare hurdles:
As the survey illustrates, 38% of rural physicians encounter "a great deal" of health misinformation, far exceeding their suburban (21%) and urban (25%) peers. In rural and underserved regions, where access to developmental pediatricians and psychiatrists is already scarce, online narratives frequently fill the void left by provider shortages.
Why ADHD Is Ground Zero for Health Misinformation
Despite decades of neurobiological research confirming its validity, ADHD remains uniquely vulnerable to digital distortions in three distinct ways:
1. The Dueling Traps: "Life Hack" Trivialization vs. Denialism
Social media platforms host billions of views under ADHD-related tags. While digital awareness has helped destigmatize mental health, it frequently collapses nuanced clinical criteria into broad, relatable personality traits such as zoning out during a boring meeting, misplacing keys, or feeling restless.
This creates two opposing misinformation hazards:
2. Medication Stigma and Treatment Nonadherence
The survey found that 49% of doctors frequently encounter medication nonadherence and 45% face treatment refusal due to misinformation.
In ADHD care, this finding is acutely visible around stimulant pharmacotherapy. First-line stimulant medications have high response rates and extensive safety profiles spanning decades. Yet online narratives persistently frame them as dangerous narcotics, accusing parents of "drugging their children" or claiming medications permanently alter a child's brain.
Terrified parents frequently delay initiating care or discontinue effective regimens without clinical oversight, turning instead to unproven, expensive alternative supplements, unverified nootropics, or restrictive elimination diets.
3. Escalating Anxiety and Parental Guilt
With 66% of physicians observing increased patient anxiety driven by online health claims, the emotional toll on families cannot be overstated. Parents of newly diagnosed children are inundated with contradictory advice: one post warns that failing to medicate guarantees academic failure, while another claims that medicating guarantees addiction.
Adults navigating a new diagnosis experience similar distress, second-guessing their lived experiences and feeling deep shame over their executive dysfunction.
4. The 15-Minute Primary Care Bottleneck
Because pediatricians and family physicians handle most ADHD diagnoses and management, the survey’s warning that 70% of primary care providers feel hamstrung by misinformation hits ADHD patients first.
Deconstructing a viral video, explaining the difference between therapeutic stimulant dosing and substance misuse, and addressing years of internalized stigma takes time. In a standard 15-to-20-minute primary care visit, providers are forced to choose between rushing through diagnostic assessments or leaving patients' misinformed fears unaddressed.
Rebuilding the Partnership: Steps for Patients, Families, and Providers
Addressing the erosion of trust requires practical, collaborative shifts from both sides of the examination table:
For Patients and Caregivers
For Healthcare Providers and Systems
Medical misinformation thrives in the gap between a patient's vulnerability and the clinical system's time constraints. By recognizing how digital noise distorts ADHD, patients and clinicians can work together to replace viral anxiety with evidence-based care.
The Background:
Adults with ADHD often struggle more at work than their peers without ADHD. They tend to underperform on job tasks, advance less in their careers, miss more workdays, and face higher rates of unemployment. Research from several countries, including Japan, points to two main channels through which ADHD erodes workplace productivity: absenteeism, or missing work entirely, and presenteeism, showing up but performing below one’s usual capacity. Both problems typically trace back to ADHD’s core symptoms: difficulty sustaining attention, managing time, staying organized, and navigating relationships with coworkers and supervisors.
Stigma compounds these challenges. Employers and the public often have limited understanding of how ADHD manifests in adults, which can translate into unfair treatment or diminished job opportunities. That fear of judgment, in turn, discourages some people from seeking a psychiatric evaluation in the first place, delaying diagnosis and treatment, and with it, delaying access to support that could improve both their work performance and daily functioning.
Japan does offer medical care and workplace support for adults with ADHD. Options include social skills training, which teaches practical strategies for communication and collaboration; self-reliance support programs that help with daily living and job management; and, in more severe cases, a disability pension for those unable to work. Still, it remains unclear whether these employment-support services are robust enough to help people who want to work actually secure and hold onto steady jobs.
The impact of ADHD extends beyond the individual diagnosed. Supporting a family member with ADHD can be emotionally and logistically demanding, often cutting into a caregiver’s own capacity to work and earn, meaning that the economic toll of ADHD ripples outward.
The Research:
Most prior research on the economic costs of ADHD, in both children and adults, has come from the United States and Europe, focusing on medical expenses, lost productivity, and social support spending. Until recently, no one had attempted a comparable estimate for adult ADHD in Japan or elsewhere in Asia.
To address that gap, a Japanese research team conducted a cross-sectional observational study (meaning they gathered data at a single point in time and examined existing patterns rather than testing an intervention). They drew on three sources: a retrospective review of medical insurance claims, a web-based survey of affected individuals, and official government statistics. Combining these, they estimated annual costs from a societal perspective, accounting for medical expenses, lost work productivity, and government welfare spending, as well as productivity losses among family caregivers.
The claims analysis relied on JMDC, a nationwide database of insurance receipts and medical examination records spanning multiple health insurers and covering 14 million residents. Within it, the researchers identified 30,730 adult outpatients diagnosed with ADHD.
The Results:
Annual medical costs per adult with ADHD (combining outpatient visits and medication) averaged 284,000 yen (about $1,750). Scaling this figure to match the age and sex distribution of Japan’s adult population produced a nationwide estimate of 74 billion yen (about $455 million).
A separate web-based survey found that, after statistical matching, nearly half of adults with ADHD received a disability pension, yielding a nationwide estimate of 95 billion yen (about $585 million) in ADHD-related pension payments. Including public employment support services, total social welfare spending reached 390 billion yen (about $2.4 billion).
Workplace productivity losses were substantial as well. With an unemployment rate more than four percentage points higher than the general population, unemployment-related losses among adults with ADHD totaled an estimated 50 billion yen. Lower average incomes among those employed accounted for a further 315 billion yen. Once absenteeism and presenteeism were factored in, total productivity losses reached 570 billion yen (about $3.5 billion).
Family members bore a comparable burden: productivity losses among adult relatives of people with ADHD were estimated at 540 billion yen (about $3.3 billion).
Taken together, these figures point to a nationwide socioeconomic burden of 1.6 trillion yen (roughly $11 billion), equivalent to nearly $30,000 per adult with ADHD.
The Take-Away:
“This study, the first estimate of the annual socioeconomic burden of adult ADHD in Japan, underscores the necessity of providing appropriate support to adult patients with ADHD and their families and the prevention of comorbidities,” the research team concluded. “In particular, measures to support participation in the workplace to improve patients’ quality of life and reduce the social and economic burden should be explored. Furthermore, it is hoped that estimating the annual socioeconomic burden of adult ADHD will help clarify policy priorities in Japan.”
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