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July 25, 2024
Dasotraline is a serotonin-norepinephrine-dopamine reuptake inhibitor (SNDRI) that had been under development by Sunovion for treating ADHD and binge eating disorder.
An Indian research team conducted a systematic search of the peer-reviewed medical literature to perform meta-analyses of the quantitative outcomes of clinical trials.
Meta-analysis of five double-blinded randomized clinical trials (RCTs) with a combined total of 1,498 participants reported a small-to-medium effect size reduction in ADHD symptoms in patients given dasotraline as opposed to those given placebo.
There were, however, strong indications of publication bias. Using the trim-and-fill procedure to correct for that bias yielded a small effect size reduction in ADHD symptoms in patients given dasotraline compared with those given placebo.
Insomnia were more than four times more frequent among patients given dasotraline than among those given placebo. There was no evidence of the frequency of insomnia being dose-dependent.
Similarly, patients given dasotraline were more than four times more likely to report decreased appetite than those receiving placebo. In this case, however, the effect was clearly dose-dependent, rising from 3x for 2mg to 4x for 4mg to 5x for 6mg and almost 8x for 8mg.
The authors concluded, “dasotraline can reduce the core symptoms of ADHD, that is, hyperactivity/impulsivity and inattentiveness, leading to an overall improvement of ADHD compared to placebo. Dasotraline can also improve clinician-determined patients’ global functioning compared to the placebo. The most common adverse drug reactions related to dasotraline were insomnia and decreased appetite. However, to fill the knowledge gap, multicentric randomized active-controlled clinical trials are warranted in this domain for a successful translation into clinical practice.”
Weighing these less than impressive initial results against the cost of further RCTs, Sunovion withdrew its application for approval by the Food and Drug Administration, stating, “while Sunovion considers dasotraline to be a promising, novel treatment for binge eating disorder and ADHD, we believe that further clinical studies would be needed to support a regulatory approval for dasotraline in these indications.”
Rituparna Maiti, Archana Mishra, Monalisa Jena, Shampa Maji, Milan Padhan, Biswa R. Mishra, “Efficacy and safety of dasotraline in attention‐deficit hyperactivity disorder: A systematic review and meta‐analysis,” Indian Journal of Psychiatry (2024), https://doi.org/10.4103/indianjpsychiatry.indianjpsychiatry_3_24.
Brian Park, “Dasotraline Development for ADHD, Binge Eating Disorder Halted, NDAs Withdrawn,” Medica Professionals Reference, May 14, 2020, https://www.empr.com/home/news/drugs-in-the-pipeline/sunovion-withdraws-nda-dasotraline-development-binge-eating-adhd/.
Child abuse includes any of the following inflicted on a minor under 18 years old: physical or emotional harm, sexual abuse, or neglect.
It is known to be associated with environmental factors such as poverty, parents or neighbors with a history of violence, and gender inequality.
Chronic mental disorders in minors are also associated with child abuse. To what extent, if any, might that be true of ADHD?
Taiwan has a single-payer national health insurance system that covers more than 99.6% of all residents, enabling nationwide population studies.
A local research team used data from almost two million Taiwanese in their country’s National Health Insurance Research Database (NHIRD) spanning 15 years (2000-2015) to carry out a matched-cohort study.
All diagnoses of ADHD were made by board-certified specialists such as psychiatrists, pediatricians, neurologists, or physiatrists with a specialty in child and adolescent development.
3,540 children and adolescents between 6 and 18 years old with a diagnosis of ADHD were matched on a one-to-three basis with 10,620 peers from the NHIRD without an ADHD diagnosis.
The team adjusted for age, gender, location of residence (Northern, Central, Southern, and Eastern Taiwan), urbanization level of residence, level of hospitals as medical centers, and monthly insured premium. They further adjusted for comorbid conditions: intellectual disability, autistic disorder/pervasive developmental disorder, conduct disorder (CD)/oppositional defiant disorder (ODD), other developmental disorders, childhood emotional disorder, Tourette syndrome/tics disorders, and involuntary urination and defecation.
Overall, children and adolescents with an ADHD diagnosis were 1.8 times as likely to be abused as those without an ADHD diagnosis.
Unmedicated children and adolescents with an ADHD diagnosis were three times more likely to be abused. ADHD medication cut that risk in half.
That held true whether the medication used was methylphenidate or atomoxetine. Methylphenidate appeared to be slightly more effective than atomoxetine, and the combination of methylphenidate and atomoxetine slightly more effective yet, but these differences were not statistically significant.
The team concluded, “The results support that pharmacotherapy may attenuate the risk of child abuse in ADHD patients.”
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 ..."
A team from Harvard Medical School and Massachusetts General Hospital conducted a six-week open-label trial of liquid-formulation extended-release methylphenidate (MPH-ER) to treat ADHD in adults with high-functioning autism spectrum disorder (HF-ASD). ASD is a lifelong disorder with deficits in social communication and interaction and restricted, repetitive behaviors. Roughly half of those diagnosed with ASD also are diagnosed with ADHD.
This was the first stimulant trial in adults with both ASD and ADHD. There were twelve males and three female participants, all with moderate to severe ADHD, and in their twenties, with IQ scores of at least 85.
The use of a liquid formulation enabled doses to be raised very gradually, starting with a daily dose of 5 mg(1mL) and titrating up to 60 mg over the first three weeks, then maintaining that level through the sixth week. Participants were reevaluated for ADHD symptoms every week during the six-week trial. The severity of ASD was assessed at the start, midpoint, and conclusion of the trial, as were other psychiatric symptoms.
Before the trial, researchers agreed on a combination of targets on two clinician-rated scoring systems that would have to be reached for treatment to be considered successful. One is a score of 2 or less on the CGI-S, a measure of illness severity, with scores ranging from 1 (normal, not at all ill) to 7 (most extremely ill). The other is a reduction of at least 30 percent in the AIS RS score, which combines each of 18 symptoms of ADHD on a severity grid (0=not present; 3=severe; overall minimum score: 0; overall maximum score: 54).
After the trial, twelve of the fifteen patients (80 percent) met the preset conditions for success. Fully fourteen (93 percent) saw a ≥ 30 percent reduction in their AISRS score, while twelve scored ≤ 2 on illness severity.
However, when using the patient-rated ASRS scoring system, only five (33 percent) saw a ≥ 30 percent reduction in ADHD severity.
Thirteen participants (87percent) reported at least one adverse event, and nine (60 percent) reported two or more. One reported a serious adverse event (attempted suicide) in a patient with multiple prior attempts. Because the attempt was not deemed due to medication, they continued and completed the trial. Seven participants experienced titration-limiting adverse events (headaches, palpitations, jaw pain, and insomnia). Headache was most frequent (53%), followed by insomnia and anxiety(33% each), and decreased appetite (27%).
During the trial, weight significantly decreased, while pulse significantly increased. There were no significant differences in other vital and cardiovascular measurements.
The authors concluded, "this OLT of short-term MPH-ER therapy documents that acute treatment with MPH-ER in young adults with ASD was associated with significant improvement in ADHD symptoms, mirroring the typically-expected magnitude of response observed in adults with only ADHD. Treatment with MPH-ER was well-tolerated, though associated with a higher than expected frequency of adverse events."
They also cautioned, "The results of this study need to be considered in light of some methodological limitations. This was an open-label study; therefore, assessments were not blind to treatment. We did not employ a placebo control group and, therefore, cannot separate the effects of treatment from time or placebo effects. ... firmer conclusions regarding the safety and efficacy of MPH-ER for the treatment of ADHD in HF-ASD populations await results from larger, randomized, placebo-controlled clinical trials."
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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