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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."
Exercise has attracted growing attention as an intervention for ADHD. As a potential treatment option for ADHD, it is, of course, highly appealing because it can be low- to no-cost, widely accessible, and free of the side effects that can accompany medication. From previous studies, we know that certain types of exercise may be more effective than others, but do we actually know enough for clinicians to prescribe physical activity as a treatment for ADHD?
The First Study: Effects on Core ADHD Symptoms
Despite encouraging findings in individual studies, researchers have lacked clear guidance on which types of exercise work best, at what intensity, and for how long. A meta-analysis by Chen et al. set out to address this by pooling data from 20 randomized controlled trials (RCTs) involving 841 children and adolescents aged 4–18, all of which compared exercise interventions against non-exercising control groups.
The results were cautiously optimistic. Across standardized symptom scales, exercise produced a small improvement in ADHD symptoms overall. Objective cognitive tests showed a moderate improvement. Emotional and behavioral outcomes, however, showed no significant change.
To understand what was driving differences between studies, the researchers broke results down by exercise type. Therapeutic and alternative exercises (targeted movements and specific techniques such as those prescribed by physical therapists) were associated with moderate symptom improvements. Mind-body practices (such as yoga or tai chi) showed small-to-moderate gains. Conventional aerobic exercise yielded smaller effects, while skill-based competitive sports showed no measurable benefit. Notably, the variability between individual studies remained high throughout, meaning these categories should be interpreted with some caution.
Results:
The authors recommend that clinicians and parents consider incorporating therapeutic or alternative exercise sessions twice a week, each lasting 60–90 minutes, as a supplemental strategy alongside existing ADHD treatment. They stop short of calling this definitive, noting that future research should clarify how exercise produces its effects and how it might best be combined with medication or behavioral therapy.
The Second Study: Effects on Inhibitory Control
A second meta-analysis, by Zhang et al., zoomed in on a specific and particularly relevant cognitive challenge in ADHD: inhibitory control. Inhibitory control refers to the ability to suppress impulsive responses and tune out irrelevant distractions. This capacity underlies much of the restlessness, interrupting, and difficulty staying on task that characterize the condition.
This analysis drew on 34 studies with over 1,300 participants spanning all age groups, making it broader in scope than the Chen et al. review. Overall, exercise was associated with a moderate improvement in inhibitory control. When the analysis was restricted to RCTs alone, this finding held up. When studies with a high risk of bias were excluded, however, the effect size dropped to small-to-moderate.
One notable null result: three studies that used EEG to measure brain activity during inhibitory tasks found no significant effects on the neural signatures most closely tied to this process. This suggests exercise may influence behavior without necessarily changing the underlying brain mechanisms researchers expected, or that current methods aren't yet sensitive enough to detect such changes.
The dosing question produced some of the more practically useful findings. Single exercise sessions yielded only borderline small improvements. Sustained exercise programs, by contrast, showed moderate improvements, and programs with sessions three times per week produced large gains and had the strongest effect between the two meta-analyses. Exercise intensity and total program duration, perhaps interestingly, were not significant factors.
Results:
The authors are measured in their conclusions: exercise shows a real but modest benefit for inhibitory control, and frequency appears to matter more than intensity. They caution against overstating the case for exercise as treatment for ADHD overall, as it did not significantly affect hyperactivity or impulsivity as standalone outcomes, and its neural effects remain unclear.
The Broader Picture :
Ultimately, these two meta-analyses support exercise as a meaningful supplemental intervention for ADHD, particularly for attention and cognitive control, while urging realistic expectations. Neither suggests exercise should replace established treatments. Both are limited by high variability across the underlying studies, and both call for better-designed research to sharpen the guidance available to clinicians and families.
Boredom is more than just feeling restless or under-stimulated. It’s a negative emotional state that arises when activities feel meaningless or dull and, for those with ADHD, this negative emotional state might be markedly more intense. Researchers increasingly view boredom as functional: an internal signal pushing people to seek more rewarding and meaningful experiences. But for some, that signal becomes chronic and overwhelming.
People who are highly prone to boredom face a range of psychological and behavioral consequences, including anxiety, depression, difficulty identifying their own emotions (alexithymia), impulsivity, and physical complaints. These struggles often surface in harmful behaviors: overeating, substance use, compulsive internet use, and gambling.
For people with ADHD, boredom can cross into genuine distress. Many describe it as “torture” or “an itchy coat you can’t scratch”, language that conveys not mild discomfort but an urgent, almost unbearable need to escape. This makes sense given that ADHD involves core difficulties with attention, arousal regulation, and motivation, all of which make sustained engagement harder and boredom far more likely.
The Study:
A recent meta-analysis of 18 studies involving more than 22,000 participants confirmed a moderately strong and consistent positive association (an overall effect size of r = 0.40) between ADHD and self-reported boredom. All but one study found significant results, and there was no evidence of publication bias.
“While the relationship between ADHD and boredom may seem obvious,” the authors state, “this has paradoxically led to the phenomenon being understudied.”
Despite how significant this connection appears to be, the researchers noted it has attracted surprisingly little scientific attention; a gap they attribute to a widespread assumption that boredom in ADHD is simply a byproduct of inattention or impulsivity, and therefore not worth studying on its own terms. They push back on that view, arguing that boredom may be a more fundamental part of the ADHD experience: a bridge between atypical brain function and the behavioral, emotional, and cognitive difficulties that shape long-term outcomes.
The Take-Away:
Ultimately, addressing the profound boredom experienced by individuals with ADHD requires a multifaceted approach that goes beyond simply treating inattention. Researchers emphasize the need for rigorous studies to determine if stimulant medications actively reduce this intense boredom by repairing underlying brain mechanisms, rather than just as a side effect of improved focus. Beyond medication, tailored psychological therapies may offer promise; psychoeducation can help individuals reframe boredom as a biological signal rather than a personal failure or character flaw.
Additionally, another approach suggests that rather than solely focusing on treating the individual, systemic issues must be addressed, such as the effects of low-stimulation environments. For example, prioritizing a better "person-environment fit" through smaller class sizes, flexible academic pacing, and/or offering highly stimulating, novel tasks, schools and workplaces can offer meaningful relief from the chronic distress of ADHD-related boredom.
A new study from Japan suggests that infants born with craniosynostosis are significantly more likely to be diagnosed with ADHD later in childhood. Craniosynostosis is a condition in which the bony plates of the skull fuse prematurely, leading to increased intracranial pressure.
The Background:
Craniosynostosis affects roughly one in every 2,000 births. When the skull’s natural seams close prematurely, it can restrict brain growth and increase intracranial pressure, potentially reducing blood flow to the brain. Because the condition is relatively rare, it has been difficult to study at scale until now.
The Study:
To overcome this, researchers tapped into a large Japanese insurance database compiled by JMDC, Inc., which holds records on around 20 million people, or about 15% of Japan’s population. Drawing on two decades of data, the team tracked over 338,000 mother-child pairs. Children with related genetic syndromes or chromosomal conditions such as Down syndrome were excluded to keep the focus on craniosynostosis itself.
Of the children studied, around 1,145 had craniosynostosis, and 7,325 were diagnosed with ADHD. After accounting for factors like sex, birth year, maternal age, mental health history, pregnancy infections, and birth complications, children with craniosynostosis were found to have roughly 2.4 times the risk of a subsequent ADHD diagnosis compared to those without it.
To test whether shared family genetics or home environment might be driving the association rather than the skull condition itself, the researchers conducted a separate analysis among siblings. The elevated risk remained at 2.2 times. The consistency of the finding across both analyses strengthens the case for a genuine biological link.
The Results:
The results point to raised intracranial pressure and restricted cerebral blood flow as plausible mechanisms, though the study’s observational design means causation cannot be confirmed. Ultimately, these findings highlight the need for proactive, long-term care strategies for those born with craniosynostosis. By establishing a solid link between premature skull fusion and a significantly higher risk of ADHD, the research demonstrates that medical care for this condition should not end once the skull's physical structure is addressed.
The Takeaway:
Pediatricians, neurologists, and parents can use this data to implement early, routine behavioral and developmental screening for these children as they grow. This additional support would ensure that those who do develop ADHD can receive timely interventions, educational aids, and therapies, ultimately improving their long-term developmental outcomes.
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