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September 14, 2023
Taiwan's single-payer National Health Insurance system encompasses its entire population, and it's National Health Insurance Research Database tracks all medical claims in the system. That makes it easy to conduct nationwide population studies.
Two Taiwanese research teams availed themselves of that database to explore in-depth a surprising relationship between the birth month of children and rates of ADHD diagnosis.
In principle, the two should be unrelated. The likelihood of diagnosis should be the same regardless of the month a child is born. But the data are clear that this is not so. Children born late in summer are the most likely to be diagnosed with ADHD, and those in autumn are the least likely.
Using a nationwide database of over 29 million persons, one of the teams (Hsu et al.) found that children born in April were 6% more likely to be diagnosed with ADHD than the year-round mean, those in May 12% more likely, those in June 20% more likely, and those in July and August well over 25% more likely.
Conversely, children born in September were 19% less likely to be diagnosed with ADHD than the year-round mean, followed by a gradual increase in likelihood with each succeeding month until the following September.
The second team (Chen et al.) analyzed some 9.5 million children and adolescents in the same reserch database, and found that those born in August were 67% more likely to be diagnosed with ADHD than those born in September, after adjusting for age, sex, residence, and income. August births were also almost twice as likely (80% more likely) as September births to be on long-term treatment with ADHD medications.
The first team also performed a meta-analysis of eleven studies with a combined total of over 580,000 participants in North America (the U.S. and Canada), Europe (U.K., Germany, Norway, Sweden, Denmark), Asia (China, Taiwan, South Korea), and Oceania (Australia). Children born in the summer (June through August) were 13% more likely to be diagnosed with ADHD than the year-round mean, whereas those born in autumn were 13% less likely to be diagnosed with ADHD. This confirms that this pattern is not confined to Taiwan. It is worldwide.
Note carefully that the sharp discontinuity between August and September corresponds with the break-of point that decides which children get assigned to which school class. Anyone who turns a certain age by the start of the school year in September is included in the class associated with that age, whereas those turning the same age later are held back in the following class. That means that in any given class, those born in September are the oldest children and those born in August the youngest.
As signaled earlier, the likelihood of an ADHD diagnosis should be independent of something as obviously arbitrary as a birth month. That suggests there may be an unconscious bias trending against younger students when it comes to diagnosis.
Chen et al. concluded, "The effect of relative age on diagnoses and prescriptions was determined to last from childhood to adolescence but attenuated with age. Relative age is an indicator of brain maturity in cognition, behavior, and emotion and may thus play a critical role in the likelihood of being diagnosed as having childhood mental disorders and subsequently being prescribed psychotropic medication. Therefore, clinicians should consider the relative age effect in the childhood mental health care context."
Mu-Hong Chen, Kai-Lin Huang, Ju-Wei Hsu, Shih-Jen Tsai, Tung-Ping Su, Tzeng-Ji Chen, Ya-Mei Bai, "Effect of relative age on childhood mental health: A cohort of 9,548,393 children and adolescents," Acta PsychiatricaScandinavica (2021), online ahead of print, https://doi.org/10.1111/acps.13327.
Chih-Wei Hsu, Ping-Tao Tseng, Yu-Kang Tu, Pao-Yen Lin, Chi-Fa Hung, Chih-Sung Liang, Yun-Yu Hsieh, Yao-Hsu Yang, Liang-Jen Wang, Hung-YuKao, "Month of birth and mental disorders: A population-based study and validation using global meta-analysis," Acta Psychiatrica Scandinavica (2021), online ahead of print, https://doi.org/10.1111/acps.13313.
Executive functions are the mental processes that allow us to plan, adapt, and follow through. This encompasses working memory, inhibitory control, cognitive flexibility, goal-directed planning, and problem-solving. In people with ADHD, weaknesses in these areas compound the disorder's core symptoms, making it substantially harder to manage complex, real-world demands.
Background:
Medication remains the frontline clinical response. Stimulant medications can meaningfully reduce both executive function deficits and ADHD symptoms, and are often combined with behavioral or psychological therapies for better overall outcomes.
Medication, however, is not entirely without risk of side effects. These risks have spurred interest in new, non-pharmacological alternatives that target the same neural pathways. One of these new therapies is Computerized Cognitive Remediation Therapy (CCRT). This therapy uses digital programs delivered via computer, tablet, or smartphone that train attention, memory, and inhibitory control through structured cognitive exercises. A key feature of many CCRT platforms is adaptive difficulty: tasks adjust in real time to match the child’s current ability, keeping training both challenging and engaging.
The Study:
Despite this promise, the evidence base in younger populations has been limited. This meta-analysis pooled results from randomized controlled trials enrolling participants under 18 who either carried an ADHD diagnosis or scored above the threshold on a validated rating scale. Comparators included no treatment (waitlist), placebo (pharmacological or psychological), or treatment as usual. The primary outcomes (overall executive function and clinical symptom severity) were assessed via questionnaires and neuropsychological testing. Studies including participants with comorbid autism, tic disorders, epilepsy, or other psychiatric conditions were excluded.
The findings were informative, but overall results were mixed. CCRT produced a small but statistically meaningful reduction in inattention symptoms across 13 studies (885 participants), with consistent results across individual trials and no evidence of publication bias. However, it had no detectable effect on hyperactivity and impulsivity (12 studies, 833 participants) or on total ADHD symptom burden (10 studies, 731 participants).
The picture was more encouraging for executive function. Nine studies (500 participants) showed small overall improvements, with specific gains in working memory (454 participants), inhibitory control (428 participants), and planning (6 studies, 335 participants). Emotional control showed no significant change (5 studies, 265 participants), nor did cognitive flexibility (4 studies, 189 participants).
The Take-Away:
Taken together, these results are modest rather than transformative, but context matters. CCRT is low-cost, digitally scalable, and carries negligible side effects. For a population where medication often comes with a significant burden of adverse reactions, even small, reliable improvements in executive function represent a meaningful clinical option.
The evidence positions CCRT not as a replacement for established treatments, but as a practical and well-tolerated addition to the therapeutic toolkit for children and adolescents with ADHD.
Methylphenidate is an effective treatment for ADHD in adults who also have bipolar disorder (BD), but it carries a potential risk of triggering manic episodes. Current guidelines therefore recommend using it only alongside mood-stabilizing medication. A new study using French nationwide claims data sought to test and extend those recommendations with greater statistical power than previous research.
The study built on findings by Viktorin et al. (2017), who observed that adults with BD not taking mood stabilizers had more than a sixfold higher risk of manic events (defined as hospitalization for mania or a new antimanic prescription) within six months of starting methylphenidate. Patients on mood-stabilizing treatment, by contrast, showed nearly half the baseline risk in the first three months. Those findings were limited, however, by small event counts (fewer than 61 manic episodes) and an effect that did not persist beyond the initial three-month window.
To build on this, researchers drew on the French National Health Data System (which is a claims database covering more than 60 million people) spanning 2008 to 2024. The final sample included 6,022 adults with BD (56% women) who had started methylphenidate. Using a self-controlled design, the study compared each patient's rate of manic events in the six months before their first methylphenidate prescription with the rate in the six months after, effectively eliminating stable individual differences as a confound.
Patients were classified as receiving continuous mood-stabilizing treatment if they had been dispensed at least two courses of specific antipsychotics (aripiprazole, olanzapine, or quetiapine) or mood stabilizers (lithium or valproate) in the nine months before starting methylphenidate, including at least one dispensation in the final six months of that window.
The results largely confirmed the earlier findings. Among the 2,745 patients not on mood stabilizers, the rate of inpatient mania diagnosis was 5.1 times higher in the first three months after starting methylphenidate, though this elevation fell to a non-significant level over the subsequent three months. Patients receiving continuous mood-stabilizing treatment showed no statistically significant change in mania risk across the full six-month post-initiation period. A formulation-specific pattern also emerged: patients without mood-stabilizing treatment had a 2.5-fold higher risk associated with extended-release methylphenidate, while no significant risk increase was seen with the immediate-release formulation or in treated patients regardless of formulation.
The authors conclude that methylphenidate at doses below 30 mg does not appear to elevate manic relapse risk when prescribed alongside mood stabilizers. The elevated risk seen in untreated patients, particularly with extended-release formulations, must be interpreted cautiously, given limited statistical power and the likelihood that it partly reflects the natural fluctuation of manic relapse over time. The authors flag this as an inherent limitation of self-controlled survival analyses when studying drug-induced mania, where temporal trends in the underlying condition can be difficult to disentangle from treatment effects.
The FDA has approved a new once-daily pill called centanafadine (trade name SIMTRIYO®). Approved for adults and kids aged 6 and older (weighing at least 44 lbs / 20 kg), centanafadine is a new category of ADHD treatment that aims to give fast results with fewer of the downsides of traditional stimulants.
To understand why centanafadine is unique among medications for ADHD, it helps to look at how ADHD brain chemistry works:
Stimulants like Ritalin and Adderall work mainly in the dopamine system. Nonstimulants like atomoxetine, viloxazine, clonidine and guanfacine work mainly on the norepinephrine system. Centanafadine is the first drug in a new class called NDSRIs (Norepinephrine, Dopamine, and Serotonin Reuptake Inhibitors). We can describe its effects as follows:
What Did Clinical Trials Show?
The FDA approved centanafadine based on studies involving thousands of adults, teens, and children. Here are the key findings:
Centanafadine showed some improvement in ADHD symptoms within the very first week of taking it although a full effect takes about six weeks.
In adult trials, taking 200 mg or 400 mg daily led to significant improvements in real-world skills:
In trials with children (ages 6–12) and teens (ages 13–17), centanafadine significantly reduced core ADHD symptoms like hyperactivity, impulsivity, and lack of focus compared to a placebo.
About 30% to 40% of adults with ADHD also suffer from anxiety. Traditional stimulants can make anxiety worse. In a trial specifically designed for adults dealing with both ADHD and anxiety, centanafadine effectively treated ADHD symptoms without firing up their anxiety, which might be due to its serotonin boost.
Does Centanafadine have Side Effects?
While Centanafadine was well-tolerated by most people in studies, like any prescription medication, it comes with important safety guidelines.
Prescribing Warnings:
Common Side Effects:
Other Warnings:
The Bottom Line
Overall, centanafadine is a new step forward in how we treat ADHD. Because it acts differently in the brain than traditional treatments, patients who struggle with stimulant-related anxiety or side effects may find it useful to explore with their doctor.
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