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March 5, 2022
Persons with ADHD have known to have high rates of psychiatric comorbidities. There is also growing evidence of somatic (non-psychiatric) comorbid disorders among youths with ADHD, such as metabolic syndrome (which can lead to type 2 diabetes) and chronic inflammation (such as asthma and allergic rhinitis). Much less is known, however, about comorbid conditions in adults with ADHD.
An international team of researchers looked for indicators of comorbid conditions in a nationwide cohort study using Swedish national registers. The target population was Swedish residents between the ages of 18 and 64 in 2013 and more specifically those who had been prescribed ADHD medication. They identified over 41,000 individuals who met these criteria, including over twenty thousand young adults aged 18-29 years, over sixteen thousand middle-aged adults aged 30-49 years, and over four thousand older adults aged 50-64. The remainder of the overall cohort were used as controls.
Young adults receiving ADHD medications were four times as likely to also be receiving somatic medications, and older adults were seven times as likely. The highest rate of co-medication -roughly five times more frequent than among controls - was for respiratory system medications. The second most common was for alimentary tract and metabolic system medications, with odds over four times higher than for controls. Cardiovascular system medications were the next most common, with odds among young adults receiving ADHD medications over four times those of controls, though reducing with age to being twice as common in older adults with ADHD. Patterns were similar among men and women.
Adults receiving ADHD medications were far more likely to also be receiving other psychotropic medications. Middle-aged adults were 21 times as likely to be dispensed such medications as controls, older adults eighteen times more likely, and younger adults fifteen times more likely.
For young adults prescribed ADHD medications, the most prevalent co-prescriptions were for addictive disorders, which were dispensed at over 26 times the rate for controls. For middle-aged and older adults, on the other hand, the most prevalent co-prescriptions were for antipsychotics, which were likewise dispensed at over 26 times the rate for controls. Results remained consistent for individuals who had an ADHD diagnosis in addition to an ADHD prescription.
In addition, individuals receiving ADHD medications were also on average taking more types of prescriptions, rising from 2.5 classes of medications at age 18 to five classes at age 64. For controls, the equivalent numbers were 0.9 types of medications at age 18, rising to 2.7 at age 64.
Looking at specific somatic medications prescribed, those for respiratory conditions were ones typically prescribed for asthma and allergic reactions, reinforcing a previously known association. Insulin preparations also had high rates of co-prescription, again further confirming the known association with obesity and diabetes.
On the other hand, the most commonly dispensed alimentary tract and metabolic system medications included proton pump inhibitors, typically prescribed for gastric/duodenal ulcers and gastroesophageal reflux disease. Sodium fluoride, prescribed to prevent dental caries, was also prominent. Neither of these is an established association and warrants further exploration.
Turning to psychotropic medications, the most frequent prescriptions were with drugs used to treat addictive disorders and with antipsychotics. Rates of opioid co-prescription were also notably high, a source of concern given the higher proclivity of persons with ADHD to substance use disorders.
Le Zhang, AndreasReif, Ebba Du Rietz, Tyra Lagerberg, Agnieszka Butwicka, Brian M. D'Onofrio, Kristina Johnell, Nancy L. Pedersen, Henrik Larsson, and Zheng Chang, "Comedicationand Polypharmacy With ADHD Medications in Adults: A Swedish Nationwide Study," Journal of Attention Disorders (2020),https://doi.org/10.1177/1087054720923725.
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.
A landmark nationwide study from South Korea has uncovered a significant link between prenatal exposure to air pollution — specifically nitrogen dioxide (NO2) — and an increased risk of ADHD in children.
While researchers have long suspected that air pollutants interfere with fetal brain development through inflammation and oxidative stress, this study is one of the largest and most comprehensive of its kind, following nearly 1.5 million births for up to 13 years.
Why South Korea?
South Korea provided a unique countrywide “laboratory” for this research due to two key infrastructure strengths:
Key Findings: The “Smoking Gun” of NO2
While the study looked at several pollutants, nitrogen dioxide — a byproduct of fossil fuel combustion in cars and power plants — emerged as the primary concern.
Pollutant
Association with ADHD Risk
Nitrogen Dioxide (NO2)
Strongest Link: Every 1-ppb (part-per-billion) increase in exposure linked to a 22% rise in risk.
Sulfur Dioxide (SO2)
Minimal Link: Only a slight 4% increase per ppb.
Ozone (O3) carbon monoxide (CO), & particulates
No significant association was found.
The scale of the NO2 risk is particularly striking. Over the typical range of exposure levels found in the study (an interquartile range of 13 ppb), the data suggest a threefold increase in ADHD risk for children in the highest-exposure groups compared to the lowest.
Accounting for Other Factors
To ensure the results weren’t skewed by other variables, the researchers controlled for a wide range of confounders including:
The authors emphasized the strong association between maternal nitrogen dioxide exposure and ADHD, while also noting the small but significant association with sulfur dioxide.
The Take-Away: A New Frontier for Public Health
Historically, air quality laws have been designed to protect our lungs and hearts. However, this study adds to a growing body of evidence suggesting that the brain is likewise vulnerable.
In a commentary on the findings, expert George Ayoub argued that “neurodevelopment should be explicitly considered” when governments perform cost-benefit analyses on air quality regulation. My view is a bit different. The association is intriguing but the study does not establish cause and effect. Many statistically significant environmental risk associations for neurodevelopmental disorders have disappeared after controlling for maternal risk for ADHD. I hope this research team will do those analyses if feasible.
Executive functions (EFs) are the cognitive control systems that allow people to pursue goals, make decisions, and adapt to changing circumstances. Researchers generally break them into three overlapping capacities: working memory (holding and manipulating information in mind), inhibitory control (suppressing impulses and filtering out distractions), and cognitive flexibility (switching between tasks or mental frameworks). Strong EFs in childhood predict academic achievement, social competence, and long-term mental health; weaknesses in these areas that go unaddressed can persist into adulthood, undermining school performance, career prospects, and well-being.
The Background:
Interest in training these skills has grown rapidly, but most research has been conducted in Western settings. China presents a distinctive context. Collectivist values make group-based programs culturally natural, and parental investment in academic outcomes is high. Both of these factors should, in theory, work in an intervention’s favor. At the same time, tightly scheduled school days (sessions typically capped at 30 minutes or less) constrain what is actually deliverable. A growing number of randomized controlled trials (RCTs) have tested EF interventions with Chinese children, but until now, no one has pulled that evidence together systematically.
The Study:
A new network meta-analysis did exactly that. The researchers screened RCTs involving Chinese children aged 3–12, including both typically developing children and those showing subclinical signs of ADHD or autism spectrum disorder (ASD), for instance, siblings of children with an ASD diagnosis. Children who already carried a formal neurodevelopmental diagnosis were excluded. Fifty-two trials covering nearly 3,000 children met the inclusion criteria. Interventions fell into four categories:
The headline finding is that three of the four intervention types produced statistically significant improvements across all three EF domains. The exception was the hybrid physical-cognitive program, which did not reach significance for inhibitory control. Positive results across the board might sound encouraging until you look at the actual effect sizes.
The Results:
The actual effects were negligible. Every significant result fell well below what methodologists define as a “small” effect (a standardized mean difference, or SMD, of 0.2). The largest effect size in the entire analysis was an SMD of 0.097 (less than half that threshold). The authors summarize the interventions’ effects as “modest,” but that is generous phrasing for numbers that, in practical terms, amount to very little. The analysis also showed signs of publication bias, meaning that studies with null or negative results may not have been published, potentially inflating even these modest figures.
The Take-Away:
It is important to note that these results don’t necessarily mean that this is the last word on EF training. The results apply specifically to Chinese children working within the time constraints of Chinese school schedules, and they exclude children with diagnosed ADHD, a population for whom cognitive interventions sometimes show larger effects. Generalizing beyond those boundaries is unwarranted.
What the findings do suggest is that structured EF programs, as currently implemented in Chinese educational settings, are not delivering meaningful real-world benefits. Statistical significance, it is worth remembering, is not the same as practical significance, and the gap between the two is sharp here.
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