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June 19, 2025
Background:
In Iceland, treatment with ADHD medication can only be initiated by psychiatrists or pediatricians with experience in diagnosing neurodevelopmental disorders. The diagnostic evaluation is most often carried out by a psychologist or psychiatrist, and must be confirmed by a psychiatrist.
Some previous studies have suggested a small but significant increased risk of psychosis or mania associated with ADHD medication, while others have not.
Iceland has a single-payer national healthcare insurance system that tracks virtually its entire population. An Icelandic research team accessed two administrative databases with nationwide coverage – the Icelandic Prescription Medicines Register and the Icelandic Hospital Discharge Register – to explore this relationship among all adults from 2010 through 2022.
They included three categories of ADHD medications prescribed in Iceland: amphetamines, including dexamphetamine and lisdexamphetamine; methylphenidate; and atomoxetine. In Iceland, methylphenidate or atomoxetine must be prescribed and tried first before switching to lisdexamphetamine or dexamphetamine.
Method:
Diagnoses of mania or psychosis recorded in electronic health records were used to identify individuals who were admitted to a psychiatric ward within one year of starting treatment with a specific class of ADHD medication. First-onset psychosis or mania was defined as the emergence of these conditions in individuals with no prior history, diagnosis, or hospitalization for psychosis or mania.
A total of 16,125 adults began using an ADHD medication for the first time during the 13-year study period.
Methylphenidate was the most used ADHD medication among those admitted for psychosis or mania (25 out of 61; 41%), reflecting its status as the most frequently prescribed stimulant during the study period. It was followed by amphetamines (21 out of 61; 34.4%) and atomoxetine (15 out of 61; 24.6%).
Half of those hospitalized had previously received a diagnosis of substance use disorder. One in nine (11%) of those hospitalized acknowledged misuse of the type of ADHD medication they had been prescribed.
Within a year of discharge, 42 out of the 61 patients (68.9%) had been prescribed an ADHD medication again. Among those, one in four (11 out of 42; 26%) were readmitted for psychosis or mania within the following year.
The team noted, “It is concerning that most patients (68.9%) in our study resumed ADHD drug treatment within a year of hospital discharge … However, some studies have reported that the use of psychostimulants or atomoxetine to treat ADHD in individuals with psychotic disorders did not increase the risk of hospitalisation for psychosis if used concurrently with antipsychotic medication or that such use might even reduce this risk.”
Findings:
By comparison with the general population, adults initiating ADHD medications had eight times the relative risk of being admitted for psychosis or mania within the first year.
The absolute risk was low: 0.38% overall for those initiating ADHD medication. Adjusting for the general population risk of hospitalization for first-onset psychosis or mania, more than 300 patients would need to be initiated to ADHD medication to generate one hospital admission for psychosis or mania.
The team conceded, “Confounders of real-life clinical settings, such as non-disclosed ADHD drug abuse or misuse or some degree of substance abuse, may have influenced our findings.”
A further, unmentioned, limitation is that the team did not perform any of the usual adjustments for confounding variables, critically including co-occurring (comorbid) psychiatric disorders known to be common with ADHD, and likely to have a major effect on the relative risk of hospitalization.
Given the very small increase in risk along with the methodological flaws, the team’s suggestion of a “potential causal role of ADHD drugs in the development of first-onset psychosis or mania” is unsubstantiated and speculative. This is especially so given other studies suggesting no increased risk for psychosis due to these medications.
In any event, causation cannot be established through observational studies.
Ragna Kristin Gudbrandsdottir, Engilbert Sigurdsson, Þorsteinn Ivar Albertsson, Halldora Jonsdottir, and Oddur Ingimarsson, “Risk of hospitalisation for first-onset psychosis or mania within a year of ADHD medication initiation in adults with ADHD,” BMJ Mental Health (2025), 28: 1–7, https://doi.org/10.1136/bmjment-2024-301521.
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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