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Computerized cognitive training (CCT) uses computers to try to strengthen cognitive skills and processes, reduce ADHD symptoms, and improve executive functioning. Executive functions are cognitive processes and mental skills that help individuals plan, monitor, and successfully execute their goals.
CCT programs target one or more cognitive processes such as motor inhibition, interference inhibition, sustained attention, and working memory. They ramp up task difficulty as performance improves. The goal is to harness the brain’s inherent adaptability (neuroplasticity) to boost performance.
A European study team that previously probed the efficacy of CCT through meta-analysis had been unable to provide a robust estimate of effect size due to an insufficient number of high-quality trials with probably blinded outcomes. Noting that “there have been a considerable number of new RCTs [randomized controlled trials] published, many with larger samples, well-controlled designs and blinded outcomes,” the team performed an updated systematic review and meta-analysis.
They included RCTs with participants of any age who either had a clinical diagnosis of ADHD or were above cut-off on validated ADHD rating scales. RCTs had to have been peer-reviewed and published in an academic journal, and to have reported a validated outcome measure of ADHD symptoms, neuropsychological processes, and/or academic outcomes.
Fourteen RCTs with a combined total of 631 participants had probably blinded outcomes. Meta-analysis of these studies yielded no significant effect on either overall ADHD symptoms or hyperactivity/impulsivity symptoms. There was a marginally significant reduction in inattention symptoms, but the effect size was small. Between-study variation (heterogeneity) was negligible and there was no sign of publication bias.
Regarding academic outcomes, meta-analyses revealed no gain in arithmetic ability or reading fluency. There was a small but not statistically significant improvement in reading comprehension. Heterogeneity was minimal, with no indication of publication bias.
With two related exceptions, meta-analyses of RCTs measuring executive functions likewise reported no significant improvements in attention, interference inhibition (initial stage in controlling impulsive behavior), motor inhibition (follow-up stage in controlling impulsive behavior), non-verbal reasoning, processing speed, and set shifting (the ability to unconsciously shift attention between one task and another).
The exceptions were for working memory tasks. Meta-analysis of 15 RCTs with a combined 753 participants reported a highly significant small-to-medium effect size improvement in verbal working memory. A separate meta-analysis of nine RCTs with a total of 441 participants similarly reported a highly significant improvement in visuospatial working memory, this time with medium effect size.
The team concluded, “There was no empirical support for the use of CCT as a stand-alone intervention for ADHD symptoms based on the largest and most comprehensive meta-analysis of RCTs conducted to date. Small effects, of likely limited clinical importance, on inattention symptoms were found – but these were limited to the setting in which the intervention was delivered. Robust evidence of small- to-moderate improvements in visual-spatial and verbal STM/WM tasks did not transfer to other domains of executive functions or academic outcomes.”
Samuel J. Westwood, Valeria Parlatini, Katya Rubia, Samuele Cortese, Edmund J. S. Sonuga-Barke, and European ADHD Guidelines Group (EAGG), “Computerized cognitive training in attention-deficit/hyperactivity disorder (ADHD): a meta-analysis of randomized controlled trials with blinded and objective outcomes,” Molecular Psychiatry (2023), https://doi.org/10.1038/s41380-023-02000-7.
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.
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.
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