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March 15, 2024
There is increasing interest in digital interventions to treat ADHD symptoms and to overcome deficits in executive functioning that are associated with this disorder. Executive functions such as working memory and cognitive speed originate in the frontal lobes of the brain, and guide voluntary goal-directed behavior. They affect reading speed and accuracy, reading comprehension, attention, and impulse control, among other behaviors important to the ability to function in social, educational, and professional environments.
A Swedish study team based at Umeå University recently conducted a systematic search of the medical literature to explore the efficacy of computerized cognitive training (CCT) to improve executive functioning in adults with ADHD.
They included published randomized controlled trials (RCTs) involving adults 18 to 65 years old with a primary diagnosis of ADHD. The controls were participants with either a passive (wait-list) or active (modified simple training) intervention.
Nine RCTs with a combined total of 285 participants met inclusion criteria. Lumping together all cognitive outcome types, meta-analysis reported a small effect size improvement that was just barely statistically significant (p = .048, with p < .05 as the boundary).
However, when separated out by individual outcome types – executive functioning, cognitive speed, general short-term memory, or ADHD symptom severity – the meta-analyses found no improvements that reached statistical significance.
Moreover, all RCTs except one were judged as high risk of bias.
While it is possible that additional studies enlarging the pool of participants could lead to statistical significance, all effect sizes were small to begin with, which is not encouraging.
The team concluded, “Considering the small positive effect in this meta-analysis for overall cognitive outcomes, together with the lack of evidence for far transfer, practitioners and individuals with ADHD should weigh the costs (resources and time) against the benefits of training.”
A South Korean study team recently concluded the first RCT-only meta-analysis of game-based digital therapeutics (DTx).
Combining 14 RCTs with a total of 1,183 participants, they found a small effect size improvement in parent-rated attention symptoms for game-based DTx interventions over controls. Nine RCTs combining 424 participants likewise found a small effect size improvement in teacher-rated attention symptoms. Between-study variation (heterogeneity) was negligible, and there was no indication of publication bias.
Combining five RCTs with a total of 256 participants, they reported small effect size improvements in both parent and teacher-rated hyperactivity/impulsivity symptoms. But they found no improvement in hyperactivity symptoms alone, whether evaluated by parents or teachers. Heterogeneity was in all instances negligible, with no sign of publication bias.
The team then compared game-based DTx interventions with pharmaceutical treatment.
ADHD medications outperformed game-based DTx interventions for improvement of attention symptoms in both parent (four RCTs with a total of 128 participants) and teacher (three RCTs with 92 participants) ratings, with small-to-medium effect sizes. Medications likewise prevailed in improving hyperactivity/impulsivity symptoms, whether rated by parents or teachers, with small-to-medium effect sizes.
The team concluded, “This study is the first direct and indirect meta-analysis to compare the efficacy of game-based DTx between control and medication according to the assessor in an RCT. In conclusion, game-based DTx had a more significant effect than the control. Additionally, between medication treatment versus DTx, medication was more effective.”
Pia Elbe, Christian Bäcklund, Mariana Vega-Mendoza, Daniel Sörman, Hanna Malmberg Gavelin, Lars Nyberg, and Jessica K. Ljungberg, “Computerized Cognitive Interventions for Adults With ADHD: A Systematic Review and Meta-Analysis,” Neuropsychology (2023), https://doi.org/10.1037/neu0000890.
SuA Oh, Jina Choi, Doug Hyun Han, and EunYoung Kim, “Effects of game-based digital therapeutics on attention deficit hyperactivity disorder in children and adolescents as assessed by parents or teachers: a systematic review and meta-analysis,” European Child & Adolescent Psychiatry (2023), https://doi.org/10.1007/s00787-023-02174-z.
Antidepressants are the primary drug treatment for depressive disorders, which affect 15–20% of pregnant women. They are among the most widely prescribed medications worldwide, and their use has increased in recent decades. Understanding their reproductive safety is critical to support informed, evidence-based prescribing during pregnancy.
A new meta-analysis sheds important light on one of the most debated concerns: whether children born to mothers who took antidepressants during pregnancy face a higher risk of ADHD.
The Study:
Pooling 14 studies covering more than 14 million participants, the analysis found that prenatal antidepressant exposure was associated with a 35% higher rate of ADHD in offspring compared to no exposure. A separate look at SSRIs (the most widely prescribed class of antidepressants, including Prozac and Zoloft) across 11 studies and over four million pregnancies found an even higher apparent risk (44%) after correcting for publication bias. On the surface, these are striking numbers.
Both associations came with an important caveat: enormous variation between individual studies, a statistical red flag suggesting the results may not reflect a true underlying effect. More tellingly, the apparent risk evaporated entirely when researchers applied a more rigorous method — comparing siblings within the same family, where one child was exposed to antidepressants in the womb, and another was not.
This sibling-comparison design is particularly powerful because it automatically controls for factors that run in families: shared genes, household environment, parenting, and socioeconomic conditions. When those influences are held constant, the link between antidepressant exposure and ADHD disappears. The same pattern held for SSRIs specifically.
Two other antidepressant classes, SNRIs (serotonin norepinephrine reuptake inhibitors) and tricyclics, showed no significant association in any analysis.
“Confounding by Indication”:
The probable driver of the initial association is what researchers call confounding by indication. The very condition being treated (depression) is itself a risk factor for ADHD in offspring, independently of any medication. Mothers with more severe depression are also more likely to be prescribed antidepressants, meaning the drug and the underlying illness are difficult to disentangle in standard analyses. Sibling studies cut through this problem cleanly.
The Take-Away:
The authors concluded that the association between antidepressants and ADHD risk was non-significant across all analyses designed to account for these confounding factors. This doesn’t mean antidepressants are without any reproductive considerations, but it does suggest that ADHD risk, at least, is driven by heritable and family-level factors rather than medication exposure itself.
For clinicians and patients weighing the risks of treating or not treating depression during pregnancy, this distinction matters considerably.
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.
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