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February 15, 2022
Noting that "despite a lack of solid evidence for their use, rTMS [repetitive transcranial magnetic stimulation]and tDCS [transcranial direct current stimulation] are already offered clinically and commercially in ADHD," and that a recent meta-analysis of ten tDCS studies found small but significant improvements in outcomes, but had several methodological shortcomings and did not include two studies reporting mostly null effects, a team of British neurologists performed a meta-analysis of all twelve sham-controlled, non-open-label, studies found in a comprehensive search of the peer-reviewed literature.
Ten of the twelve randomized-controlled trials used anodal stimulation of the dorsolateral prefrontal cortex, while the other two used anodal stimulation of the right inferior frontal cortex.
The trials explored several measures of cognition. The research team carried out a meta-analysis of all twelve trials, with a total of 232 participants, and found no significant improvement in attention scores from CDC, relative to sham stimulation. A second meta-analysis, of eleven trials with a total of 220 participants, assessed the efficacy of tDCS on improving inhibition scores, and again found no significant effect. A third meta-analysis, encompassing eight trials with a total of 124 participants, evaluated the efficacy of tDCS on improving processing speed scores, once again finding no significant effect.
The latter two meta-analyses approached the border of significance, prompting the authors to speculate that larger sample sizes could bring the results just over the threshold of significance. Even so, effect sizes would be small.
It is also possible that the trials focused on regions of the brain suboptimal for this objective, and thus the authors "cannot rule out the possibility that stimulation of other prefrontal regions (such as the right hemispheric inferior frontal cortex or dorsolateral prefrontal cortex or parietal regions), multiple session tDCS or tDCS in combination with cognitive training could improve clinically or cognitive functions in ADHD."
As to concerns about safety, on the other hand, "stimulation was well-tolerated overall."
The authors concluded that based on current evidence, tDCS of the dorsolateral prefrontal cortex cannot yet be recommended as an alternative Neurotherapy for ADHD.
Samuel J. Westwood, Ph.D.; Joaquim Radua, Ph.D.; Katya Rubia, Ph.D., "Noninvasive brain stimulation in children and adults with attention-deficit/hyperactivity disorder: a systematic review and meta-analysis," Journalof Psychiatry & Neuroscience(2020), https://doi.org/10.1503/jpn.190179.
EBI-ADHD:
If you live with ADHD, treat ADHD, or write about ADHD, you’ve probably run into the same problem: there’s a ton of research on treatments, but it’s scattered across hundreds of papers that don’t talk to each other. The EBI-ADHD website fixes that.
EBI-ADHD (Evidence-Based Interventions for ADHD) is a free, interactive platform that pulls together the best available research on how ADHD treatments work and how safe they are. It’s built for clinicians, people with ADHD and their families, and guideline developers who need clear, comparable information rather than a pile of PDFs. EBI-ADHD Database The site is powered by 200+ meta-analyses covering 50,000+ participants and more than 30 different interventions. These include medications, psychological therapies, brain-stimulation approaches, and lifestyle or “complementary” options.
The heart of the site is an interactive dashboard. You can:
The dashboard then shows an evidence matrix: a table where each cell is a specific treatment–outcome–time-point combination. Each cell tells you two things at a glance:
Clicking a cell opens more detail: effect sizes, the underlying meta-analysis, and how the certainty rating was decided.
EBI-ADHD is not just a curated list of papers. It’s built on a formal umbrella review of ADHD interventions, published in The BMJ in 2025. That review re-analyzed 221 meta-analyses using a standardized statistical pipeline and rating system.
The platform was co-created with 100+ clinicians and 100+ people with lived ADHD experience from around 30 countries and follows the broader U-REACH framework for turning complex evidence into accessible digital tools.
Why it Matters
ADHD is one of the most studied conditions in mental health, yet decisions in everyday practice are still often driven by habit, marketing, or selective reading of the literature. EBI-ADHD offers something different: a transparent, continuously updated map of what we actually know about ADHD treatments and how sure we are about it.
In short, it’s a tool to move conversations about ADHD care from “I heard this works” to “Here’s what the best current evidence shows, and let’s decide together what matters most for you.”
The Background:
Meta-analyses have previously suggested a link between maternal thyroid dysfunction and neurodevelopmental disorders (NDDs) in children, though some studies report no significant difference. Overweight and obesity are more common in children and adolescents with NDDs. Hypothyroidism is often associated with obesity, which may result from reduced energy expenditure or disrupted hormone signaling affecting growth and appetite. These hormone-related parameters could potentially serve as biomarkers for NDDs; however, research findings on these indicators vary.
The Study:
A Chinese research group recently released a meta-analysis examining the relationship between neurodevelopmental disorders (NDDs) and hormone levels – including thyroid, growth, and appetite hormones – in children and adolescents.
The analysis included peer-reviewed studies that compared hormone levels – such as thyroid hormones (FT3, FT4, TT3, TT4, TSH, TPO-Ab, or TG-Ab), growth hormones (IGF-1 or IGFBP-3), and appetite-related hormones (leptin, ghrelin, or adiponectin) – in children and adolescents with NDDs like ADHD, against matched healthy controls. To be included, NDD cases had to be first-diagnosis and medication-free, or have stopped medication before testing. Hormone measurements needed to come from blood, urine, or cerebrospinal fluid samples, and all studies were required to provide both means and standard deviations for these measurements.
Meta-analysis of nine studies encompassing over 5,700 participants reported a medium effect size increase in free triiodothyronine (FT3) in children and adolescents with ADHD relative to healthy controls. There was no indication of publication bias, but variation between individual study outcomes (heterogeneity) was very high. Further analysis showed FT3 was only significantly elevated in the predominantly inattentive form of ADHD (three studies), again with medium effect size, but not in the hyperactive/impulsive and combined forms.
Meta-analysis of two studies combining more than 4,800 participants found a small effect size increase in thyroid peroxidase antibody (TPO-Ab) in children and adolescents with ADHD relative to healthy controls. In this case, the two studies had consistent results. Because only two studies were involved, there was no way to evaluate publication bias.
The remaining thyroid hormone meta-analyses, involving 6 to 18 studies and over 5,000 participants in each instance, found no significant differences in levels between children and adolescents with ADHD and healthy controls.
Meta-analyses of six studies with 317 participants and two studies with 192 participants found no significant differences in growth hormone levels between children and adolescents with ADHD and healthy controls.
Finally, meta-analyses of nine studies with 333 participants, five studies with 311 participants, and three studies with 143 participants found no significant differences in appetite-related hormone levels between children and adolescents with ADHD and healthy controls.
The Conclusion:
The team concluded that FT3 and TPO-Ab might be useful biomarkers for predicting ADHD in youth. However, since FT3 was only linked to inattentive ADHD, and TPO-Ab’s evidence came from just two studies with small effects, this conclusion may overstate the meta-analysis results.
Our Take-Away:
Overall, this meta-analysis found only limited evidence that hormone differences are linked to ADHD. One thyroid hormone (FT3) was higher in children with ADHD—mainly in the inattentive presentation—but the findings varied widely across studies. Another marker, TPO-Ab, showed a small increase, but this came from only two studies, making the result less certain. For all other thyroid, growth, and appetite-related hormones, the researchers found no meaningful differences between children with ADHD and those without. While FT3 and TPO-Ab may be worth exploring in future research, the current evidence is not strong enough to consider them reliable biomarkers.
Background:
Recent progress in reproductive medicine has increased the number of children conceived via assisted reproductive techniques (ART). These include:
Although ART helps with infertility, there are concerns about its long-term effects on offspring, especially regarding neurodevelopment. Factors such as hormonal treatments, gamete manipulation, altered embryonic environments, as well as parental age and infertility, may influence brain development and raise the risk of neurodevelopmental and mental health disorders.
With previous studies finding conflicting results on a possible association between ART and increased risk of mental health disorders, an Indian research team has just published a new meta-analysis exploring this topic.
The Study:
Studies were eligible if they were observational (cohort, case-control, or cross-sectional), reported confounder-adjusted effect sizes for ADHD, and were published in English in peer-reviewed journals.
A meta-analysis of eight studies encompassing nearly twelve million individuals indicated a 7% higher prevalence of ADHD in offspring conceived via IVF/ICSI compared to those conceived naturally. The heterogeneity among studies was minimal, and no evidence of publication bias was observed.
The study’s 95% confidence interval ranged from 4% to 10%. Further analysis of five studies comprising almost nine million participants that distinguished outcomes by sex revealed that the increase in ADHD risk among female offspring was not statistically significant. In contrast, the elevated risk in male offspring persisted, though it was marginally significant, with the lower bound of the confidence limit at only 1%.
Results:
A meta-analysis of three studies (1.4 million participants) found a 13% higher rate of ADHD in children conceived via ovulation induction/intrauterine insemination (OI/IUI) compared to natural conception. The effect size, though doubled, remains small. Minimal heterogeneity and no publication bias were observed.
The team concluded, “The review found a small but statistically significant moderate certainty evidence of an increased risk of ADHD in those conceived through ART, compared to spontaneous conception. The magnitude of observed risk is small and is reassuring for parents and clinicians.”
Our Take-Away:
Overall, the meta-analysis points to a small, but measurable increase in ADHD diagnoses among children conceived through ART, but the effect sizes are modest and supported by moderate-certainty evidence. And we must always keep in mind that the researchers who wrote the original articles could not correct for all possible confounds. These findings suggest that while reproductive technologies may introduce slight variation in neurodevelopmental outcomes, the effects are small and uncertain. For families and clinicians, the results are generally reassuring: ART remains a safe and effective avenue to parenthood, and the results of this study should not be viewed as a prohibitive concern. Thoughtful developmental monitoring and open, evidence-based counseling can help ensure that ART-conceived children receive support that caters to their individual needs.
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