Meta-analysis Reports No Significant Evidence for Efficacy of Neuromechanistic Treatments for Adult ADHD

ADHD is hypothesized to arise from 1) poor inhibitory control resulting from impaired executive functions which are associated with reduced activation in the dorsolateral prefrontal cortex and increased activation of some subcortical regions; and 2)hyperarousal to environmental stimuli, hampering the ability of the executive functioning system, particularly the medial frontal cortex, orbital and ventromedial prefrontal areas, and subcortical regions such as the caudate nucleus, amygdala, nucleus accumbens, and thalamus, to control the respective stimuli.

These brain anomalies, rendered visible through magnetic resonance imaging, have led researchers to try new means of treatment to directly address the deficits. Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique that uses a weak electrical current to stimulate specific regions of the brain.

Efficacy:

A team of researchers from Europe and ran performed a systematic search of the literature and identified fourteen studies exploring the safety and efficacy of tDCS. Three of these studies examined the effects on ADHD symptoms. They found a large effect size for the inattention subscale and a medium effect size for the hyperactivity/impulsivity. Yet, as the authors cautioned, "a definite conclusion concerning the clinical efficacy of tDCS based on the results of these three studies is not possible."

The remaining studies investigated the effects on specific neuropsychological and cognitive deficits in ADHD:

•  Working memory was improved by anodal stimulation - but not cathodal stimulation - of the left dorsolateral prefrontal cortex. Anodal stimulation of the right inferior frontal gyrus had no effect.
•  Response inhibition: Anodal stimulation of the left or right dorsolateral prefrontal cortex was more effective than anodal stimulation of the bilateral prefrontal cortex.
• Motivational and emotional processing was improved only with stimulation of both the dorsolateral prefrontal cortex and orbitofrontal cortex.

The fact that heterogeneity in the methodology of these studies made meta-analysis impossible means these results, while promising, cannot be seen as in any way definitive.

Safety:

Ten studies examined childhood ADHD. Three found no adverse effects either during or after tDCS. One study reported a feeling of "shock" in a few patients during tDCS. Several more reported skin tingling and itching during tDCS. Several also reported mild headaches.

The four studies of adults with ADHD reported no major adverse events. One study reported a single incident of acute mood change, sadness, diminished motivation, and tension five hours after stimulation. Another reported mild instances of skin tingling and burning sensations.

To address side effects such as tingling and itching, the authors suggested reducing the intensity of the electrical current and increasing the duration. They also suggested placing electrodes at least 6 cm apart to reduce current shunting through the ski. For children, they recommended the use of smaller electrodes for better focus in smaller brains.

The authors concluded, "The findings of this systematic review suggest at least a partial improvement of symptoms and cognitive deficits in ADHD by tDCS. They further suggest that stimulation parameters such as polarity and site are relevant to the efficacy of tDCS in ADHD. Compared to cathodal stimulation, Anodal tDCS seems to have a superior effect on both the clinical symptoms and cognitive deficits. However, the routine clinical application of this method as an efficient therapeutic intervention cannot yet be recommended based on these studies ..."

The U.S. government released a sweeping document titled The MAHA Report: Making Our Children Healthy Again, developed by the President’s “Make America Healthy Again” Commission. Chaired by public figures and physicians with ties to the current administration, the report presents a broad diagnosis of what it calls a national health crisis among children. It cites rising rates of obesity, diabetes, allergies, mental illness, neurodevelopmental disorders, and chronic disease as signs of a generation at risk.

The report's overarching goal is to shift U.S. health policy away from reactive, pharmaceutical-based care and toward prevention, resilience, and long-term well-being. It emphasizes reforming the food system, reducing environmental chemical exposure, addressing lifestyle factors like physical inactivity and screen overuse, and rethinking what it calls the “overmedicalization” of American children.

While some of the report’s arguments are steeped in political rhetoric and controversial claims—particularly around vaccines and mental health diagnoses—others are rooted in well-established public health science. This blog aims to highlight where the MAHA Report gets the science right, especially as it relates to childhood health and ADHD.

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Some of the Good Ideas in the MAHA Report:

Although the MAHA Report contains several debatable assertions, it also outlines six key public health priorities that are well-supported by decades of research. If implemented thoughtfully, these recommendations might make a meaningful difference in the health of American children:

Reduce Ultra-Processed Food (UPF) Consumption

UPFs now make up nearly 70% of children’s daily calories. These foods are high in added sugars, refined starches, unhealthy fats, and chemical additives, but low in nutrients. Studies—including a 2019 NIH-controlled feeding study—show that UPFs promote weight gain, overeating, and metabolic dysfunction.  What can help: Tax incentives for fresh food retailers, improved school meals, front-of-pack labeling, and food industry regulation.

Promote Physical Activity and Limiting Sedentary Time

Most American children don’t get the recommended 60 minutes of physical activity per day. This contributes to obesity, cardiovascular risk, and even mental health issues. Physical activity is known to improve attention, mood, sleep, and self-regulation.   What can help: Mandatory daily PE, school recess policies, walkable community infrastructure, and screen-time education.

Addressing Sleep Deprivation

Teens today sleep less than they did a decade ago, in part due to screen use and early school start times. Sleep loss is linked to depression, suicide risk, poor academic performance, and metabolic problems.  What can help: Later school start times, family education about sleep hygiene, and limits on evening screen exposure.

Improving Maternal and Early Childhood Nutrition

The report indirectly supports actions that are backed by strong evidence: encouraging breastfeeding, supporting maternal whole-food diets, and improving infant nutrition. These are known to reduce chronic disease risk later in life.

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What MAHA Says About ADHD:

ADHD is one of the most discussed neurodevelopmental disorders in the MAHA Report, but many of its claims about ADHD are misleading, oversimplified, or inconsistent with decades of scientific evidence, much of which is described in the International Consensus Statement on ADHD, and other references given below.

✔️ Accurate: ADHD diagnoses are increasing.

This is true. Diagnosis rates have risen over the past two decades, due in part to better recognition, broadened diagnostic criteria, and changes in healthcare access.  Diagnosis rates in some parts of the country are too high, but we don’t know why.  That should be addressed and investigated.  MAHA attributes increasing diagnoses to ‘overmedicalization’.   That is a hypothesis worth testing but not a conclusion we can draw from available data.

❌ Misleading: ADHD is caused by processed food, screen time, or chemical exposures.

These have been associated with ADHD but have not been documented as causes. ADHD is highly heritable, with genetic factors accounting for 70–80% of the risk.   Unlike genetic studies, environmental risk studies are compromised by confounding variables.   There are good reasons to address these issues but doing so is unlikely to reduce diagnostic rates of ADHD. 

❌ Inaccurate: ADHD medications don’t work long-term.

The report criticizes stimulant use but fails to note that ADHD medications are among the most effective psychiatric treatments, especially when consistently used.  They cite the MTA study’s long term outcome study of kids assigned to medication vs. placebo as showing medications don’t work in the long term.  But that comparison is flawed because during the follow-up period, many kids on medication stopped taking them and many on placebo started taking medications.   Many studies document that medications for ADHD protect against many real-world outcomes such as accidental injuries, substance abuse and even premature death.

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How the MAHA Report Could Still Help People with ADHD:

Despite the issues discussed above, the MAHA Report can indirectly help children and adults with ADHD by pushing for systemic changes that reduce ultra-processed food consumption, increase physical activity, and motivate better sleep practices.

In other words, you don’t need to reject the diagnosis of ADHD to support broader changes in how we feed, educate, and care for children. A more supportive, less toxic environment benefits everyone—including those with ADHD.

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ADHD is associated with impaired executive functioning. Executive functions are a set of mental skills that include working memory, flexible thinking, and self-control. These are skills we use every day to learn, work, and manage daily life. Trouble with executive function can make it hard to focus, follow directions, and handle emotions. 

A Chinese study team searched for studies on non-pharmacological treatments of children and adolescents with ADHD aged 5 to 18 years intended to improve their executive functioning. 

An initial methodological weakness was the decision to combine studies using formal ADHD diagnoses based on professional psychiatric manuals (DSM 3/4/5 and ICD 10/11) and studies relying on other methods such as parent reports.

This lack of rigor in identifying ADHD is surprising given that the team used studies that directly measured executive functioning through neurocognitive tasks, excluding those that relied on parent- or teacher-reported questionnaires. 

67 studies involving 74 training interventions met the criteria. Meta-analysis of all these studies, encompassing a total of 3,101 participants, suggested medium-to-large effect size improvements in executive functioning. There was evidence of publication bias, but trim-and-fill adjustment increased the estimated effect size to large.

Nevertheless, there were further methodological shortcomings:

• The meta-analysis mixed studies of substantially different interventions: cognitive training, executive function-specific curriculum, game-based training, neurofeedback, mindfulness, and physical exercise.
• There was tremendous variation (heterogeneity) between study outcomes. Such inconsistency casts doubt on the outcome unless subgroup analysis can explain it. 

In this case, subgroup analysis mostly failed to explain the heterogeneity, with a single exception. Meta-analysis of the 16 studies with 744 participants that explored executive function-specific curriculum found small-to-medium effect size improvements, with no heterogeneity. 

Unfortunately, the team did not perform a separate publication bias analysis on this subgroup, just as it failed to do so on any of the other subgroups.

By far the strongest evidence of benefit came from meta-analysis of the 17 studies with 558 participants evaluating physical exercise. Here the outcome pointed to very large effect size improvements in executive functioning. Yet once again, heterogeneity was extremely high. Breaking this down further between aerobic exercise and cognitively engaged physical exercise made no difference. Both types had the same very high effect size, with very wide heterogeneity. Again, there was no separate evaluation of publication bias on this group.

Meta-analyses of thirteen studies of neurofeedback combining 444 participants, and fifteen studies of cognitive training encompassing 727 participants, both pointed to just-short-of-large effect size improvements in executive function. Meta-analysis of twelve studies of game-based training with 598 participants indicated medium effect size gains. But again, in all three subgroups there was great variation between studies, and no analysis of publication bias.

While these meta-analyses are suggestive of efficacy, especially for physical exercise interventions, their methodological shortcomings mean we will have to await more rigorous meta-analyses to draw any more settled conclusions. Moreover, these meta-analyses did not evaluate the adequacy of the control groups used in the trials, which is a big shortcoming given prior work showing that the effect of non-pharmacologic treatments are very weak or non-existent when adequate controls are used.