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February 21, 2024
Noting that “little is known about whether school-level stimulant therapy for ADHD is associated with NUPS [nonmedical use of prescription stimulants] among US secondary school students,” a team of American researchers searched for answers in a nationally representative sample of 3,284 U.S. secondary schools with well over 150,000 high school students.
“Previous studies,” the authors continued, “have largely neglected school-level factors associated with NUPS among US secondary school students, including school size, school geographical location, school-level racial composition, school-level rates of substance use (eg, binge drinking), and school-level stimulant therapy for ADHD.”
In surveys, students were asked if they had ever taken stimulant medications for ADHD under a physician’s or health professional’s supervision, with three possible answers: no, yes but only in the past, and yes, currently. Responses for use in the past, and separately for current use, were combined and aggregated to the school level to reflect the percentage of the study body who used prescription stimulants for ADHD.
The surveys explored NUPS by asking, “On how many occasions (if any) have you taken amphetamines or other prescription stimulant drugs on your own—that is, without a doctor telling you to take them... in your lifetime?...during the last 12 months?...during the last 30 days?”
The study team controlled for sex, race and ethnicity, parental education, GPA, binge drinking, cigarette smoking, cannabis use, cohort year, school type, grade level, urbanicity, school size, US Census region, % of student body with low grades, % female, % with at least one parent with a college degree, % White, % binge drinking during past 2 weeks, % cigarette smoking in past 30 days, and % cannabis use during the past 30 days. The analysis also included individual-level medical use of stimulant therapy for ADHD history to estimate individual-level past-year NUPS. Finally, it included both individual-level and school-level risk factors to assess individual-level past-year NUPS.
With all these adjustments, at the individual level, both high school students presently on prescribed stimulant therapy for ADHD and those who had previously been on such prescribed therapy were more than twice as likely to engage in past-year NUPS as those who were never on prescribed stimulant medication.
Turning to the school level, in schools where 12% or more of students were on prescribed stimulant therapy for ADHD, students in general were 36% more likely to engage in past-year NUPS than in schools where none of the students were on prescribed stimulant therapy for ADHD.
This is not surprising, as it confirms that students who use prescription drugs for nonmedical often get their supply from fellow students who are prescribed those drugs.
While at the individual level, binge drinking, cigarette smoking, and cannabis use were strong predictors of NUPS, at the whole-school level they had no significant effect. A poor grade point average mildly increased risk in the individual, but high percentages of students with low grades had no effect on peer NUPS. Race and ethnicity made a difference at the individual level (NUPS significantly more likely among White students than Blacks and Hispanics), but made no difference at the school level.
The team concluded, “These findings suggest that school-level stimulant therapy for ADHD and other school-level risk factors were significantly associated with NUPS and should be accounted for in risk-reduction strategies and prevention efforts.”
Sean Esteban McCabe, John E. Schulenberg, Timothy E. Wilens, Ty S. Schepis, Vita V. McCabe, and Philip T. Veliz, “Prescription Stimulant Medical and Nonmedical Use AmongUS Secondary School Students, 2005 to 2020,” JAMA Network Open (2023), https://doi.org/10.1001/jamanetworkopen.2023.8707.
The Background:
Myopia is a growing global health concern linked to conditions like macular degeneration, glaucoma, and retinal detachment. Its prevalence has surged in recent decades; by 2050, an estimated 5 billion people will have myopia. The increase is especially marked in Asia – a survey in Taiwan reports that 84% of students aged 15 to 18 are myopic, with 24% severely affected.
Dopamine is an important neurotransmitter in the retina, involved in eye development, visual signaling, and refractive changes. The dopamine hypothesis, suggesting that retinal dopamine release helps prevent myopia, has emerged as a leading theory of myopia control.
Most studies show ADHD is highly heritable, often involving dopamine system genes. ADHD is strongly associated with dopaminergic abnormalities, especially in dopamine transporter function and release dynamics.
Medications for ADHD, like methylphenidate, atomoxetine, and clonidine, help regulate dopamine to reduce symptoms.
The Study:
Given dopamine’s critical involvement in both ADHD and myopia, a Taiwanese research team hypothesized that medications for ADHD that influence dopaminergic pathways may have a significant effect on myopia risk.
To evaluate this hypothesis, the team conducted a nationwide cohort study using data from Taiwan’s National Health Insurance (NHI) program, which covers 99% of the nation’s 23 million residents and provides access to comprehensive eye care and screenings. Taiwan requires visual acuity screenings beginning at age four, with annual examinations for school-aged children to promote the early detection of visual anomalies such as myopia.
Furthermore, ADHD medication and diagnosis are tracked through compulsory diagnostic codes. This permits an accurate assessment of the effects of dopaminergic medications on myopia risk.
Propensity score allocation using a multivariable logistic regression model was applied to reduce bias from confounding influences, pairing cohorts based on similar scores.
The Results:
Comparing 133,945 individuals with ADHD with an equal number without ADHD, untreated ADHD was associated with a 22% greater risk of myopia.
However, after adjusting for covariates (gender, age, insured premium, comorbidities, location, and urbanization level), the ADHD cohort receiving medication treatment showed a 39% decreased risk of myopia relative to the untreated ADHD cohort.
Narrowing this further to the ADHD cohort receiving dopaminergic medications reduced the risk of myopia by more than half (52%) relative to the untreated ADHD cohort.
Treatment with two dopaminergic medications reduced the risk by well over two-thirds (72%) relative to the untreated ADHD cohort.
There were no significant differences between methylphenidate, atomoxetine, and clonidine. Each reduced risk by about 50%.
The team did not directly compare the ADHD cohort receiving dopaminergic medications with the non-ADHD cohort. But if there were 122 cases of myopia in the ADHD cohort for every 100 cases in the non-ADHD cohort, and dopaminergic medications halved the cases in the ADHD cohort to about 60, that would represent a roughly 40% reduction in myopia risk relative to the non-ADHD cohort.
The team concluded, “our research indicates that pharmacologically treated ADHD children have a reduced risk of myopia. Conversely, untreated ADHD children are at a heightened risk relative to those without ADHD. Moreover, the cumulative effects of ADHD medications were found to notably decrease myopia incidence, emphasizing the protective influence of dopaminergic modulation in these interventions.”
The Take-Away:
Children with untreated ADHD are more likely to develop myopia, but those receiving dopaminergic medications had a substantially lower risk. The findings suggest that ADHD medications may help protect against myopia by boosting dopamine signaling. More research is needed before firmly drawing this conclusion, but this research could open the door to new approaches for preventing myopia in at-risk children.
Background:
ADHD treatment includes medication, behavioral therapy, dietary changes, and special education. Stimulants are usually the first choice but may cause side effects like appetite loss and stomach discomfort, leading some to stop using them. Cognitive behavioral therapy (CBT) is effective but not always sufficient on its own. Research is increasingly exploring non-drug options, such as transcranial direct current stimulation (tDCS), which may boost medication effectiveness and improve results.
What is tDCS?
tDCS delivers a weak electric current (1.0–2.0 mA) via scalp electrodes to modulate brain activity, with current flowing from anode to cathode. Anodal stimulation increases neuronal activity, while cathodal stimulation generally inhibits it, though effects vary by region and neural circuitry. The impact of tDCS depends on factors such as current intensity, duration, and electrode shape. It targets cortical areas, often stimulating the dorsolateral prefrontal cortex for ADHD due to its role in cognitive control. Stimulation of the inferior frontal gyrus has also been shown to improve response inhibition, making it another target for ADHD therapy.
There is an ongoing debate about how effective tDCS is for individuals with ADHD. One study found that applying tDCS to the left dorsolateral prefrontal cortex can help reduce impulsivity symptoms in ADHD, whereas another study reported that several sessions of anodic tDCS did not lead to improvements in ADHD symptoms or cognitive abilities.
New Research:
Two recent meta-analyses have searched for a resolution to these conflicting findings. Both included only randomized controlled trials (RCTs) using either sham stimulation or a waitlist for controls.
Each team included seven studies in their respective meta-analyses, three of which appeared in both.
Both Wang et al. (three RCTs totaling 97 participants) and Wen et al. (three RCTs combining 121 participants) reported very large effect size reductions in inattention symptoms from tDCS versus controls. There was only one RCT overlap between them. Wang et al. had moderate to high variation (heterogeneity) in individual study outcomes, whereas Wen et al. had virtually none. There was no indication of publication bias.
Whereas Wen et al.’s same three RCTs found no significant reduction in hyperactivity/impulsivity symptoms, Wang et al. combined five RCTs with 221 total participants and reported a medium effect size reduction in impulsivity symptoms. This time, there was an overlap of two RCTs between the studies. Wen et al. had no heterogeneity, while Wang et al. had moderate heterogeneity. Neither showed signs of publication bias.
Turning to performance-based tasks, Wang et al. reported a medium effect size improvement in attentional performance from tDCS over controls (three RCTs totaling 136 participants), but no improvement in inhibitory control (five RCTs combining 234 persons).
Wang et al. found no significant difference in adverse events (four RCTs combining 161 participants) between tDCS and controls, with no heterogeneity. Wen et al. found no significant difference in dropout rates (4 RCTs totaling 143 individuals), again with no heterogeneity.
Wang et al. concluded, “tDCS may improve impulsive symptoms and inattentive symptoms among ADHD patients without increasing adverse effects, which is critical for clinical practice, especially when considering noninvasive brain stimulation, where patient safety is a key concern.”
Wen et al. further concluded, “Our study supported the use of tDCS for improving the self-reported symptoms of inattention and objective attentional performance in adults diagnosed with ADHD. However, the limited number of available trials hindered a robust investigation into the parameters required for establishing a standard protocol, such as the optimal location of electrode placement and treatment frequency in this setting. Further large-scale double-blind sham-controlled clinical trials that include assessments of self-reported symptoms and performance-based tasks both immediately after interventions and during follow-up periods, as well as comparisons of the efficacy of tDCS targeting different brain locations, are warranted to address these issues.”
The Take-Away:
Previous studies have shown mixed results on the benefits of this therapy on ADHD. These new findings suggest that tDCS may hold some real promise for adults with ADHD. While the technique didn’t meaningfully shift hyperactivity or impulsivity, it was well-tolerated and showed benefit, especially in self-reported symptoms. However, with only a handful of trials to draw from, it would be a mistake to suggest tDCS as a standard treatment protocol. Larger, well-designed studies are the next essential step to clarify where, how, and how often tDCS works best.
Background:
The development of ADHD is strongly associated with functional impairments in the prefrontal cortex, particularly the dorsolateral prefrontal cortex, which plays a key role in maintaining attention and controlling impulses. Moreover, imbalances in neurotransmitters like dopamine and norepinephrine are widely regarded as major neurobiological factors contributing to ADHD.
Executive functions are a group of higher-order cognitive skills that guide thoughts and actions toward goals. “Executive function” refers to three main components: inhibitory control, working memory, and cognitive flexibility. Inhibitory control helps curb impulsive actions to stay on track. Working memory allows temporary storage and manipulation of information for complex tasks. Cognitive flexibility enables switching attention and strategies in varied or demanding situations.
Research shows that about 89% of children with ADHD have specific executive function impairments. These difficulties in attention, self-control, and working memory often result in academic and social issues. Without timely intervention, these issues can lead to emotional disorders like depression, anxiety, and irritability, further affecting both physical health and social development.
Currently, primary treatments for executive function deficits in school-aged children with ADHD include medication and behavioral or psychological therapies, such as Cognitive Behavioral Therapy (CBT). While stimulant medications do improve executive function, not all patients are able to tolerate these medications. Behavioral interventions like neurofeedback provide customized care but show variable effectiveness and require specialized resources, making them hard to sustain. Safer, more practical, and long-lasting treatment options are urgently needed.
Exercise interventions are increasingly recognized as a safe, effective way to improve executive function in children with ADHD. However, systematic studies on school-aged children remain limited.
Moreover, there are two main scoring methods for assessing executive function: positive scoring (higher values mean better performance, such as accuracy) and reverse scoring (lower values mean better performance, such as reaction time). These different methods can affect how results are interpreted and compared across studies. This meta-analysis explored how different measurement and scoring methods might influence results, addressing important gaps in the research.
The Study:
Only randomized controlled trials (RCTs) involving school-aged children (6–13 years old) diagnosed with ADHD by DSM-IV, DSM-5, ICD-10, ICD-11, or the SNAP-IV scale were included. Studies were excluded if the experimental group received non-exercise interventions or exercise combined with other interventions.
Cognitive Flexibility
Using positive scoring, exercise interventions were associated with a narrowly non-significant small effect size improvement relative to controls (eight RCTs, 268 children). Using reverse scoring, however, they were associated with a medium effect size improvement (eleven RCTs, 452 children). Variation (heterogeneity) in individual RCT outcomes was moderate, with no sign of publication bias in both instances.
Inhibitory Control
Using positive scoring, exercise interventions were associated with a medium effect size improvement relative to controls (ten RCTs, 421 children). Using reverse scoring, there was an association with a medium effect size improvement (eight RCTs, 265 children). Heterogeneity was moderate with no sign of publication bias in either case.
Working Memory
Using positive scoring, exercise interventions were associated with a medium effect size improvement relative to controls (six RCTs, 321 children). Using reverse scoring, the exercise was associated with a medium effect size improvement (five RCTs, 143 children). Heterogeneity was low with no indication of publication bias in both instances.
Conclusion:
The team concluded, “Exercise interventions can effectively improve inhibitory control and working memory in school-aged children with ADHD, regardless of whether positive or reverse scoring methods are applied. However, the effects of exercise on cognitive flexibility appear to be limited, with significant improvements observed only under reverse scoring. Moreover, the effects of exercise interventions on inhibitory control, working memory, and cognitive flexibility vary across different measurement paradigms and scoring methods, indicating the importance of considering these methodological differences when interpreting results.”
Although this work is intriguing, it does not show that exercise significantly improves the symptoms of ADHD in children. This means that exercise, although beneficial for many reasons, should not be viewed as a replacement for evidence-based treatments for the disorder.
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