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November 16, 2023
The US Center for Disease Control's (CDC)review of ADHD starts with the statement: "Attention-deficit/hyperactivity disorder (ADHD) is a serious public health problem affecting many children and adults" (http://www.cdc.gov/ncbddd/adhd/research.html). My colleagues and I recently reviewed the ADHD literature. That let us describe ADHD as "... a seriously impairing, often persistent neurobiological disorder of high prevalence..." (Faraone et al., 2015). The figure 1, which comes from that paper, provides an overview of the lifetime trajectory of ADHD-associated morbidity.
Especially compelling data about ADHD and injuries comes from a recent paper, in Lancet Psychiatry, which used the Danish national registers to follow a cohort of 710,120 children (Dalsgaard et al., 2015a). Compared with children not having ADHD, those with ADHD were 30% more likely to sustain injuries than other children. Pharmacotherapy for ADHD reduced the risk for injuries by 32% from 5 to 10 years of age. Pharmacotherapy for ADHD reduced emergency room visits by 28.2% at age 10and 45.7% at age 12.
These results are shown in Figure 2, taken from the publication.
Especially compelling data about ADHD and injuries comes from a recent paper, in Lancet Psychiatry, which used the Danish national registers to follow a cohort of 710,120 children (Dalsgaard et al., 2015a). Compared with children not having ADHD, those with ADHD were 30% more likely to sustain injuries than other children. Pharmacotherapy for ADHD reduced the risk for injuries by 32% from 5 to 10 years of age. Pharmacotherapy for ADHD reduced emergency room visits by 28.2%at age 10and 45.7% at age 12.
These results are shown in Figure2, taken from the publication. The Figure compares the prevalence of injuries among three groups. ADHD children treated with medication, ADHD children not treated with medication, and children without ADHD. The Figure shows how ADHD risk for injuries occurs for all age groups. It also shows how the risk for injuries drops with treatment so that by age 12, the prevalence of injuries among treated ADHD children is the same as the prevalence of injuries for children without ADHD.
Documented examples of ADHD-associated injuries which impact day-to-day functioning include severe burns (Fritz and Butz, 2007), dental injuries (Sabuncuoglu, 2007), penetrating eye injuries (Bayar et al., 2015), the hospital treated injuries (Hurtig et al., 2013), and head injuries (DiScala et al., 1998). In one study (DiScala et al., 1998), when compared to other children admitted to the hospital for injuries, ADHD children were more likely to sustain injuries in multiple body regions (57.1% vs 43%), sustain head injuries (53% vs 41%), and to be severely injured as measured by the Injury Severity Score (12.5% vs5.4%) and the Glasgow Coma Scale (7.5% vs 3.4%).
Injuries are a substantial cause of ADHD-associated premature death. This assertion comes from the work of Dalsgaard et al. (2015b)based on the same Danish registry discussed above. In this second study, ADHD was associated with an increased risk for premature death and 53% of those deaths were due to injuries. They reported the risk for premature death in three age groups: 1-5, 6-17, and >17. For all three age groups, they found a greater risk for death in the ADHD group. For ages 6 to 17 and greater than 17. The ADHD-associated risk for mortality remained significant after excluding individuals with antisocial or substance use disorders.
There are currently no data about the effect of ADHD treatment on ADHD-associated premature death. We do, however, know from the data reviewed above that ADHD treatment reduces injuries and that half the deaths in the ADHD group were due to injuries. From this, we infer that ADHD treatments could reduce the risk of ADHD-associated premature death.
Two other ADHD-associated mobilities, obesity and cigarette smoking, have clear medical consequences. In a meta-analysis of 42 cross-sectional studies comprising 48,161 people with ADHD and 679,975 controls, my colleagues and I reported that the pooled prevalence of obesity was increased by about 40% in ADHD children compared with non-ADHD children and by about 70% in ADHD adults compared with non-ADHD adults(Cortese et al.,2015). The association between ADHD and obesity was significant for ADHD medication-naïve subjects but not for those medicated for ADHD, which suggests that medication reduces the risk for obesity.
Likewise, a meta-analysis of 27 longitudinal studies assessed the risk for several addictive disorders with sample sizes ranging from 4142 to 4175 for ADHD and 6835 to 6880 for non-ADHD controls (Lee et al., 2011). Children with ADHD were at higher risk for disorders of abuse or dependence on nicotine, alcohol, marijuana, cocaine, and other unspecified substances. Another meta-analysis (42 studies totaling, 2360 participants) showed that medications for ADHD reduced the ADHD-associated risk for smoking (Schoenfelder et al., 2014). The authors concluded that, for ADHD patients, "Consistent stimulant treatment for ADHD may reduce the risk of smoking". This finding is especially notable given that, for ADHD youth, cigarette smoking is a gateway drug to more serious addictions (Biederman et al., 2006).
Yes, ADHD is a serious disorder. Although most ADHD people will be spared the worst of these outcomes, they must be considered by parents and patients when weighing the pros and cons of treatment options.
Bayar, H., Coskun, E., Oner, V., Gokcen,C., Aksoy, U., Okumus, S. & Erbagci, I. (2015). Association between penetrating eye injuries and attention deficit hyperactivity disorder in children.Br J Ophthalmol99, 1109-11.
Biederman, J., Monuteaux, M., Mick, E., Wilens, T., Fontanella, J.,Poetzl, K. M., Kirk, T., Masse, J. & Faraone, S. V. (2006). Is cigarette smoking a gateway drug to subsequent alcohol and illicit drug use disorders? A controlled study of youths with and without ADHD. Biol Psychiatry59, 258-64.
Cortese, S., Moreira-Maia, C. R., St Fleur, D., Morcillo-Penalver, C.,Rohde, L. A. & Faraone, S. V. (2015). Association Between ADHD and Obesity: A Systematic Review and Meta-Analysis. Am J Psychiatry, appiajp201515020266.
Dalsgaard, S., Leckman, J. F., Mortensen, P. B., Nielsen, H. S. &Simonsen, M. (2015a). Effect of drugs on the risk of injuries in children with attention deficit hyperactivity disorder: a prospective cohort study. Lancet Psychiatry2, 702-9.
Dalsgaard, S., Ostergaard, S. D., Leckman, J. F., Mortensen, P. B.& Pedersen, M. G. (2015b). Mortality in children, adolescents, and adults with attention deficit hyperactivity disorder: a nationwide cohortstudy. Lancet385, 2190-6.
DiScala, C., Lescohier, I., Barthel, M. & Li, G. (1998).Injuries to children with attention deficit hyperactivity disorder. Pediatrics102, 1415-21.
Faraone, S. V., Asherson, P., Banaschewski, T., Biederman, J.,Buitelaar, J. K., Ramos-Quiroga, J. A., Rohde, L. A., Sonuga-Barke, E. J. S.,Tannock, R. & Franke, B. (2015). Attention deficit hyperactivitydisorder. In Nature Reviews: DiseasePrimers.
Fritz, K. M. & Butz, C. (2007). Attention Deficit/Hyperactivity Disorder and pediatric burn injury: important considerations regarding premorbid risk. Curr Opin Pediatr19, 565-9.
Hurtig, T., Ebeling, H., Jokelainen, J., Koivumaa-Honkanen, H. &Taanila, A. (2013). The Association Between Hospital-Treated Injuries and ADHD Symptoms in Childhood and Adolescence: A Follow-Up Study in the Northern Finland Birth Cohort 1986. J Atten Disord.
Lee, S. S., Humphreys, K. L., Flory, K., Liu, R. & Glass, K. (2011).Prospective association of childhood attention-deficit/hyperactivity disorder(ADHD) and substance use and abuse/dependence: a meta-analytic review. Clin Psychol Rev31, 328-41.
Sabuncuoglu, O. (2007). Traumatic dental injuries and attention-deficit/hyperactivity disorder: is there a link? Dent Traumatol23,137-42.
Schoenfelder, E. N., Faraone, S. V. & Kollins, S. H. (2014).Stimulant treatment of ADHD and cigarette smoking: a meta-analysis. Pediatrics133, 1070-1080.
Background:
Despite recommendations for combined pharmacological and behavioral treatment in childhood ADHD, caregivers may avoid these options due to concerns about side effects or the stigma that still surrounds stimulant medications. Alternatives like psychosocial interventions and environmental changes are limited by questionable effectiveness for many patients. Increasingly, patients and caregivers are seeking other therapies, such as neuromodulation – particularly transcranial direct current stimulation (tDCS).
tDCS seeks to enhance neurocognitive function by modulating cognitive control circuits with low-intensity scalp currents. There is also evidence that tDCS can induce neuroplasticity. However, results for ADHD symptom improvement in children and adolescents are inconsistent.
The Method:
To examine the evidence more rigorously, a Taiwanese research team conducted a systematic search focusing exclusively on randomized controlled trials (RCTs) that tested tDCS in children and adolescents diagnosed with ADHD. They included only studies that used sham-tDCS as a control condition – an essential design feature that prevents participants from knowing whether they received the active treatment, thereby controlling for placebo effects.
The Results:
Meta-analysis of five studies combining 141 participants found no improvement in ADHD symptoms for tDCS over sham-TDCS. That held true for both the right and left prefrontal cortex. There was no sign of publication bias, nor of variation (heterogeneity) in outcomes among the RCTs.
Meta-analysis of six studies totaling 171 participants likewise found no improvement in inattention symptoms, hyperactivity symptoms, or impulsivity symptoms for tDCS over sham-TDCS. Again, this held true for both the right and left prefrontal cortex, and there was no sign of either publication bias or heterogeneity.
Most of the RCTs also performed follow-ups roughly a month after treatment, on the theory that induced neuroplasticity could lead to later improvements.
Meta-analysis of four RCTs combining 118 participants found no significant improvement in ADHD symptoms for tDCS over sham-TDCS at follow-up. This held true for both the right and left prefrontal cortex, with no sign of either publication bias or heterogeneity.
Meta-analysis of five studies totaling 148 participants likewise found no improvement in inattention symptoms or hyperactivity symptoms for tDCS over sham-TDCS at follow-up. AS before, this was true for both the right and left prefrontal cortex, with no sign of either publication bias or heterogeneity.
The only positive results came from meta-analysis of the same five studies, which reported a medium effect size improvement in impulsivity symptoms at follow-up. Closer examination showed no improvement from stimulation of the right prefrontal cortex, but a large effect size improvement from stimulation of the left prefrontal cortex.
Interpretation:
It is important to note that the one positive result was from three RCTs combining only 90 children and adolescents, a small sample size. Moreover, when only one of sixteen combinations yields a positive outcome, that begins to look like p-hacking for a positive result.
In research, scientists use something called a “p-value” to determine if their findings are real or just due to chance. A p-value below 0.05 (or 5%) is considered “statistically significant,” meaning there's less than a 5% chance the result happened by pure luck.
When testing twenty outcomes by this standard, one would expect one to test positive by chance even if there is no underlying association. In this case, one in 16 comes awfully close to that.
To be sure, the research team straightforwardly reported all sixteen outcomes, but offered an arguably over-positive spin in their conclusion: “Our study only showed tDCS-associated impulsivity improvement in children/adolescents with ADHD during follow-ups and anode placement on the left PFC. ... our findings based on a limited number of available trials warrant further verification from large-scale clinical investigations.”
Children and adolescents with ADHD tend to be less active and more sedentary than their typically developing peers. This is concerning, since physical activity benefits mental, physical, and social development. For youth with ADHD, being active can improve symptoms like inattention, working memory, and inhibitory control.
A major barrier to physical activity for children and adolescents with ADHD is limited motor competence. This stems from challenges in developing basic motor skills and more complex abilities needed for sports and advanced movements.
Difficulties in developing fundamental movement skills – such as locomotor (running, jumping), object-control (throwing, catching), and stability skills (balancing, turning) – can reduce motor competence and limit physical activity. These basic movements are learned and refined with practice and age, not innate abilities.
To date, research on the link between ADHD and motor competence has remained inconclusive. This systematic review and meta-analysis by a Spanish research team therefore aimed to determine whether children and adolescents with ADHD differ in motor competence from those with typical development (TD).
Studies had to include children and adolescents diagnosed with ADHD. They had to involve a full motor assessment battery, not just one test, and present motor competence data for both ADHD and TD groups.
The team excluded studies involving participants with other neurodevelopmental disorders or cognitive impairments, unless separate data for the ADHD subgroup were reported.
Meta-analysis of six studies combining 323 children and adolescents found that typically developing individuals were twelve times more likely to score in the 5th percentile of the Movement Assessment Battery for Children as their peers diagnosed with ADHD. They were also three times more likely to score in the 15th percentile (five studies, 289 participants). Results were consistent across the studies (low heterogeneity). All included studies were randomized.
Meta-analysis of five studies totaling 198 participants using the Test of Gross Motor Development reported significant deficits in both locomotor skills and object control skills among children and adolescents diagnosed with ADHD relative to their typically developing peers. In this case, however, results were inconsistent across studies (very high heterogeneity), and one of the studies was unrandomized. Because the team published only unstandardized mean differences, there was no indication of effect sizes.
Meta-analysis of two studies encompassing 164 participants using the Bruininks-Oseretsky Test of Motor Proficiency similarly yielded significant deficits among children and adolescents diagnosed with ADHD relative to their typically developing peers, but in this case with low heterogeneity. Notably, one of the two studies was not randomized.
Moreover, the team made no assessment of publication bias.
The team concluded, “The findings of this review indicate that children and adolescents with ADHD show significantly lower levels of motor competence compared to their TD peers. This trend was evident across a range of validated assessment tools, including the MABC, BOT, TGMD, and other standardized test batteries. Future research should aim to reduce methodological heterogeneity and further investigate the influence of factors such as ADHD subtypes and comorbid conditions on motor development trajectories.”
However, without a publication bias assessment, reliance on unrandomized studies in two of the tests, no indication of effect size in the same two tests, and small sample sizes, these results are at best suggestive, and will require further research to confirm.
Executive function impairment is a key feature of ADHD, with its severity linked to the intensity of ADHD symptoms. Executive function involves managing complex cognitive tasks for organized behavior and includes three main areas: inhibitory control (suppressing impulsive actions), working memory (holding information briefly), and cognitive flexibility (switching between different mental tasks). Improving executive functions is a critical objective in the treatment of ADHD.
Amphetamines and methylphenidate are commonly used to treat ADHD, but can cause side effects like reduced appetite, sleep problems, nausea, and headaches. Long-term use may also lead to stunted growth and cardiovascular issues. This encourages the search for non-invasive methods to enhance executive function in children with ADHD.
Neurological techniques like neurofeedback and transcranial stimulation are increasingly used to treat children with neurodevelopmental disorders. Neurofeedback is the most adopted method; it is noninvasive and aims to improve brain function by providing real-time feedback on brainwave activity so participants can self-regulate targeted brain regions.
The systematic search and meta-analysis examined children and adolescents aged 6–18 with ADHD. It included randomized and non-randomized controlled trials, as well as quasi-experimental studies that reported statistical data such as participant numbers, means, and standard deviations. Studies were required to use validated measures of executive function, including neurocognitive tasks or questionnaires. They also had to have control groups.
A meta-analysis of ten studies (539 participants) found a small-to-medium improvement in inhibitory control after neurofeedback training, with no publication bias and minimal study heterogeneity*. Long-term treatment (over 21 hours) showed benefits, while short-term treatment did not. However, publication bias was present in the long-term treatment studies and was not addressed.
A meta-analysis of seven studies with 370 children and adolescents found a small-to-medium improvement in working memory after neurofeedback, with no publication bias overall but high heterogeneity. A dose-response effect was observed: treatments over 21 hours showed benefits, while shorter ones did not. However, publication bias was present in the long-term treatment studies and was not addressed.
The study team also looked at sustained effects six months to a year after conclusion of training. Meta-analysis of two studies totaling 131 participants found a sustained small-to-medium improvement in inhibitory control, with negligible heterogeneity. Meta-analysis of three studies combining 182 participants found a sustained medium improvement in working memory, with moderate heterogeneity and no sign of publication bias.
The team concluded, “NFT is an effective intervention for improving executive function in children with ADHD, specifically inhibitory control and working memory. This approach demonstrates a more pronounced impact on working memory when extended beyond 1000 min [sic], with inhibitory control following closely behind. Furthermore, the evidence suggests that NFT may have sustained effects on both working memory and inhibitory control. Given the relatively small number of studies assessing long-term effects and the potential for publication bias, further research is necessary to confirm these effects.”
Moreover, because 1) RCTs are the gold standard, and the meta-analyses combined RCTs with non-RCTs, and 2) data from neurocognitive tasks was combined with data from more subjective and less accurate questionnaires, these meta-analysis results should be interpreted with further caution.
*Heterogeneity refers to the rate of variation between individual study outcomes. High heterogeneity means that there was substantial variation in the results. When a meta-anaylysis has high heterogeneity, it suggests that the studies differ significantly in their populations, methods, interventions, or outcomes, making the combined result much less reliable.
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