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May 16, 2025

Seven New Meta-analyses Suggest Wide Range of Benefits from Exercise for Persons with ADHD

Seven New Meta-analyses Suggest Wide Range of Benefits from Exercise for Persons with ADHD

ADHD is associated with deficits in executive functions. These are mental processes that enable individuals to plan, focus attention, manage tasks, and regulate emotions. These skills encompass working memory, cognitive flexibility, and inhibitory control, which are crucial for goal-directed behavior and decision-making. 

Working memory, which temporarily stores and processes information, contributes to language development by helping individuals make sense of what they read or hear.  

Cognitive flexibility refers to the ability to change perspectives, adapt thinking strategies, adjust to changing needs and priorities, recognize errors, and grasp opportunities.  

Inhibition switching involves intentional control of attention and emotions, suppressing automatic responses when necessary to prevent inappropriate behavior.  

These elements are critical to academic, social, and professional success. 

An international study team (Li et al.) conducted a meta-analysis of randomized controlled trials (RCTs) to explore the efficacy of physical activity for improving executive functions among children with ADHD aged 6 to 12. 

Meta-analysis of eleven RCTs encompassing 388 children reported a medium-to-large effect size improvement in cognitive flexibility. However, it found no benefit from aerobic exercise (such as running, jumping). When limited to the nine studies with 301 children that focused on cognitively engaging exercise (such as soccer and water sports that require constant monitoring of other players and strategizing), it found a large effect size improvement. Correcting for possible publication bias had no effect on the outcome. 

Meta-analysis of nine RCTs totaling 398 children reported a large effect size improvement in working memory. Once again, it found no benefit from aerobic exercise. Focusing on the seven RCTs with 288 children that used cognitively engaging exercise, it found a very large effect size improvement. There was no sign of publication bias. 

Meta-analysis of fourteen RCTs combining 579 children reported a small-to-medium effect size improvement in inhibition switching. But whereas it found a medium effect size improvement for shorter interventions of less than an hour (eight RCTs, 334 children), it found no benefit from interventions lasting an hour or more (six RCTs, 245 children. Again, there was no sign of publication bias. 

The team concluded, “Our study shows that physical activity interventions have a positive effect on improving executive function in school-age children with ADHD, with cognitive-engaging exercises showing greater benefits across three executive function measures.” 

A Chinese study team (Yang et al.) performed a related meta-analysis on the effect of exercise on inhibitory control in adults. Combining eight RCTs with a total of 372 participants, it reported a very large effect size improvement in inhibitory control, primarily from regular exercise. However, the effects were heavily influenced by a couple of outliers. The team claimed to have performed a sensitivity analysis but offered no evidence. Likewise, they noted signs of publication bias but did not use the standard trim-and-fill analysis to correct for it. 

Another Chinese study team (Xiangqin Song et al.) examined the effect of exercise on working memory in children and adolescents.  

Meta-analysis of 17 RCTs encompassing 419 participants found a medium effect size improvement in working memory. The large effect size improvement for cognitive aerobic exercise (4 RCTs, 233 participants) was twice the effect size for simple aerobic exercise (8 RCTs, 397 participants), though this meta-analysis still found a small-to-medium effect size gain from the latter. There was no sign of publication bias.  

The team concluded, “The results indicate that cognitive-aerobic exercise and ball sports are significantly more effective than other types of exercise interventions in improving working memory. This difference may be attributed to the varying cognitive load, task complexity, and the degree of activation of executive functions across different exercise types. The findings suggest that when designing exercise interventions for children with ADHD, priority should be given to exercise types with higher cognitive load in order to more effectively enhance working memory.” 

A joint Australian-U.S. team (Singh et al.) conducted a meta-meta-analysis on the effect of exercise on executive functions, that is, a meta-analysis of previous meta-analyses of RCTs.  

Combining ten separate meta-analyses with well over 2,800 children and adolescents with ADHD, it reported large effect size improvements in executive functions overall. There was no further breakdown by type of executive function and type of physical activity.  

The team concluded, “While exercise was seen to have a moderate and similar positive impact across all populations with respect to general cognition and memory, benefits for executive function were particularly marked in individuals with ADHD. This subgroup was unique in demonstrating a large effect size. This could be attributed to the task selection and the fact that many ADHD studies involved children. While the exact reason for this finding is unclear, there is evidence to suggest that impairments in executive function are common among individuals with ADHD. As such, it is plausible that this population may have a greater capacity for improvement due to starting from a lower baseline, compared with those with ‘normal’ executive function.” 

Another Chinese study team (Yagang Song et al.) performed a meta-analysis of RCTs examining the effects of physical exercise on anxiety, depression, and emotion regulation among children and adolescents with ADHD.  

Meta-analysis of eleven studies with a combined total of 384 participants reported a medium effect size reduction in symptoms of anxiety, with a dose-effect response. Physical exercise once a week had no significant effect, while twice a week was associated with a medium effect size reduction, and three or more times a week with a very large effect size improvement. Moderate intensity exercise was three times more effective than low intensity exercise.  

Meta-analysis of seven studies encompassing 187 individuals similarly reported a medium effect size reduction in symptoms of depression. Once again, moderate intensity was far more effective than low intensity exercise. 

Meta-analysis of seven studies totaling 429 children and adolescents reported a very large effect size improvement in emotion regulation, especially for physical exercise conducted at least twice a week

There was no sign of publication bias in the anxiety, depression, or emotion regulation findings. 

The team concluded, “Physical exercise demonstrated a substantial overall impact on enhancing anxiety, depression, and emotional regulation in children with ADHD, exhibiting a dose-response effect correlated with the period, frequency, duration, and intensity of the exercise. This investigation ... presents an additional evidence-based therapeutic approach for the considerable number of children with ADHD who are not appropriate candidates for pharmacological intervention.” 

A joint U.S.-Hong Kong study team (Liu et al.) performed a meta-analysis exploring the effect of physical exercise on motor proficiency. Motor proficiency includes both gross motor skills (like walking and running) and fine motor skills (like writing and buttoning).  

Meta-analysis of ten studies encompassing 413 children and adolescents with ADHD reported a very large effect size improvement in motor proficiency from physical exercise. The gains for object control, fine manual control, and manual coordination were roughly twice the gains for body coordination. There was no sign of publication bias. 

Finally, a Spanish research team (González-Devesa et al.) conducted a meta-analysis examining the effect of exercise on objectively measured sleep status among persons with ADHD. 

Meta-analysis of three RCTs with a combined total of 131 individuals that used accelerometers to measure sleep duration reported no significant effect one way or the other from exercise

The team concluded, “The existing evidence regarding the use of exercise to manage sleep problems in individuals with ADHD remains inconclusive. Preliminary findings from this review suggest a potential positive effect of exercise on self-reported sleep quality; however, its efficacy in improving sleep duration could not be confirmed.” 

The Take-Away:

An ideal exercise regimen for children with ADHD should focus on cognitively engaging physical activities rather than simple aerobic exercise. Sports and activities that require strategic thinking, attention to others’ actions, and rapid decision-making—such as soccer, martial arts, or water-based team sports—gave the best results, especially for working memory and cognitive flexibility. These types of exercise also show strong benefits for emotional regulation, reducing anxiety and depression, and enhancing motor proficiency.

To maximize benefits, the regimen should include moderate-intensity sessions at least two to three times per week, each lasting less than an hour, as longer durations appear less effective for improving inhibitory control. This structured, cognitively demanding approach offers an evidence-based, non-pharmacologic treatment option for children with ADHD, particularly for those who cannot or prefer not to use medication.  We need, however, more work to determine if exercise will provide the same symptom reduction and protection from adverse outcomes as has been shown for medications.

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Meta-analyses Suggest Physical Exercise is Effective Tool in Treating ADHD

Two meta-analyses suggest physical exercise is an effective tool in treating ADHD

Two recent meta-analyses, one by an Asian team, and the other by a European team, have reported encouraging results on the efficacy of physical exercise in treating ADHD among children and adolescents.

One, a Hong Kong-based team (Liang et al. 2021) looked at the effect of exercise on executive functioning.

The team identified fifteen studies with a combined total, of 493 participants that met the criteria for inclusion. As the authors noted, "only a few studies successfully blinded participants and therapists, due to the challenges associated with executing double-blind procedures in non-pharmacological studies."

After adjusting for publication bias, the meta-analysis of the fifteen studies found a large improvement in overall executive functioning.

The studies varied in which aspects of executive functioning were addressed. A meta-analysis of a subset of eleven studies encompassing 406 participants found a large improvement in inhibitory control. A meta-analysis of another subset, of eight studies with a total of 311 participants, found a large improvement in cognitive flexibility. Finally, a meta-analysis of a subset of five studies encompassing 198 participants found a small-to-medium improvement in working memory.

Nine studies involved acute (singular) exercise interventions lasting 5 to 30 minutes, while twelve studies involved chronic (regular) exercise interventions ranging from 6 to 12 weeks, with a total duration of 12 to 75 hours. The chronic exercise was more than twice as effective as acute exercise. The former resulted in large improvements in overall executive functioning, the latter in small-to-medium improvements.

No significant differences were found between aerobic exercises (such as running and swimming) and cognitively engaging exercises(such as table tennis and other ball games, and exergaming ... video games that are also a form of exercise, relying on technology that tracks body movements).

The authors concluded that "Chronic sessions of exercise interventions with moderate intensity should be incorporated as a treatment for children with ADHD to promote executive functions."

Meanwhile, a German study team (Seiffer et al. 2021) looked at the effects of regular, moderate-to-vigorous physical activity on ADHD symptoms in children and adolescents.

They found eleven studies meeting their criteria, with a combined total of 448 participants. A meta-analysis of all eleven studies found a small-to-moderate decline in ADHD symptoms. However, the three studies with blinded outcome assessors found a large and statistically highly significant decline in symptoms, whereas the eight studies with blinded outcome evaluators found only a small decline that was not statistically significant.

When compared with active controls using pharmacotherapy in a subgroup of two studies with 146 participants, pharmacotherapy held a small-to-moderate advantage that fell just short of statistical significance, most likely because of the relatively small sample size.

The authors concluded that moderate to vigorous physical activity (MVPA) "could serve as an alternative treatment for ADHD," but that additional randomized controlled trials "are necessary to increase the understanding of the effect regarding frequency, intensity, type of MVPA interventions, and differential effects on age groups."

December 5, 2021
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Parents of Children With ADHD at Higher Risk for Traumatic Injury

Nationwide population study finds higher risk of traumatic injury among parents of children with ADHD

Previous population studies have shown that children with ADHD have a much higher risk of traumatic injuries than their normally developing peers, and that such risk can be greatly reduced with methylphenidate treatment.

But what about the parents of children with ADHD? How does their risk compare with that of parents of normally developing children?

Taiwan has a single-payer public health insurance system that maintains comprehensive healthcare records of virtually every resident.

A Taiwanese research team availed itself of the Taiwan Maternal and Child Health Database, which covers 99.8% of all births, to identify 81,401 fathers and 87,549 mothers who had at least one offspring with ADHD and 1,646,100 fathers and 1,730,941 mothers with no offspring with ADHD.

The team determined children's ADHD status based on either an inpatient diagnosis or four or more  diagnoses.

It looked for parental traumatic injuries including burn injury, fracture, and traumatic brain injury.

To address covariates, it adjusted for age, urbanicity, low-income level, and competing risk of death.

Adjusted for those covariates, parents of children with ADHD were 20% more likely to suffer bone fractures, 27% more likely to have traumatic brain injuries, and 30% more likely to have burn injuries requiring medical treatment than parents of normally developing children.

The elevated risks were significant across the board, but roughly twice as much s for mothers as for fathers of children with ADHD - up 30% vs 15% for bone fractures, up 35% vs 23% for burn injuries, and up 45% vs 21% for traumatic brain injuries.

The authors noted that ADHD is highly heritable and that the findings may in part point to undiagnosed adult ADHD.

Another contributing factor, they suggested, is that "studies have revealed that a high proportion of parents having children with ADHD experience depression and anxiety. Stress-related negative emotions (depression and anxiety) were shown to cause loss of concentration, thereby increasing the likelihood of accidental events such as traffic accidents and contributing to the increased risks of traumatic injury among parents of children  ADHD."

The much-higher elevated risk for mothers seems to support this hypothesis, because mothers continue to be the principal caregivers in Taiwan, and are thus more exposed to the behaviors of their children. The authors cited a study indicating that "diagnosis of ADHD for children was reported to be a predictor of increased caregiver burden."

They concluded, "Given that knowledge is fundamental to act, it is essential to educate the parents of children with ADHD on the increased risk of traumatic injuries they may have. ... The need for behavioral and pharmacological intervention in parents of children with ADHD should be evaluated, especially in the parents with undiagnosed ADHD or sub-threshold ADHD symptoms. It deserves further prospective studies with longer follow-up periods to explore whether undiagnosed ADHD, care burden of parents, and children's aggressive behaviors contribute to the increased risks of traumatic injuries in parents of children with ADHD."

December 7, 2023
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Swedish Twin Study Finds Association Between Diet and ADHD

Associations between diet and ADHD emerge from Swedish population-based twin study

Sweden has a national single-payer health insurance system that includes virtually the entire population. It also has a system of national registers that track every resident from birth to death. That makes it possible to conduct nationwide population studies with a very high degree of precision and reliability.

In addition, one of the national registers is the Swedish Twin Register. Tracking all twins in the population enables studies to evaluate the degree to which observed associations may be attributable to genetic influences and to familial confounding. The twin method relies on the different levels of genetic relatedness between monozygotic ("identical") twins, who are genetically identical, and dizygotic ("fraternal") twins, who share on average half of their genetic variation (as do ordinary full siblings).

A Swedish team of researchers identified 42,582 Swedish twins born between 1959 and 1985, and who were, therefore, adults by the time of the study (20-47 years old). Of these, 24,872 (three out of five) completed a web-based survey with 1,300 questions covering lifestyle and mental and physical health. Out of this group, 17,999 provided information on ADHD symptoms and food frequency.

Self-reported ADHD symptoms came from nine inattention components and nine hyperactivity/impulsivity components, covering the 18 DSM- IV symptoms of ADHD.

The food frequency questionnaire included 94 food items, with the following frequency categories: never, 1-3 times/month, 1-2 times/week, 3-4 times/week, 5-6 times/week, 1 time/day, 2 times/day, 3 times/day.

In the raw data, the two subtypes of ADHD exhibited very similar associations. Both had significant associations with unhealthy diets. Both were more likely to be eating foods high in added sugar, and neglecting fruits and vegetables while eating more meat and fats.

After adjusting for the degree of relatedness of twins (whether monozygotic or dizygotic) and controlling for the other ADHD subtype, the associations remained statistically significant for inattention, but diminished to negligible levels or became statistically non-significant for hyperactivity/impulsivity.

Even for persons with inattention symptoms, adjusted correlations were small (never exceeding r = 0.10), with the strongest associations being for overall unhealthy eating habits (r = 0.09), eating foods high in added sugar (r = 0.10) or high in fat (r = 0.05), and neglecting fruits and vegetables (r = 0.06). All other associations became statistically non-significant.

For persons with hyperactivity/impulsivity symptoms, the only associations that remained statistically significant ­- but at tiny effect sizes - were unhealthy dietary patterns (r = 0.04) and consumption of foods high in added sugar (r = 0.03).

The further genetic analysis, therefore, focused on the strongest associations, between ADHD subtypes on the one hand, and unhealthy dietary patterns and eating foods high in added sugar on the other hand. The heritability estimates (the fraction of phenotypic covariance explained by genetic influences) were 44%, 40%, and 37% for inattention and high-sugar food, inattention and unhealthy dietary patterns, and hyperactivity/impulsivity and high-sugar food, respectively.

 When examining only differences between pairs of monozygotic("identical") twins, the correlations became stronger for inattention, rising to r = 0.12 for unhealthy eating habits and r = 0.13 for consumption of foods high in added sugar. For hyperactivity/impulsivity symptoms, the association with unhealthy eating habits was weaker, and the association with consumption of foods high in added sugar became statistically insignificant.

The authors concluded, "we identified positive associations between self-reported trait dimensions of ADHD and intake of seafood, high-fat food, high-sugar food, high-protein food, and an unhealthy dietary pattern, and negative associations with consumption of fruits, vegetables, and a healthy dietary pattern. However, all the associations are small in magnitude. These associations were stronger for inattention compared to hyperactivity/ impulsivity. This pattern of associations was also reflected at the etiological level, where we found a slightly stronger genetic correlation between inattention with dietary habits and hyperactivity/impulsivity with dietary habits. Non-shared environmental influences also contributed to the overlap between ADHD symptom dimensions and consumption of high-sugar food and unhealthy dietary pattern. However, shared environmental influences probably contributed relatively little to the associations between ADHD symptoms and dietary habits. ... significant MZ twin intraplate differences also provided support for a potential causal link between inattention and dietary habits.

November 29, 2021
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Taiwanese population study finds reduced risk of influenza among children on sustained methylphenidate treatment, but there's a big catch

Taiwanese population study finds reduced risk of influenza among children on sustained methylphenidate treatment, but there's a big catch

While influenza normally only threatens the elderly or those with complicating conditions, the 2009 H1N1 variant struck children particularly hard.

ADHD is known to be associated with inflammatory and immune-related disorders such as asthma, eczema, and allergic rhinitis. These disorders can aggravate respiratory infections such as influenza. Moreover, the cognitive deficits characteristic of ADHD - difficulty following instructions, reduced ability to control impulsive behavior and resulting nail-biting, and poor hand hygiene - can increase the probability of infection in the first place.

A Taiwanese research team explored how drug treatment for ADHD might affect the risk of childhood influenza. Only two drugs are approved in Taiwan for treating ADHD: the stimulant methylphenidate (MPH) and the non-stimulant atomoxetine. Because the latter is only recommended for patients who have unsatisfactory outcomes with MPH, MPH is the drug used in the vast majority of cases.

Taiwan is one of the relatively few countries that track the health care of its entire population in a comprehensive database, thanks to a single-payer health care system launched in1995. From the National Health Insurance Research Database, the Bureau of National Health Insurance in 2005 used random sampling to create a million-person Longitudinal Health Insurance Database (roughly five percent of the population).

From this latter database, the research team identified 9,826 patients newly diagnosed with ADHD. They excluded 1,786 with influenza before their ADHD diagnosis. After further excluding those outside the youth age brackets or who had gotten a flu shot during the year preceding enrollment, they were left with 5,259 patients with ADHD under age 18. Of these, 661 got influenza following diagnosis of ADHD.

In this ADHD cohort, 43 percent had not used any medication. Of the 57% who used medication, 20 percent did so for 90 days or less, and 37 percent for over 90 days.

After controlling for gender, age, level of urbanization, psychiatric or physical illnesses, and other medication use(sedative/hypnotics/anxiolytics), those prescribed MPH over 90 days were 38 percent less likely to get influenza requiring interaction with the health care system. There was a lesser reduction for those taking MPH 90 days or less, but it was not statistically significant.

A significant limitation is the fact that data from in-school vaccination programs are not included in the database used. If children receiving less or no medication were also less likely to be vaccinated, this unexplored covariate could explain the results. Further study is needed.

November 2, 2023
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Is there an association between childhood celiac disease and subsequent ADHD?

Is there an association between childhood celiac disease and subsequent ADHD?

Celiac disease is an autoimmune disorder triggered by dietary gluten in genetically predisposed individuals. Gluten is a protein found in wheat and related grains such as barley and rye. The disease affects one to two percent of Western populations.

An international team of physicians conducted a nationwide cohort study of the Swedish population to explore the relationship between childhood celiac disease and subsequent psychiatric disorders, including ADHD, as well as suicide attempts and suicide.

With data from all 28 pathology departments in Sweden, they identified all 19,186 children with a diagnosis of biopsy-verified celiac disease from 1973 through 2016, and no previous history of psychiatric disorder. They then matched them with 94,249 children controls matched for age, sex, county, and calendar year from the Swedish national registers that encompass the entire resident population.

To address shared intrafamilial confounding, including genetic and early environmental factors, the team also compared 13,015 individuals with celiac disease with their 18,024 non-celiac siblings.

Additional Swedish national registers (Patient Register, Cause of Death Register) then made it possible to link the preceding data with data on subsequent psychiatric disorders and suicides for all the children in the study.

Celiac disease diagnosed in childhood was associated with a 19 percent higher risk of any subsequent psychiatric disorder at any time than for controls. The greatest spike in risk - 70 percent higher than for non-celiac controls - was in the first year following diagnosis of celiac disease. Restricting follow-up until the age of 18 years, celiac disease was linked to a 26 percent increased risk of any psychiatric disorder. For adults 18 and over, the increased risk declined to just 11 percent. So an initial sharp spike was followed by a steeply declining curve over time.

For ADHD, the increased risk at any time after the diagnosis of celiac disease was 29 percent. That compares with 47 percent for autism spectrum disorder, 34 percent for eating disorders, 20 percent for mood disorders, and 12 percent for anxiety disorders. There was no increased risk of psychotic disorders, behavioral disorders, personality disorders, psychoactive substance abuse, suicide attempts, or suicide. For adults 18 and over, however, the increased risk of ADHD rose to 39 percent, second only to autism spectrum disorder. For these two psychiatric conditions, there was an upward curve rather than a declining one.

The sibling analyses found a reduced but still significant 12 percent increased risk of psychiatric disorder following a diagnosis of celiac disease, again with the first-year spike of 48 percent increased risk declining to insignificance for the period beginning five years later. For ADHD, the increased risk also descended to 12 percent, but became non-significant, suggesting the increases were primarily attributable to confounding variables.

Among the 2,071 children with celiac disease who had a follow-up biopsy that showed mucosal healing of the small intestine in response to a gluten-free diet, the association with subsequent psychiatric disorders vanished.

The authors speculated that the spike in psychiatric diagnoses in the year following diagnosis of celiac disease could be because "the systemic inflammatory response is mediating this relationship," or could be due to "the psychosocial stress associated with adapting to the gluten-free diet." "However," they cautioned, "this risk is unlikely to be due to the gluten-free diet alone since we also observed an increased risk of psychiatric disorders preceding the diagnosis of celiac disease, possibly related to the systemic inflammatory response described above."  We must also keep in mind that such studies cannot rule out all sources of confounding or the possibility that being diagnosed with celiac disease leads to more exposure to the healthcare system and more opportunities for a diagnosis of ADHD to be recognized.

November 20, 2023
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Swedish countrywide population study concludes that neonatal jaundice is not tied to ADHD

Swedish countrywide population study concludes that neonatal jaundice is not tied to ADHD

Bilirubin is an orange-yellow pigment formed in the liver by the breakdown of hemoglobin and excreted in bile. Elevated levels in blood serum can cause jaundice, a yellowing of the skin, or whites of the eyes.

More than one in twenty Swedish newborns are treated for neonatal jaundice, which is particularly common among preterm babies. It is usually benign.

A team of Swedish researchers used e Swedish Medical Birth Register, which contains information on all children born in the country, to identify all 814,420 single births without birth defects between 1992 and 2000, and followed them until 2009. They then identified instances of neonatal jaundice and of ADHD through linked nationwide medical registers.

The team also identified a sub-sample of full siblings (384,290 children from 181,354 families) in order to control for shared familial traits.

In the unadjusted results, children with any kind of neonatal jaundice were 38% more likely to be diagnosed with ADHD. After adjustment for known confounding variables, two-thirds of the association disappeared, with a residual increased risk of 13%.

There are, however, two types of neonatal jaundice: hemolytic and non-hemolytic. Hemolytic jaundice is typically caused by the mother's immune system mistaking the fetus' red blood cells as a threat, and responding by attacking with antibodies, rupturing and destroying the cells.

The study found no association between hemolytic jaundice and ADHD, either in the raw results or after adjusting for known confounders. Unsurprisingly, there was also no association in the sibling comparison.

That meant that all the association was concentrated among children born with non-hemolytic jaundice, who in the crude results were 43% more likely to subsequently develop ADHD. Adjusting for known confounders again reduced the association by two-thirds, to 14%. But among siblings, that association vanished altogether. Children born with non-hemolytic jaundice were no more likely than their non-jaundiced siblings to develop ADHD.

The authors concluded that "neonatal jaundice is not likely a causal risk factor for ADHD."

December 14, 2023
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Safety of Long-term Methylphenidate Treatment of Adults with ADHD

Safety of long-term methylphenidate treatment of adults with ADHD

The Comparison of Methylphenidate and Psychotherapy in adult ADHD Study (COMPAS) was a prospective, randomized multicenter clinical trial, comparing methylphenidate (MPH) with placebo in combination with cognitive-behavioral group psychotherapy or (GPT) individual clinical management (CM), the latter two being active controls. This was a year-long trial.

The German study team randomly assigned 433 participants with adult ADHD to each of the four study groups. As this was a 2 x 2 matrix trial, each study group included both one pharmacological intervention (MPH or placebo) and one psychological intervention (GPT or CM).

GPT included mindfulness training, skills for stress management, emotion regulation, and time management as well as behavioral analyses. CM sessions focused on participants' current concerns and medication.

As is usual in such trials, the number of participants decreased throughout the study as some individuals dropped out. At 13 weeks, 337 participants were still taking their study medication.

Both MPH and placebo were started at 10 mg doses, then up-titrated depending on clinical response. After 13 weeks, the mean MPH dose had risen to 50 mg, and the mean dose of placebo to 58 mg.

Safety

Among those taking MPH, 96 percent of participants reported at least one adverse event. Among those on placebo, the equivalent figure was 88 percent.

The principal adverse events occurring significantly more frequently in the MPH group were decreased appetite (22 vs. 3.8 %), dry mouth (15 vs. 4.8 %), palpitations (13 vs. 3.3 %), gastrointestinal infection (11 vs. 4.8 %), agitation (11 vs. 3.3 %), restlessness (10 vs. 2.9 %), excessive sweating, rapid heartbeat, and weight decrease (all 6.3 vs. 1.9 %).

The only adverse event that occurred significantly more frequently in the placebo group was a temporary loss of consciousness caused by a fall in blood pressure (2.4 vs. 0%).

Serious adverse events were infrequent in both groups, affecting 7.3 percent of those in the MPH group and 4.3 percent of those in the placebo group. The difference between groups was not statistically significant. There were no deaths.

While patients on MPH lost an average of 1.2 Kg during the year, those on placebo remained constant (gained 0.3 Kg). Changes in blood pressure were negligible in both groups. Average heart rate rose by 3 beats per minute in the MPH group, versus a 1 beat per minute decline in the placebo group. There were no significant differences in clinically relevant electrocardiogram abnormalities between the two treatment groups.

Turning to psychological interventions, 90 percent of participants in the GPT group and 94 percent in the CM group experienced at least one adverse event. Differences between the two groups were not statistically significant. Serious adverse events occurred in 3.9% of the GPT participants and 7.7 percent of the CN participants, but again the difference between groups was not statistically significant. There were no clinically relevant changes in weight, blood pressure, or heart rates in these groups throughout the study.

The study team found no modulating effects of either form of psychological treatment on the distribution of adverse events under MPH and placebo treatment.

The authors concluded, "adverse events were found more frequently in patients receiving MPH compared to placebo and were mostly attributable to the centrally stimulating and sympathomimetic action of MPH, including agitation, restlessness, dry mouth, decreased appetite, palpitations, tachycardia [rapid heartbeat], and hyperhidrosis [excessive sweating]. About these adverse events, a causal relationship with MPH seems likely, supported by both the pharmacological effects of MPH as well as previous safety data. ... It is important to note that patients receiving MPH in COMPAS significantly profited from the medication about the reduction of ADHD symptom load, thus the risks of adverse events have to be weighed against the clear benefits. ... Premature termination of MPH due to an adverse event as major reason occurred in less than 10 % of patients and was not statistically significantly different from placebo."

November 21, 2021
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How social disadvantages affect risk of ADHD

How social disadvantages affect risk of ADHD

Danish health care is universal and free. That means there is very complete data available that covers the entire population. The health registers are linked to other national registers that provide access to socioeconomic information. That offers unusual opportunities to research correlations across an entire national population.

Moreover, the health care system requires a high standard for diagnosis of ADHD - evaluation by specialist doctors or psychiatrists rather than a general practitioner. An exception is when parents seek a diagnosis from a private practicing child psychiatrist, in which case diagnostic registration is not mandatory and data is therefore incomplete.

A trio of Danish researchers used the country' national registers to conduct a nationwide population cohort study to explore the cumulative effects of social disadvantages as risk factors for being diagnosed with ADHD.

They looked at all 632,725 children born in Denmark during the 1990s, of which 23,287 (3.7 percent) either had a registered diagnosis in the Patient Registry or else were undergoing ADHD treatment before age 18. Of these, 12,610 children had a registered ADHD diagnosis and entered medical treatment, 4,049 children had a registered diagnosis with no medical treatment, and 6,628 children entered medical treatment with no registered diagnosis. The latter were presumably diagnosed by private practicing psychiatrists. Adjustments were made for gender, immigrant status, birth characteristics (weight, gestational age), single-parenthood, parent ADHD diagnosis, and the number of children in the household.

The study determined that parental educational attainment had the largest effect on the risk of ADHD. Having parents who completed no more than the minimum compulsory education was associated with a 3.5 percentage point higher risk of getting an ADHD diagnosis. Completing no more than upper secondary education was associated with a 1.3 percent higher risk. But there was a sharp bifurcation in the two alternative components of upper secondary education. Children of parents who completed a vocational track faced a 1.7 percent increase in risk, whereas those whose parents completed a college preparatory track faced a negligible 0.17 percent increase.

Parental unemployment also had a significant effect. Youths whose parents were unemployed most of the year faced a 2.1 percent higher risk of ADHD, whereas those whose parents were unemployed less than half the year faced a 1.3 percent higher risk.

Relative income poverty had a comparable impact. Children of parents in the lowest income quintile faced a 2.3 percent higher risk of ADHD than those of parents in the uppermost income quintile. Those in the second-lowest quintile faced a 1.9 percent higher risk than those in the uppermost quintile; those in the middle quintile a 1.3 percent higher risk, and those in the second-highest quintile a 0.8 percent higher risk.

All three cases showed a dose-response relationship, in which higher gradations of social disadvantage were associated with higher levels of risk.

Since these social disadvantages often overlap, the researchers looked at combinations as well and found them to be roughly additive in effect. Parental unemployment plus relative income poverty was associated with a 1.9 percent higher risk of offspring ADHD. Parental unemployment plus completion of no more than compulsory education was associated with a 3.2 percent higher risk. Parental relative income poverty plus completion of no more than compulsory education produced a 4.2 percent higher risk. Finally, Parental relative income poverty plus completion of no more than compulsory education plus unemployment was associated with a 4.9 percent higher risk.

The authors concluded, "This study shows that specific and well-measured parental social disadvantages in terms of unemployment, relative income poverty, and low educational attainment independently affect the risk of ADHD."

November 19, 2021
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Supplements Helping ADHD Symptoms: Anecdotal or Proven?

Meta-analysis claims effectiveness of multi-nutrient supplements in treating ADHD, but reports inconsistent results and has methodological shortcomings

A recently published meta-analysis compared the treatment of ADHD with multi-nutrient supplements versus placebo.

Children received either placebo or Daily Essential Nutrients(Vit A 384 IU, Vit C 40 mg, Vit D 200 IU, Vit E 24 IU, Vit K 8 μg, B1 4 mg, B21.2 mg, B3 6 mg, B6 4.67 mg, B9 50 μg, B12 60 μg, B7 72 μg, B5 2 mg, Ca 88 mg, Fe 0.92 mg, P 56 mg, I 13.6 μg, Mg 40 mg, Zn 3.2 mg, Se 13.6 μg, Cu 0.48 mg, Mn0.64 mg, Cr 41.6 μg, Mo 9.6 μg, P 16 mg. Proprietary blend: Choline bitartrate, Alpha-lipoic acid, Inositol, Acety-l-carnitine (as acetyl-L-carnitine hydrochloride), Grape seed extract, Ginkgo biloba leaf extract, Methionine (asL-methionine hydrochloride), Cysteine (as N-acetyl-L-cysteine), Germanium sesquioxide (as chelate), Boron, Vanadium, Lithium orotate, Nickel. Other ingredients: Cellulose glycine 45 mg, Citric acid 26.814 mg, Magnesium stearate24 mg, Silicon dioxide 20 mg).

Adults received either placebo or EMP+ (Vit A 5760IU, Vit C 600 mg, Vit D 1440 IU, Vit E 360 IU, B1 18 mg, B2 13.5 mg, B3 90 mg,B5 21.6 mg, B6 36 mg, B9 1440 μg, B12 900 μg, Biotin 1080 μg, Pantothenic acid21.6 mg, Ca 1320 mg, Fe 13.74 mg, P 840mg, I 204 μg, Mg 600 mg, Zn 48 mg, Se204 μg, Cu 7.2 mg, Mn 9.6 mg, Cr 624 μg, Mo 144 μg, K 240 mg, Germaniumsesquioxide 20.7 mg, B 2400 μg, V 1194 μg, Ni 29.4 μg, Choline bitartrate 540mg, DL-phenylalanine 360 mg, Citrus bioflavonoids 240 mg, Inositol 180 mg,Glutamine 180 mg, L-methionine 60 mg, Gingko biloba 36 mg, grape seed extract45 mg).

Using the Global Assessment of Functioning (GAF) scale for adults, and the Children's Global Assessment Scale (CGAS) for children, the study team reported moderate improvements in overall functioning from the use of the supplements. GAF and CGAF are used by mental health clinicians and physicians to rate subjectively the social, occupational, and psychological functioning of an individual.

Yet no significant improvements were found for either clinician-rated or observer-rated ADHD Change Scores.

Moreover, the positive finding was compromised by a series of methodological shortcomings:

·        It was just barely a meta-analysis, involving only two studies.
·        The combined number of participants in the two studies was small, 173, consisting of 93 children in one study and 80 adults in the other.
·        Both studies had the same lead author, Julia J. Rucklidge, who was also a member of the meta-analysis team.

With only two studies, there was no way to evaluate publication bias.

October 25, 2023
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Meta-analysis Finds Narrative Language Impairment in Youths with ADHD

Meta-analysis Finds Narrative Language Impairment in Youths with ADHD

Youths with ADHD are known to be more prone to language problems when compared with typically developing peers. To what extent does that affect their ability to share a narrative with others?

A Danish research team conducted a systematic review and meta-analysis of the peer-reviewed medical literature to explore this question. They stressed that this ability is important because "a narrative is a genre of discourse - a form of social communication used to derive meaning from experiences and to construct a shared understanding of events. In other words, it is the fundamental ability of orally producing a coherent story." They focused on the production of narratives rather than comprehension.

Studies had to have a minimum of 10 participants. They had to compare aspects of oral narrative production in children and adolescents with either a formal ADHD diagnosis or a score above a clinical cut-off on a validated ADHD rating scale to a control group of typically developing youths. Youths with confirmed autism spectrum disorder (ASD) or language impairment diagnoses were excluded. There were no constraints on IQ.

The team found sixteen studies with a combined total of 1,015 youths that met these criteria and were suitable for meta-analysis.

They examined seven aspects of oral narrative production:

·        Coherence: A story structure that is logical and easy to follow in cause and sequence. There is a clear beginning, middle, and end. There are goals, attempts, and outcomes. A meta-analysis of nine studies with a combined total of 750 participants found youths with ADHD less coherent than their typically developing peers, with a medium effect size. There was virtually no between-study heterogeneity and no sign of publication bias.
·        Cohesion: This ensures referencing of events and characters in a manner that enables the listener to grasp how characters, events, and ideas in a story are related. Ambiguous or contradictory references get in the way of this. A meta-analysis of eight studies with a combined total of 501 participants found youths with ADHD showed less cohesion than their typically developing peers, with a medium effect size. Again, with virtually no between-study heterogeneity, and no sign of publication bias.
·        Disruptions: These can be sequence errors, misinterpretations, embellishments, or confabulations - fabricating imaginary experiences as compensation for loss of memory. A meta-analysis of six studies with 389 participants found youths with ADHD had more disruptions than their typically developing peers, with a small-to-medium effect size. There was virtually no between-study heterogeneity and no sign of publication bias.
·        Fluency: Best explained in terms of errors that interfere with this quality, such as false starts, repeating words or sentences, and abandoning sentences without completing them. A meta-analysis of four studies with 220 participants found no difference in fluency between youths with ADHD and their typically developing peers.
·        Production: This is a measure of output -overall length of the story, number of sentences, number of words. After adjusting for evidence of publication bias, a meta-analysis of twelve studies with 645 participants found no difference here.
·        Syntactic complexity: This includes the extent of vocabulary and the use of proper grammar. A meta-analysis of six studies with 272 participants found youths with ADHD displayed less syntactic complexity than their typically developing peers, with a small-to-medium effect size. There was virtually no between-study heterogeneity and no sign of publication bi
·        Internal state language: References to perceptions, thoughts, beliefs, and feelings. There were only two studies with 130 participants, so no meta-analysis was performed.

The authors concluded, "the results from the current meta-analysis suggest that children with ADHD have impairments in their narrative language. In particular, children with ADHD produce narratives that are less coherent, less cohesive, less syntactically complex, and include more disruptive errors than typically developing children do."

December 4, 2023
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