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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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To what extent does ADHD affect sleep in adults, and in what ways?

To what extent does ADHD affect sleep in adults, and in what ways?

We are only beginning to explore how ADHD affects sleep in adults. A team of European researchers recently published the first meta-analysis on the subject, drawing on thirteen studies with 1,439 participants. They examined both subjective evaluations from sleep questionnaires and objective measurements from actigraphy and polysomnography. However, due to differences among the studies, only two to seven could be combined for any single topic, generally with considerably fewer participants (88 to 873).


Several patterns emerged. Looking at results from sleep questionnaires, they found that adults with ADHD were far more likely to report general sleep problems (very large SMD effect size 1.55). Getting more specific, they were also more likely to report frequent night awakenings(medium effect size 0.56), taking longer to get to sleep (medium-to-large effect size 0.67), lower sleep quality (medium-to-large effect size 0.69), lower sleep efficiency (medium effect size 0.55), and feeling sleepy during the daytime(large effect size 0.75).

There was little to no sign of publication bias, though considerable heterogeneity on all but night awakenings and sleep quality.


Actigraphy readings confirmed some subjective reports. On average, adults with ADHD took longer to get to sleep (large effect size 0.80) and had lower sleep efficiency (medium-to-large effect size 0.68). They also spent more time awake (small-to-medium effect size 0.40). There was little to no sign of publication bias and there was little heterogeneity among studies.


None of the polysomnography measurements, however, found any significant differences between adults with and without ADHD. All effect sizes were small (under 0.20), and none came close to being statistically significant.


There were four instances where measurement criteria overlapped those from actigraphy and self-reporting, with varying degrees of agreement and divergence. There was no significant difference in total sleep time, matching findings from both the questionnaires and actigraphy. On percent time spent awake, polysomnography found little to no effect size with no statistical significance, whereas actigraphy found a small-to-medium effect size that did not quite reach significance, and self-reporting came up with a medium effect size that was statistically significant. Sleep onset latency and sleep efficiency, for which questionnaires and actigraphy found medium-to-large effects, the polysomnography measurements found little to none, with no statistical significance.


Polysomnography found no significant differences in stage 1-sleep, stage 2-sleep, slow-wave sleep, and REM sleep. Except for slow-wave sleep, there was no sign of publication bias. Heterogeneity was generally minimal.


One problem with the extant literature is that many studies did not take medication status into account.

The authors concluded, "future studies should be conducted in medicatio- naïve samples of adults with and without ADHD matched for comorbid psychiatric disorders and other relevant demographic variables."


In summary, these findings provide robust evidence that ADHD adults report a variety of sleep problems.  In contrast, objective demonstrations of sleep abnormalities have not been consistently demonstrated.   More work in medication-naïve samples is needed to confirm these conclusions.

July 24, 2021
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Are Shared Care Models Effective in Treating Childhood ADHD?

Are Shared Care Models Effective in Treating Childhood ADHD?

A systematic review found five studies that evaluated shared care models involving children and adolescents, in which primary care providers(PCPs) collaborated with mental health care providers in treating ADHD. The 655 participants ranged in age from 5 to 17. Two of the studies were randomized.

In one, the largest, with 321 participants, care managers acted as liaisons between PCPs and psychiatrists and provided psychoeducation and skills training for families. Effect sizes on the Vanderbilt ADHD Diagnostic Teacher Rating Scale were very small, ranging from a standardized mean difference (SMDs) of 0.07 to 0.12. Improvement on the Clinical Global Impression scale was also small (SMD = 0.3)and was not significant (p = 0.4).

In the other randomized study, with 63 participants, care managers also acted as liaisons between PCPs and a psychiatric decision support panel to provide Positive Parenting Training. The SNAP-IV hyperactivity/impulsivity score showed a medium effect size (SMD = 0.7), with a medium-to-large effect size (0.7) for improvement in social skills. The score difference for SNAP-IV inattention was not statistically significant. The other three studies followed groups of individuals over time.

In one cohort with 129 participants, PSPs consulted with psychiatrists by telephone; an evaluation, where necessary, was performed within 4 weeks. As assessed by the Clinical Global Impression-Severity scale, symptoms declined from moderately severe to mild or borderline. On the Children's Global Assessment Scale, there was an improvement from problems in more than one area of functioning to just one area.

In another cohort with 116 participants, care managers acted as liaisons between pediatricians and a psychiatrist and provided education to parents. Just over a quarter of participants showed improvement of greater than one standard deviation on the Vanderbilt ADHD Diagnostic Parent Rating Scale, and just under one in seven on the Vanderbilt ADHD Diagnostic Teacher Rating Scale.

The remaining cohort had only 26 participants. It offered PCPs access to outpatient psychiatric consultations within three weeks. PCPs reported a high level of satisfaction with their improved skills in mental health care. There was no evaluation of the effect on symptoms.

With varied study designs, methodologies, and outcomes, the authors of the review could only conclude "that PCP collaboration with psychiatrists may be associated with the increased comfort level. However, the association with symptom outcome and increased capacity was variable." Given that randomized studies report only small effects, these shared care models cannot be routinely recommended.

July 22, 2021
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Are there Positive Aspects to ADHD?

Are there Positive Aspects to ADHD?

What are we to make of adults who exhibit the diagnostic criteria for ADHD, but are nevertheless high-functioning and successful? A trio of British investigators has just published six case studies that explore this question.  It would have been better for them to have conducted a much larger, controlled research study but, in the absence of such data in the area, these case studies are intriguing and may help guide more informative research.
The authors recruited six successful men between the ages of30 and 65 from a National Health Service tertiary service in London. Four were in long-term relationships, with children. All had good jobs.


In open-ended taped interviews of up to an hour in length, each was asked three questions:
1.     What do you think are the advantages and disadvantages of having ADHD?
2.     Please describe a time when you felt that your ADHD helped you to achieve something?
3.     What aspects of your ADHD would you miss if it went away?

Hyper-focus in ADHD is generally considered a deficit, inset-shifting, and task-switching. But the authors report that participants associated it with productivity. One said, "I think the energy that the ADHD brain seems to have....it's unfocused, quite scattered, chaotic and a bit random...but give that brain something that you can tune into, and it's your interest, then all that random stuff just goes boom... I get this incredible intense concentration and that's great for work."
Participants also saw advantages in divergent thinking, with one stating, "I'm an artist.... a creative type... a Bohemian.... you are most likely to be a creative person if you are a divergent thinker....and not convergent... I am very creative and that's through and through... I'm a fine art graduate, a musician, a published poet, an entrepreneur, a performer."
All the participants reported being seen as nonconformists. Depending on a viewpoint, that can be seen as either detrimental or advantageous.
Impulsivity is a core symptom of ADHD. Participants however related it to bravery, and more specifically adventurousness, spontaneity, and thrill-seeking. One said, "thrill-seeking is an ADHD thing... I can list in my life have done white water rafting, bungee jumping, hand-glider pilot ... I have done a lot in my life and achieved a lot and experienced a lot...... Furthermore, I would see a lot of that as being quite positive, and a lot of that is ADHD drive."
Another common theme was high energy and "spirit." One participant said, "I've got all this energy.... a lot of energy.... whatever it's to do with.... nature/nurture/spiritual stuff."
These testimonials are useful as a check on the usual narrative of impairment. ADHD does not predestine all it afflicts to an unfulfilling life. Many, often assisted by medication, still lead exciting, successful, rewarding lives.   Yet, we must be cautious in concluding that these individuals were successful because of their ADHD.  It is possible, even likely, that they had other strengths such as high intelligence that compensated for their ADHD symptoms.  We can not know from this report if their lives had been even more fulfilling or successful in the absence of ADHD.   See, for example, my blog about highly intelligent people with ADHD:  https://www.linkedin.com/pulse/20141126141502-65669938-smart-people-can-have-adhd-too/.
While the authors concede that "generalizing the findings of this study is not easy to do," they inexplicably "also argue that the positive aspects we found are relevant to other adults with ADHD regardless of sample size, age, gender or ethnicity."   It is not possible to draw such a definitive conclusion without a much larger sample.
On a hopeful note, they conclude, "This is a study that reaches out to people with lived experience of ADHD: service users, patients, family members, carers, partners, to say that not all symptoms of ADHD are maleficent. Recovery, high functionality, and flourishing with ADHD are possible. Too often people with lived experience hear about ADHD deficits, functional impairments, and associations with substance misuse, criminality, or other disadvantages on almost every level of life (school, work, relationships). ... This study affirms the positive human qualities, assets, and attributes in ADHD that can promote and sustain high functioning and flourishing."   I fully endorse the idea that those with ADHD can have wonderful lives, especially if they receive appropriate treatment, both medical and psychological.

July 20, 2021
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Immediate and Long-term Effects of Exercise on ADHD Symptoms and Cognition

Immediate and Longer-term Effects of Exercise on ADHD Symptoms and Cognition

A team of Spanish researchers has published a systematic review of 16 studies with a total of 728 participants exploring the effects of physical exercise on children and adolescents with ADHD. Fourteen studies were judged to be of high quality, and two of medium quality.

Seven studies looked at the acute effects of exercise on eight to twelve-year-old youths with ADHD. Acute means that the effects were measured immediately after periods of exercise lasting up to 30 minutes. Five studies used treadmills and two used stationary bicycles, for periods of five to 30 minutes. Three studies "showed a significant increase in the speed of reaction and precision of response after an intervention of 20-30 min, but at moderate intensity (50-75%)." Another study, however, found no improvement in mathematical problem-solving after 25 minutes using a stationary bicycle at low (40-50%) or moderate intensity (65-75%). The three others found improvements in executive functioning, planning, and organization in children after 20- to 30-minute exercise sessions.

Nine studies examined longer-term effects, following regular exercise over many weeks. One reported that twenty consecutive weekly yoga sessions improved attention. Another found that moderate to vigorous physical activity (MVPA) led to improved behavior beginning in the third week, and improved motor, emotional and attentional control, by the end of five weeks. A third study reported that eight weeks of starting the school day with 30 minutes of physical activity led to improvement in Connor's ADHD scores, oppositional scores, and response inhibition. Another study found that twelve weeks of aerobic activity led to declines in bad mood and inattention. Yet another reported that thrice-weekly 45-minute sessions of MVPA over ten weeks improved not only muscle strength and motor skills, but also attention, response inhibition, and information processing.

Two seventy-minute table tennis per week over twelve weeks improved executive functioning and planning, in addition to locomotor and object control skills.

Two studies found a significant increase in brain activity. One involved two hour-long sessions of rowing per week for eight weeks, the other three 90-minute land-based sessions per week for six weeks. Both studies measured higher activation of the right frontal and right temporal lobes in children, and lower theta/alpha ratios in male adolescents.

All 16 studies found positive effects on cognition. Five of the nine longer-term studies found positive effects on behavior. No study found any negative effects. The authors of the review concluded that physical activity "improves executive functions, increases attention, contributes to greater planning capacity and processing speed and working memory, improves the behavior of students with ADHD in the learning context, and consequently improves academic performance." Although the data are limited by a lack of appropriate controls, they suggest that, in addition to the well-known positive effects of physical activity, one may expect to see improvements in ADHD symptoms and associated features, especially for periods of sustained exercise.

July 18, 2021
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Omega-3 PUFAs and ADHD: Is there A Connection?

What do we know about the relationship between omega-3 PUFAs and ADHD?

There has been much interest in omega-3 Polyunsaturated fatty acids (PUFAs) as treatments for ADHD. Humans are unable to synthesize the omega-3 PUFA alpha-linolenic acid (ALA)and the omega-6 PUFA linoleic acid (LA), and must therefore obtain these through food, which is why they are known as essential fatty acids.  Because cells in the brain need omega-3 PUFAs, they have been studied as a treatment for ADHD by many researchers.  Several meta-analyses are available.

A 2014 meta-analysis by Elizabeth Haw key and Joel Niggcombined nine studies involving 586 participants. It found mean blood levels of omega-3 PUFAs in persons with ADHD to be lower than in controls. The standardized mean difference (SMD) effect size was medium (SMD = .42, 95% CI = .26-.59), with less than a one in one thousand probability of such a result being obtained by chance alone. Adjusting for publication bias reduced the effect size slightly to .36 with a 95% CI of .21-.51, in the small-to-medium range. The authors then examined whether omega-3 supplementation could help alleviate ADHD symptoms. Combining 16 studies with 1,408 participants, they found improvements, but this time with a small effect size (SMD = .26, 95% CI =.15-.37), again with less than a one in a thousand probability of such a result being observed by chance. Adjusting for publication bias reduced the effect size to .16 with a 95% CI of .03-.28.  For comparison, the SMD for stimulants is about 0.9.

Another meta-analysis conducted in the same year by BasantPuri and Julian Martins combined 18 PUFA supplementation studies involving1,640 participants. They also found a small effect size for reduced ADHD symptoms (SMD = .19, 95% CI = .09-.30, p<.001). Adjusting for publication bias further reduced the effect size to a paltry and statistically insignificant level (SMD = .12, 95% CI = -.01-.25). It should be noted that while16 of the studies involved omega-3 supplementation, two involved only omega-6supplementation. Yet the results for the latter did not differ noticeably from the former. When the authors limited the analysis to the 11 studies specifically including both the omega-6GLAand the omega-3 EPA, the effect size for reducing inattention symptoms was a bit higher(SMD = .31, 95% CI = .16-.46, p<.0001). But the results were not significantly different from those for the studies without the GLA+ALA combination (.012; 95% CI: .161-.137; p=.875). Publication bias was not addressed, and the hunt for a highly specific subset with positive results may have produced a false-positive finding.  The authors conceded, "Weaknesses of this study include the following: although the pooled effect was statistically significant, only two studies showed a significant effect by themselves; the funnel plot showed evidence of publication bias; there was evidence of reporting bias; few studies were formally registered; study methodological quality was variable, and the placebo used across studies varied."

A 2016 meta-analysis by Laura Lachance et al. tried looking for differences in the ratio of omega-6 to omega-3 PUFAs, and more specifically, AA to EPA, in the blood of persons with ADHD versus normally developing persons. Pooling five studies with485 participants, it found the omega-6 to omega-3 ratio to be significantly higher in persons with ADHD, and pooling three studies with 279 participants, it likewise found the AA to EPA ratio significantly higher.

A 2017 meta-analysis by Jane Pei-Chen Chang et al. Reexamined comparative levels of omega-3 PUFAs in ADHD patients versus normally developing controls. Combining six studies with 396 participants, ADHD patients had lower levels in blood and mouth tissue, with a medium effect size (SMD =.38) that was not statistically significant (p=.14).  Omega-6 levels were indistinguishable (SMD =.03) in the two groups. AA (SMD = .18, p=.33) and EPA (SMD = .25, p=.17) levels were slightly lower, but once again statistically not significant. DHA levels were lower as well, this time with a medium effect size (SMD = .56), but at the outer margin of significance (p=.05). Only by dropping one study were the authors able to claim significance for EPA, AA, and omega-3 differences.

Chang et al. also performed a meta-analysis of supplementation studies. Combining seven studies with 534 participants, they found a small to medium reduction in ADHD symptoms with omega-3 supplementation(SMD = .38, 95% CI = .2-.56, p<.0001). Corrections for publication bias were not reported. The authors also reported large reductions in both omission errors (SMD = 1.09, 95% CI = .43-.1.75, p<.001) and commission errors (SMD =2.14, 95% CI = 1.24-3.03, p<.00001) on a neuropsychological test of attention. But the former involved only 3 studies with 214 participants, and the latter only two studies with 85 participants.

Also in 2017, Pelsser et al. published a systematic review that identified only two meta-analyses of double-blind, placebo-controlled trials of PUFA supplementation. One of those, a 2012meta-analysis by Gillies et al., found no statistically significant declines in either parent-rated ADHD symptoms (five trials, 413 participants, SMD = -.17,95% CI = -.38-.03) or teacher-rated ADHD symptoms (four trials, 324participants, SMD = .05, 95% CI = -.18-.27). The other, a 2013 meta-analysis by Sonuga-Barke et al., found only a slight and barely statistically significant reduction in symptoms (11 trials, 827 participants, SMD = .16, 95% CI =.01-.31). Pelsser et al. concluded, "Considering the small average ESs [effect sizes] PUFA supplementation is unlikely to provide a tangible contribution to ADHD treatment."

Putting all of this together, there are indications that individuals with ADHD may have lower levels of omega-3 PUFAs, and that omega-3 supplementation may slightly reduce symptoms of ADHD, but the evidence remains inconclusive, with at best small effect sizes. It is possible, but not yet demonstrated, that omega-3 PUFAs might produce good outcomes in a small subset of patients.

July 16, 2021
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Is There a Relationship Between ADHD and Migraines?

Is there a relationship between ADHD and migraines?

A Danish team recruited 29,489 participants from voluntary blood donors between the ages of 17 and 67, ensuring a large sample size. Participants were asked to complete two simple questionnaires on digital tablets. One asked two questions: "Have you ever had a migraine?" and "Have you ever had visual disturbances lasting 5-60 min followed by a headache?" A yes to either was considered positive for migraine. The other used the ADHD Self-Report Scale, with 18 ADHD symptoms evaluated on a five-point scale.


Excluding those who did not answer all questions left 26,456 participants. The risk for migraines among those with ADHD was near twice the risk for others. The (odds)'s ratio (OR) was 1.8, with a 95 percent confidence interval from 1.53 to 2.12 (p < 0.001). The OR was higher among females (2.01) than males (1.64). For those with visual disturbances, the OR was higher (1.98) than for those without (1.52). The association disappeared in those over 60, with an OR essentially equal to one(0.98, 95% CI = 0.84 - 1.15, p = 0.8).


Although the authors concluded, "We demonstrate a significant comorbidity between migraine and ADHD in adults, and this is most prominent for participants with migraine with visual disturbances," the significance to which they refer is of the p-values, and should not be misinterpreted as an indication of a strong association, as the odds ratios point variably tweak, and weak-to-moderate associations, depending on subpopulations.  The work is, however, important as it points to another somatic comorbidity of ADHD. That list is growing and now includes obesity, eczema, and asthma.

July 14, 2021
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How Effective are Meditation-based Therapies for ADHD?

How effective are meditation-based therapies for ADHD?

An international team of researchers recently published a meta-analysis of randomized controlled trials examining the efficacy of meditation-based therapies. Thirteen randomized controlled clinical trials(RCTs) were included: seven, with 270 participants, focused on children and adolescents; the other six, with 339 participants, were on adults. Because only one of the RCTs was appropriately blinded, the results discussed below, although promising, must be considered preliminary.


Among children and adolescents, the meta-analysis revealed a significant, medium effect size (SMD = -0.44, 95% CI -0.69 to -0.19)on ADHD symptoms for meditation therapy versus no treatment. There were virtually no heterogeneity among studies and no sign of publication bias. Improvements in inattention and hyperactivity/impulsivity had similar effect sizes. Neuropsychological measures of inhibition and attention indicated small-to-medium effect sizes but failed to achieve statistical significance, perhaps due to the small numbers of trials and participants (159 and 179, respectively).


For adults, the significant effect size on ADHD symptoms was medium-to-large (SMD = -.66, 95% CI -1.21 to -0.11). Once again, there was little sign of publication bias. But in this case, there was great heterogeneity among the studies. Improvements in inattention and hyperactivity/impulsivity were again comparable, although they fell just short of statistical significance for the latter. Neuropsychological measures of the efficacy of medication therapy produced statistically significant medium effect sizes for inhibition (SMD = -0.54) and working memory (SMD = - 0.42), with virtually no heterogeneity or sign of publication bias.


Although these results are promising, the authors of the meta-analysis concluded, "Despite statistically significant effects on ADHD combined core symptoms, due to paucity of RCTs, heterogeneity across studies, and lack of studies at low risk of bias, there is insufficient methodologically sound evidence to support meditation-based therapies for ADHD."

July 12, 2021
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Is prenatal antidepressant exposure a risk factor for ADHD?

Is prenatal antidepressant exposure a risk factor for ADHD?

A systematic review of the literature found seven studies examining this question. Significantly, six were large cohort studies with a combined total of almost three million individuals. The other was a large case-control study with 7,874 participants.
The largest cohort study, with more than a million and a half children, found that prenatal antidepressant exposure increased the risk for ADHD.  The adjusted odds ratio was 1.6forany antidepressant and for selective serotonin reuptake inhibitors (SSRI). But sibling comparison models, which better adjust for confounds shared by siblings(e.g., poverty, stress in the home), this study found no increased risk of ADHD.
The second-largest cohort study, with over 875 thousand children, found a small adjusted risk of 1.2 for all antidepressants, with little variation by class of antidepressant. The fourth-largest study, with over 140 thousand children, likewise found a small adjusted risk of 1.2, which barely achieved statistical significance (95% CI 1.0-1.4).
The third-largest study, with over 190 thousand children, obtained an adjusted risk of 1.4 for all antidepressants. But it also pointed to a possible explanation for the small association found in this and other studies, suggesting that the apparent association with antidepressant use was due to ADHD's known genetic association with psychiatric conditions treated by antidepressants.
The fifth-largest study, with more than 55 thousand children, similarly found an adjusted risk of 1.7 for SSRIs and an adjusted risk of 1.7 for an unmediated maternal psychiatric disorder. Again, the underlying psychiatric disorder appears to be confounding the effect of antidepressants.
The sixth-largest study, with over 38 thousand children, found no evidence of any effect from SSRIs. Yet it found evidence of a large effect from bupropion, with an odds ratio of 3.6, and only one in 50 odds of obtaining such a result by chance (p = 0.02). However, it offered no comparison with untreated depression and made no adjustments for potential confounders.
The case-control study found an odds ratio of 2.3 for maternal use of any antidepressant, which dropped to a statistically non-significant 1.6 when adjusted for a maternal psychiatric disorder (95% CI0.66-3.71).

July 10, 2021
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High Dropout Rate in Six-Year Cohort Study of Medication Treatment for ADHD

High Dropout Rate in Six-Year Cohort Study of Medication Treatment for ADHD

Few studies have examined the safety and tolerability of ADHD medications (stimulants and atomoxetine) extending beyond six months, and none beyond a few years. A pair of Swedish neuroscientists at Uppsala University Hospital set out to explore longer-term outcomes. They conducted a six-year prospective study of 112 adults diagnosed with ADHD who were being treated with ADHD medications (primarily MPH, but also dexamphetamine and atomoxetine).


They found that at the end of that period, roughly half were still on medication, and half had discontinued treatment. There were no significant differences between the two groups in age, sex, ADHD severity, or comorbidity. The average ADHD score for the entire cohort declined to vary significantly, from a mean of 37 to a mean of 26, with less than one in a thousand odds of that being due to chance. There was also no sign of drug tolerance or a need to increase the dosage over time.
All 55 adults who discontinued treatment had taken MPH for at least part of the time. Eleven had also been treated with dexamphetamine(DEX) and 15 with atomoxetine (ATX). The average time on treatment was just under two years. Almost a third quit MPH because they perceived no beneficial effect. Since they were on average taking higher doses at discontinuation than initiation, that is unlikely to have been due to suboptimal dosage. Almost another third was discontinued for various adverse mental effects, including hyperactivity, elation, depressive moods, aggression, insomnia, fatigue, and lethargy. Another one in eleven quit when they lost contact with the prescribing physician. In the case of ATX, almost half quit because of what they perceived as adverse mental effects.


Among the 57 adults who remained on medication, four out of five reported a strong beneficial effect. Only two reported minimal or no effect. Compared with the group that discontinued, the group that remained on medication was far more likely to agree with the statements, "My quality of life has improved," and "My level of functioning has improved." Yet, as the authors caution, it is possible "that the subjects' subjective ratings contained a placebo-related mechanism in those who are compliant with the medication and pursue treatment over time." The authors reported that there were no significant differences in ADHD scores or ADHD severity between the group that quit and the group that remained on medication, even though, on average, the group that quit had been off medication for four years at follow-up.


We cannot explain why the patients who quit treatment showed similar levels of ADHD symptoms to those who continued treatment.  It is possible that some patients remit symptoms over time and do not require sustained treatment.  But we must keep in mind that there was a wide range of outcomes in both groups. Future work needs to find predictors of those who will do well after treatment withdrawal and those who do not.


Any decision on whether to maintain a course of medication should always weigh expected gains against adverse side effects. Short of hard evidence of continuing efficacy beyond two years, adverse events gain in relative importance. With that in mind, it is worth noting that this study reports that among those who remained on MPH, many reported side effects. More than a quarter complained of decreased appetite, one in four of dry mouth, one in five of anxiousness and increased heart rate, one in six of decreased sexual desire, one in nine of depressed mood, and one in eleven of insomnia.


This study breaks important ground in looking at the long-term effects of medication. It reaffirms findings elsewhere of the efficacy of ADHD medications. But contrary to the authors' conclusion, the data they present suggests the possibility that permanently medicating ADHD patients may not be more efficacious than discontinuation beyond a certain point, especially when balanced against adverse side effects.
But this is just one study with a relatively small sample size. This suggests a need for additional studies with larger sample sizes to pursue these questions with greater statistical reliability.

July 8, 2021
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ADHD and Adulthood Unhappiness

ADHD is Associated with Significantly Higher Probability of Unhappiness in Adults

An international team of researchers sets out to measure the association between ADHD symptoms and self-evaluations of happiness among adults in the general population of the U.K. A nationally representative sample of 7,274 adults was asked to rate their happiness on a three-point scale. They also used the Adult ADHD Self-Report Scale (ASRS) Screener to assess ADHD symptom levels.
Higher ADHD symptom levels were found to be inversely associated with self-assessments of happiness. Adults with the lowest ADHD symptoms (0-9 on theaters) were roughly twice as likely to report being happy as those scoring10-13, five times as happy as those scoring 14-17, and ten times as happy as those with the highest ADHD symptom scores (18-24). These results were highly significant.
That did not mean that most adults with high ADHD symptom scores were unhappy. Even among those with the highest ADHD symptom scores (18-24), a majority (58 percent) reported being either "fairly happy" or "very happy." Butonly11 a percent of that group reported being "very happy," as opposed to 44 percent of those scoring the lowest on ADHD symptoms.
While the association is clear and strong, establishing causation is trickier. As the authors acknowledge, "as the symptoms associated with ADHD are similar to, and sometimes overlap, with those that are commonly observed in individuals with other psychiatric disorders ... a screening instrument to identify ADHD symptoms may have had limited power to distinguish 'pure' ADHD and cases with ADHD symptoms related to other psychiatric disorders." Emotional instability and anxiety disorder each mediated more than a third of the association between ADHD and unhappiness, and depression almost a third. These could have been brought about by ADHD and could also have been produced by other psychiatric disorders.  Because the ASRS is not a diagnostic instrument, the authors concluded that "the results of this study should be considered provisional, until if, and when, they are replicated in those with a clinical diagnosis of ADHD with and without comorbid disorders."

July 6, 2021
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