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Noting that "despite a lack of solid evidence for their use, rTMS [repetitive transcranial magnetic stimulation]and tDCS [transcranial direct current stimulation] are already offered clinically and commercially in ADHD," and that a recent meta-analysis of ten tDCS studies found small but significant improvements in outcomes, but had several methodological shortcomings and did not include two studies reporting mostly null effects, a team of British neurologists performed a meta-analysis of all twelve sham-controlled, non-open-label, studies found in a comprehensive search of the peer-reviewed literature.
Ten of the twelve randomized-controlled trials used anodal stimulation of the dorsolateral prefrontal cortex, while the other two used anodal stimulation of the right inferior frontal cortex.
The trials explored several measures of cognition. The research team carried out a meta-analysis of all twelve trials, with a total of 232 participants, and found no significant improvement in attention scores from CDC, relative to sham stimulation. A second meta-analysis, of eleven trials with a total of 220 participants, assessed the efficacy of tDCS on improving inhibition scores, and again found no significant effect. A third meta-analysis, encompassing eight trials with a total of 124 participants, evaluated the efficacy of tDCS on improving processing speed scores, once again finding no significant effect.
The latter two meta-analyses approached the border of significance, prompting the authors to speculate that larger sample sizes could bring the results just over the threshold of significance. Even so, effect sizes would be small.
It is also possible that the trials focused on regions of the brain suboptimal for this objective, and thus the authors "cannot rule out the possibility that stimulation of other prefrontal regions (such as the right hemispheric inferior frontal cortex or dorsolateral prefrontal cortex or parietal regions), multiple session tDCS or tDCS in combination with cognitive training could improve clinically or cognitive functions in ADHD."
As to concerns about safety, on the other hand, "stimulation was well-tolerated overall."
The authors concluded that based on current evidence, tDCS of the dorsolateral prefrontal cortex cannot yet be recommended as an alternative Neurotherapy for ADHD.
Treating ADHD With Methylphenidate in Adults With Autism
A team from Harvard Medical School and Massachusetts General Hospital conducted a six-week open-label trial of liquid-formulation extended-release methylphenidate (MPH-ER) to treat ADHD in adults with high-functioning autism spectrum disorder (HF-ASD). ASD is a lifelong disorder with deficits in social communication and interaction and restricted, repetitive behaviors. Roughly half of those diagnosed with ASD also are diagnosed with ADHD.
This was the first stimulant trial in adults with both ASD and ADHD. There were twelve males and three female participants, all with moderate to severe ADHD, and in their twenties, with IQ scores of at least 85.
The use of a liquid formulation enabled doses to be raised very gradually, starting with a daily dose of 5 mg(1mL) and titrating up to 60 mg over the first three weeks, then maintaining that level through the sixth week. Participants were reevaluated for ADHD symptoms every week during the six-week trial. The severity of ASD was assessed at the start, midpoint, and conclusion of the trial, as were other psychiatric symptoms.
Before the trial, researchers agreed on a combination of targets on two clinician-rated scoring systems that would have to be reached for treatment to be considered successful. One is a score of 2 or less on the CGI-S, a measure of illness severity, with scores ranging from 1 (normal, not at all ill) to 7 (most extremely ill). The other is a reduction of at least 30 percent in the AIS RS score, which combines each of 18 symptoms of ADHD on a severity grid (0=not present; 3=severe; overall minimum score: 0; overall maximum score: 54).
After the trial, twelve of the fifteen patients (80 percent) met the preset conditions for success. Fully fourteen (93 percent) saw a ≥ 30 percent reduction in their AISRS score, while twelve scored ≤ 2 on illness severity.
However, when using the patient-rated ASRS scoring system, only five (33 percent) saw a ≥ 30 percent reduction in ADHD severity.
Thirteen participants (87percent) reported at least one adverse event, and nine (60 percent) reported two or more. One reported a serious adverse event (attempted suicide) in a patient with multiple prior attempts. Because the attempt was not deemed due to medication, they continued and completed the trial. Seven participants experienced titration-limiting adverse events (headaches, palpitations, jaw pain, and insomnia). Headache was most frequent (53%), followed by insomnia and anxiety(33% each), and decreased appetite (27%).
During the trial, weight significantly decreased, while pulse significantly increased. There were no significant differences in other vital and cardiovascular measurements.
The authors concluded, "this OLT of short-term MPH-ER therapy documents that acute treatment with MPH-ER in young adults with ASD was associated with significant improvement in ADHD symptoms, mirroring the typically-expected magnitude of response observed in adults with only ADHD. Treatment with MPH-ER was well-tolerated, though associated with a higher than expected frequency of adverse events."
They also cautioned, "The results of this study need to be considered in light of some methodological limitations. This was an open-label study; therefore, assessments were not blind to treatment. We did not employ a placebo control group and, therefore, cannot separate the effects of treatment from time or placebo effects. ... firmer conclusions regarding the safety and efficacy of MPH-ER for the treatment of ADHD in HF-ASD populations await results from larger, randomized, placebo-controlled clinical trials."
ADHD is far more prevalent among persons with AUD (roughly20 percent) than it is in the general population. The most accurate way of identifying ADHD is through structured clinical interviews. Given that this is not feasible in routine clinical settings, ADHD self-report scales offer a less reliable but much less resource-intensive alternative. Could the latter be calibrated in a way that would yield diagnoses that better correspond with the former?
A German team compared the outcomes of both methods on 404 adults undergoing residential treatment for AUD. All were abstinent while undergoing evaluations. First, to obtain reliable ADHD diagnoses, each underwent the Diagnostic Interview for ADHD in Adults, DIVA. If DIVA indicated probable ADHD, two expert clinicians conducted successive follow-up interviews. ADHD was only diagnosed when both experts concurred with the DIVA outcome.
Participants were then asked to use two adult ADHD self-report scales, the six-item Adult ADHD Self Report Scale v1.1 (ASRS) and the 30-item Conner's Adult ADHD Rating Scale (CAARS-S-SR). The outcomes were then compared with the expert interview diagnoses.
Using established cut-off values for the ASRS, less than two-thirds of patients known to have ADHD were scored as having ADHD by the test. In other words, there was a very high rate of false negatives. Lowering the cut-off to a sum score ≥ 11 resulted in an incorrect diagnosis of more than seven out of eight. But the rate of false positives shared to almost two in five. Similarly, the CAARS-S-SR had its greatest sensitivity (ability to accurately identify those with ADHD) at the lowest threshold of ≥ 60, but at a similarly high cost in false positives (more than a third).
The authors found it was impossible to come anywhere near the precision of the expert clinical interviews. Nevertheless, they judged the best compromise to be to use the lowest thresholds on both tests and then require positive determinations from both. That led to successfully diagnosing more than three out of four individuals known to have ADHD, with a false positive rate of just over one in five.
Using this combination of the two self-reporting questionnaires with lower thresholds, they suggest, could substantially reduce the under-diagnosis of ADHD in alcohol-dependent patients.
Autism spectrum disorder (ASD) is frequently comorbid with ADHD. Among adults with ADHD, as many as half are reported to also have ASD.
A Dutch team set out to answer two questions:
1) Do adults with ADHD and comorbid ASD experience less effectiveness in pharmacological treatment for ADHD than adults with only ADHD
2) Do adults with ADHD and comorbid ASD experience different or more severe side effects of pharmacological treatment for ADHD than adults with only ADHD, as measured in side effect scores, blood pressure, heart rate, and weight?
This was a retrospective study, using well-documented medical records, of the effects of drug treatment with methylphenidate (MPH), dexamphetamine (DEX), atomoxetine (ATX), bupropion, or modafinil.
The researchers compared 60 adults with comorbid ASD and ADHD to 226 adults with only ADHD. ADHD symptoms were scored using the Conner's ADHD Rating Scale: Self Report-Short Version (CAA RS: S-S). Side effects of ADHD medication were measured using either a 13-item or 20-item checklist with 4-point scales for item response. Researchers also tracked changes in body weight, blood pressure, and heart rate.
Following treatment, ADHD symptoms among the comorbid group declined by a quarter, and among the ADHD-only group by almost a third. There was no significant difference between men and women. Controlling for age, gender, and ADHD subtype, a comorbid diagnosis of ASD also did not significantly affect ADHD symptom reduction.
Turning to side effects, in the ADHD+ASD group, there were significant increases in decreased appetite and weight loss, and decreases in agitation, anxiety, and sadness/unhappiness. In the ADHD-only group, there were significant increases in decreased appetite, weight loss, and dry mouth, and decreases in sleeping disorder, nervousness, agitation, anxiety, and sadness/unhappiness. Yet there were no significant differences between the two groups. Side effects increased and decreased similarly in both. Likewise, there were no significant differences between the groups in changes in heart rate and blood pressure. The only significant difference in medication dosage was for bupropion, which was higher in the ADHD+ASD group, though without any sign of the difference in side effects.
The authors concluded that this retrospective study "showed pharmacological treatment of adults with diagnoses of ADHD and ASD to be just as successful as the pharmacological treatment of adults with only ADHD," but cautioned that "randomized controlled trial should be conducted to evaluate the effectiveness and possible side effects of pharmacological treatment for ADHD in patients with ASD more reliably."
In this study, researchers found subtle differences in the cortex of the brains of children with ADHD.
The ENIGMA-ADHD Working Group published a second large study on the brains of people with ADHD in the American Journal of Psychiatry this month. In this second study, the focus was on the cerebral cortex, which is the outer layer of the brain.
ADHD symptoms include inattention and/or hyperactivity and acting impulsively. The disorder affects more than one in twenty (5.3%) children, and two-thirds of those diagnosed continue to experience symptoms as adults.
In this study, researchers found subtle differences in the brain's cortex when they combined brain imaging data on almost 4,000 participants from 37 research groups worldwide. The differences were only significant for children and did not hold for adolescents or adults. The childhood effects were most prominent and widespread for the surface area of the cortex. More focal changes were found in the thickness of the cortex. All differences were subtle and detected only at a group level, and thus these brain images cannot be used to diagnose ADHD or guide its treatment.
These subtle differences in the brain's cortex were not limited to people with the clinical diagnosis of ADHD: they were also present - in a less marked form - in youth with some ADHD symptoms. This second finding results from a collaboration between the ENIGMA-ADHD Working Group and the Generation Study from Rotterdam, which has brain images of, 2700 children aged 9-11 years from the general population. The researchers found more symptoms of inattention to be associated with a decrease in cortical surface area. Furthermore, siblings of those with ADHD showed changes to their cortical surface area that resembled their affected sibling. This suggests that familial factors such as genetics or shared environment may play a role in brain cortical characteristics.
This is the largest study to date to look at the cortex of people with ADHD. It included 2246 people with a diagnosis of ADHD and 1713 people without, aged between 4 and 63 years old. This is the second study published by the ENIGMA-ADHD Working Group; the first examined structures that are deep in the brain. The ADHD Working Group is one of over 50 working groups of the ENIGMA Consortium, in which international researchers pull together to understand the brain alterations associated with different disorders and the role of genetic and environmental factors in those alterations.
The authors say the findings could help improve understanding of the disorder. 'We identify cortical differences that are consistently associated with ADHD, by combining data from many research groups internationally. We find that the differences extend beyond narrowly-defined clinical diagnoses and are seen, in a less marked manner, in those with some ADHD symptoms and unaffected siblings of people with ADHD. This finding supports the idea that the symptoms underlying ADHD may be a continuous trait in the population, which has already been reported by other behavioral and genetic studies.'. In the future, the ADHD Working Group hopes to look at additional key features in the brain - such as the structural connections between brain areas - and to increase the representation of adults affected by ADHD, on whom limited research has been performed to date.
A Spanish team of researchers recently completed a comprehensive review of studies looking for links between compulsive video gaming (both online and offline) and a variety of psychological disorders, including anxiety, depression, social phobia, and ADHD. The focus was on behavior "of sufficient severity to result in significant impairment in personal, family, social, educational, occupational or other important areas of functioning."
The team identified 24 studies, of which eight with a combined total of 16,786 participants looked for associations with either ADHD or its hyperactivity component. Participants included children, adolescents, and adults. One large longitudinal study, with 3,034 participants, found no association. Another study with 1,095 participants found a small effect. Two more, with a combined total of 11,868 found medium effect sizes. Four studies found large associations, but their combined total number of participants, was789, comprising less than a twentieth of the combined participants.
The authors concluded, "The relationship between Internet Gaming Disorder and ADHD and hyperactivity symptoms were analyzed in eight studies. Seven of them reported full association, with four finding large, two finding small, and one reporting moderate, effect sizes. The studies comprised two case-control, five cross-sectional and one longitudinal design; they later found no association between the two variables."[1]They also emphasized that 87 percent "of the studies describe significant correlations ... with ADHD or hyperactivity symptoms."[2]
Yet they did not note that all the studies with large effect sizes were comparatively small. And while they presented funnel charts evaluating publication bias for anxiety and depression, they did not do so for ADHD, where the small studies with very large effect sizes suggest publication bias (i.e., that evidence for association is exaggerated due to the early publication of positive findings).
Leaving out these small studies, the four high-powered studies with 15,997 participants reported effect sizes ranging from none to medium. Overall, that suggests that there is an association between ADHD and video gaming, though not a particularly strong one. Moreover, due to the nature of the study designs, this work cannot conclude that the small effect observed is due to playing video games being a risk factor for ADHD or to the possibility that ADHD youth are more attracted to video games than others.

A German team recruited 104 adults with ADHD at both inpatient and outpatient ADHD clinics, and from ADHD self-help groups. Just under two-thirds were being treated with ADHD drugs, most with methylphenidate.
Just under a quarter reported high internalized stigma. Two in five reported high levels of alienation, meaning a sense of "not being a fully functioning, valuable member of society." Three in ten reported high levels of social withdrawal.
On the other hand, only two participants reported high levels of stereotype endorsement, meaning personal acceptance of stereotypes associated with mental illness. And more than two-thirds reported high stigma resistance, meaning they were internally resistant to stigmatization. Thus, while most were free of significant internalized stigma, a still substantial minority were not.
Most of the participants expected to be discriminated against and treated unfairly by employers, colleagues at work, neighbors, and teachers should they reveal that they have ADHD. Relatively few expected to be discriminated against by health professionals, family, and friends. Almost half expected discrimination if they confided to strangers they were dating.
Over two-thirds of participants reported they had encountered public stereotypes concerning ADHD. But, on balance, they rated these at low levels of intensity. Nevertheless, among those perceiving such stereotypes, eight out of nine sensed some degree of public doubt about the validity of ADHD as a genuine ailment ("ADHD does not exist in adults"), and three out of four had at some point encountered the argument that "ADHD is invented by drug companies." More than four out of five had heard allegations that ADHD results from bad parenting, and almost three in four had heard the claim that it results from watching too much television or playing too many video games.
These data call for more education of the public about the nature and causes of ADHD. Information reduces stigmatization, so the widespread dissemination of the facts about ADHD is warranted.
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.
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.

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.
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."