What would you like to find today?

Noting that “The efficacy of surface electroencephalographic neurofeedback (EEG‐NF) for improving attentional performance assessed by laboratory measures in patients with attention‐deficit/hyperactivity disorder (ADHD) remains unclear,” a Taiwanese study team systematically searched seven databases, including the U.S. clinical trials database, for randomized controlled trials (RCTs) through January of 2022.

They identified fourteen RCTs with a combined 718 participants that met criteria for inclusion in meta-analysis. The net outcome was a small-to-medium effect size improvement in attentional performance for participants receiving EEG neurofeedback by contrast with “comparators.” 

The comparators varied widely: waitlist, treatment as usual, physical exercise, behavioral therapy, attention skills training, computer-aided attention training, medications, electromyographic biofeedback, sham EEG neurofeedback. This alone brings into question the meta-analysis outcome.

But there were additional methodological shortcomings. There was strong evidence of publication bias. And though the authors promised, “On encountering funnel plot asymmetry, potentially missing studies were imputed by using the Duval and Tweedie’s trim and fill method,” they never shared the outcome.

Another shortcoming was that only two of the fourteen RCTs blinded the participants, meaning that in twelve RCTs the participants were likely to be aware they were in the EEG neurofeedback group rather than the control group. And that made all the difference. The twelve unblinded RCTs were responsible for all the small-to-medium effect size improvement. There was no sign of improvement in the two blinded RCTs.

The authors tried to give a positive spin to these results, stating “our results supported the use of surface EEG-NF for improving attentional performance through the modulation of basic neurocognitive functioning in patients with ADHD,” while conceding, “However, given the small number of trials and the poor methodological qualities regarding blinding, our findings need to be judiciously interpreted and warrant further investigations for validation.”

A more candid assessment of this meta-analysis would be the one they began with: “The efficacy of surface electroencephalographic neurofeedback (EEG‐NF) for improving attentional performance assessed by laboratory measures in patients with attention‐deficit/hyperactivity disorder (ADHD) remains unclear.”

Virtual reality consists of computer-generated simulated environments. These can be on a flat screen as on a computer or tablet, in which the viewer’s peripheral vision is unimpaired. These types of virtual reality are non-immersive. Where vision of the outward actual environment is blocked, as by goggles, virtual reality becomes immersive.

A Romanian and British trio of researchers embarked on a systematic review and meta-analysis of randomized controlled trials (RCTs) to explore whether immersive virtual reality interventions are effective at improving cognitive deficits in children and adolescents with ADHD, what factors influence effect sizes, and whether such interventions are safe and likely to be adhered to by patients.

They distinguished between RCTs with passive control groups using either no treatment or waiting list, and RCTs using an active comparator group, where participants received an intervention with similar levels of contact with research personnel and a similar number of sessions as the intervention group (e.g., psychotherapy or non-immersive VR). Medication was also classified as an active comparator group.

A meta-analysis of seven RCTs with a combined 321 participants found that across all outcome measures, immersive virtual reality interventions were associated with large effect size improvements in cognitive functioning. Correcting for publication bias maintained the finding of large effect size improvements. Variation (heterogeneity) between studies was moderately high, but the mean outcome in every RCT was likewise positive though not always statistically significant.

A second meta-analysis of six RCTs totaling 273 persons likewise found large effect size improvements on attention measures. Again, heterogeneity was moderately high, but the mean outcome in every RCT was likewise positive though not always statistically significant.

There was no significant difference in outcomes between RCTs with active controls and those with passive controls. Nor did newer vs. older VR technology make any difference. Likewise, formal ADHD diagnosis vs. participants with ADHD-like symptoms but no formal diagnosis had no significant effect on outcomes.

The authors concluded, “immersive VR-based interventions are effective at improving global cognitive functioning, attention, and memory in children with ADHD compared with controls. Moreover, immersive VR is feasible in terms of treatment adherence and a safe cognitive rehabilitation tool.” 

But they noted, “Results should be cautiously interpreted given the poor quality of included studies and small sample.”

Children with disabilities are known to be at heightened risk of violence compared to their non-disabled peers. To what extent does this hold true for ADHD?

Denmark has a single-payer health insurance system through which health data about virtually the entire population can be cross-referenced with population, crime, welfare, and other registers through unique individual person numbers.

A Danish study team accessed national registers to examine the relationship between ADHD and criminal victimhood among nine yearly birth cohorts totaling more than 570,000 children and adolescents. 

Of these, 557,521, among them 12,040 with ADHD, were not reported as being exposed to violence, and 12,830, among which 1,179 with ADHD, were exposed to violence.

From the raw data, children and adolescents with ADHD were more than four times as likely to be exposed to violence than their typically developing peers.

The team then adjusted for other disabilities, family risk factors, gender, birth year, and ethnic background.

With these confounders out of the way, children and adolescents with ADHD remained more than twice as likely to be exposed to violence than their typically developing peers.

To place this outcome in further perspective:

• Brain injuries increased the odds of being exposed to violence by over 75% relative to typically developing peers.
• Physical and speech disabilities raised the odds by a bit over 35%.
• Intellectual and sensory disabilities, dyslexia, and congenital malformations had no effect. 
• Epilepsy reduced the odds of being exposed to violence by just under 20%, and autistic spectrum disorder by just over 25%.

Certain family risk factors further aggravated the odds:

• Violence in the family by more than 2.5-fold.
• Out-of-home care and breakup of parental relationship by more than 75%.

Perhaps surprisingly, substance abuse by family members had no effect whatsoever after adjusting for confounders.

Recognizing whether your ADHD is being managed appropriately requires an understanding of what constitutes effective treatment. Here are some indicators of proper ADHD treatment:

Comprehensive Evaluation: An appropriate diagnosis of ADHD involves a comprehensive evaluation, including medical history, clinical interviews, and assessment tools. It should also exclude other conditions that may mimic ADHD.

Clear Communication: Your doctor should provide a clear explanation of ADHD, its symptoms, treatment options, potential side effects, and expected outcomes. They should answer your questions patiently and help dispel any misconceptions.

Individualized Treatment Plan: ADHD treatment often involves a combination of medication, psychotherapy, and lifestyle changes. Your doctor should tailor the treatment plan to your specific needs, symptoms, and life circumstances.

Medication Management: If medication is part of your treatment plan, your doctor should monitor its effects and side effects closely, adjusting the dosage as necessary. Remember, the aim is to maximize benefits and minimize side effects.  Much research shows that it is usually best to start treatment with an FDA approved medication.  If your doctor decides otherwise, you should ask why.

Psychotherapy and Coaching: Pills don’t provide skills.  Many adults with ADHD never acquired life skills due to untreated ADHD. Cognitive-behavioral therapy (CBT) is beneficial for managing ADHD. Your doctor might recommend this and refer you to a psychologist, or they might provide some elements of these services themselves.  

Regular Follow-Ups: Regular follow-ups are critical to assess the effectiveness of the treatment plan and to make necessary adjustments. Your doctor should be tracking your progress and adapting your treatment as needed.

Empowering You: A good doctor will support you in managing your ADHD, providing education, resources, and tools that empower you to lead a healthy, fulfilling life.

Focus on Strengths: ADHD can come with strengths, such as creativity, dynamism, and the ability to think outside the box. An effective healthcare provider will help you leverage these strengths.

Involvement of Loved Ones: Depending on your circumstances, involving your loved ones in your treatment process can be beneficial. They can provide additional support and understanding.

Co-ordinating with Other Healthcare Providers: If you have other healthcare providers involved in your care, your doctor should communicate and coordinate with them to ensure consistent and comprehensive care.

Remember, you have the right to seek a second opinion if you feel your ADHD is not being appropriately managed. Trust your instincts and advocate for your health. It may also be helpful to join ADHD support groups (online or offline) to connect with others who share similar experiences. Their insights and recommendations could be beneficial.  Also keep in mind that achieving an optimal outcome for one’s ADHD often requires the doctor to try a few different medications as it is not currently possible to predict which patients do best on which medications.

Some animal studies and laboratory experiments have suggested that methylphenidate, the most widely prescribed pharmaceutical to treat ADHD, may weaken bones. On the other hand, other studies have indicated that methylphenidate is associated with lower risk of injury.

What, then, is the overall effect? 

The Hong Kong Hospital Authority is the sole public health provider for the city’s 7.3 million residents. Using the Clinical Data Analysis and Reporting System, the Authority’s electronic database, an international study team set out to explore this question.

Among 43,841 individuals with ADHD medication, the team identified 2,023 children and youths 5 through 24 years old with both methylphenidate prescription and a fracture between January 2001 and December 2020. 

In the six months following prescription, individuals were found to be roughly 40% less likely to be treated for a fracture than in the six months prior to prescription. The same held true when comparing the period 7 to 12 months after prescription with the six months prior to prescription. 

As a control, the team also looked at the effect of methylphenidate prescription on a completely unrelated condition – diseases of the esophagus, stomach, and duodenum. 

In this case, there was absolutely no difference in disease incidence for equal periods of time before and after initiation of methylphenidate treatment.

The team concluded, “for all-cause fractures, the results of the … within-individual comparison demonstrated that the use of methylphenidate is associated with lower risk … compared with the … period before the treatment initiation.”

Noting that “evidence on the association between ADHD and a physical condition associated with obesity, namely type 2 diabetes mellitus (T2D), is sparse and has not been meta-analysed yet,” a European study team performed a systematic search of the peer-reviewed medical literature followed by a meta-analysis, and then a nationwide population study.

Unlike type 1 diabetes, which is an auto-immune disease, type 2 diabetes is believed to be primarily related to lifestyle, associated with insufficient exercise, overconsumption of highly processed foods, and especially with large amounts of refined sugar. This leads to insulin resistance and excessively high blood glucose levels that damage the body and greatly lower life expectancy.

Because difficulty with impulse control is a symptom of ADHD, one might hypothesize that individuals with ADHD would be more likely to develop type-2 diabetes. 

The meta-analysis of four cohort studies encompassing more than 5.7 million persons of all ages spread over three continents (in the U.S., Taiwan, and Sweden) seemed to point in that direction. It found that individuals with ADHD had more than twice the odds of developing type 2 diabetes than normally developing peers. There was no sign of publication bias, but between-study variability (heterogeneity) was moderately high.

The nationwide population study of over 4.2 million Swedish adults came up with the same result when adjusting only for sex and birth year. 

Within the Swedish cohort there were 1.3 million families with at least two full siblings. Comparisons among siblings with and without ADHD again showed those with ADHD having more than twice the odds of developing type 2 diabetes. That indicated there was little in the way of familial confounding.

However, further adjusting for education, psychiatric comorbidity, and antipsychotic drugs dropped those higher odds among those with ADHD in the overall population to negligible (13% higher) and barely significant levels. 

The drops were particularly pronounced for psychiatric comorbidities, especially anxiety, depression, and substance use disorders, all of which had equal impacts.

The authors concluded, “This study revealed a significant association between ADHD and T2D [type 2 diabetes] that was largely due to psychiatric comorbidities, in particular SUD [substance use disorders], depression, and anxiety. Our findings suggest that clinicians need to be aware of the increased risk of developing T2D in individuals with ADHD and that psychiatric comorbidities may be the main driver of this association. Appropriate identification and treatment of these psychiatric comorbidities may reduce the risk for developing T2D in ADHD, together with efforts to intervene on other modifiable T2D risk factors (e.g., unhealthy lifestyle habits and use of antipsychotics, which are common in ADHD), and to devise individual programs to increase physical activity. Considering the significant economic burden of ADHD and T2D, a better understanding of this relationship is essential for targeted interventions or prevention programs with the potential for a positive impact on both public health and the lives of persons living with ADHD.”

Organophosphate pesticides were originally developed as nerve agents for chemical warfare, then used in lower doses as insecticides. 

Their neurotoxicity raises the possibility of effects on development of the nervous system at lower doses, including psychiatric disorders.

Previous studies have found mixed results for any association with ADHD.

Norway has a single-payer health insurance system that covers virtually the entire population, facilitating nationwide population studies. 

A primarily Norwegian study team used the Norwegian Mother, Father, and Child Cohort Study, a prospective population-based cohort that enrolled participants between 1999 and 2008 to explore possible associations. The study invited all 227,702 pregnant mothers to enroll, of which 112,908 (41%) actually enrolled.

Children were eligible for the present study if they were born after 2002, did not have Down’s syndrome or cerebral palsy, had available maternal biospecimens, were the result of a singleton pregnancy, and lived near Oslo (the location of the clinic). That left a sample of 24,035.

The team used the Norwegian Patient Registry (NPR) to identify diagnosed cases of ADHD. 

From the final eligible population, the team randomly selected 552 mother-child pairs to represent the exposure distribution in the population of pregnancies that gave rise to the cases of ADHD.

At about 17 weeks into pregnancy, maternal spot urine samples were collected at the mother’s first ultrasound appointment. These samples were then tested for concentrations of organophosphate metabolites (breakdown chemicals). 

Adjustments were made for a variety of possible confounding variables: season, birth year, maternal education, vegetable intake, fruit intake, maternal self-reported ADHD, financial status, other organophosphorus pesticides, and sex.

Comparing higher versus lower maternal exposures to organophosphates, no significant differences emerged in rates of ADHD diagnosis among offspring.

Unprescribed amphetamines are the second most commonly used illicit drugs worldwide. Persons with methamphetamine or amphetamine use disorders (MAUD) have elevated rates of mortality, primarily from acute poisoning, but also from suicide, homicide, cardiovascular disease, and injuries. Illicit amphetamine use is also associated with aggressive behavior and criminality.

There are presently no approved pharmacological interventions for treating MAUD. 

A Finnish study team used the Swedish national registers to explore relationships between various drug treatments, including ADHD medications, and hard outcomes – hospitalization and death – among persons with MAUD.

The team looked at all Swedish residents aged 16 to 64 years with a registered first-time treatment contact due to MAUD between July 1, 2006 and December 31, 2018. They matched this cohort with data from the Prescribed Drug Register from July 2005 to December 2018.

They adjusted for the following confounding variables: age, sex, education, granted disability pension, long-term sickness absence during previous year (more than 90 days), and medication-related comorbidities.

The cohort consisted of 13,965 persons diagnosed with MAUD. Of these, 11,492 (about three out of four) were either hospitalized (10,341) or died (1,151) in the follow-up period.

The study looked at a variety of prescription drugs, including six ADHD medications: methylphenidate, atomoxetine, modafinil, amphetamine, dexamphetamine, and lisdexamphetamine. Prescriptions for none of these were significantly associated with higher risk of hospitalization or death from substance used disorder.

On the other hand, persons diagnosed with MAUD but prescribed lisdexamphetamine were in all instances at significantly lower risk. Lisdexamphetamine users were 18% less likely to be hospitalized for substance use disorder in within-individual and 25% less likely to be hospitalized in between-individual analyses. Lisdexamphetamine users also had half the risk of all-cause mortality. 

The authors concluded, “In this Swedish nationwide cohort study, use of lisdexamphetamine was consistently associated with a reduction in risk of death and hospitalization in persons with amphetamine or methamphetamine. Use of antidepressants were associated with an increase in risk of hospitalization due to SUD and any hospitalization or death. Benzodiazepine use was associated with poor outcomes.”

Thanks to improvements in cancer treatment, there is a growing population of childhood and adolescent cancer survivors (CACSs). CACSs are at an increased risk of chronic physical, psychological, and social problems because of their cancer experiences and intensive cancer treatments. These include depression, anxiety, suicidal ideation, and post-traumatic stress disorder (PTSD). 

To what extent, if at all, does this also apply to ADHD? Noting that “previous studies … have reported inconsistent findings,” a local research team took advantage of Taiwan’s mandatory single-payer National Health Insurance that covers over 99% of the island’s population. More specifically, the National Health Insurance Research Database (NHIRD) maintains data on the insured population available on formal request for study purposes.

Linking the catastrophic illness database, mental disorders database, and longitudinal health insurance database, they tracked children age younger than 10 years and adolescents aged 11-17 years who were diagnosed with any malignancy (cancer) between 2002 and 2011 with no history of major psychiatric disorders (including ADHD). Parental history of major psychiatric disorders was likewise controlled as a potential confounder.

The team identified 5,121 CACSs, which they matched one to ten with 51,210 age-, sex-, income-, and residence-matched cancer-free controls.

ADHD diagnoses were made by board-certified psychiatrists during the study follow-up period (from enrollment through 2011) based on a comprehensive clinical interview and clinical judgment. 

Cancer survivors were diagnosed with ADHD at more than six times the rate of matched controls. Survival duration made no significant difference in this outcome. 

Cancers of bone, connective tissue, skin, and breast were associated with a more than threefold increase in risk of an ADHD diagnosis. For cancers of the circulatory system, there was a more than sixfold increased risk of ADHD, and for those of the genitourinary organs, more than sevenfold increased risk. 

For brain cancer survivors, the increased risk of ADHD was more than twelvefold. That may be at least in part because the brain itself was targeted for treatment in these instances, which plausibly could cause damage resulting in psychiatric disorders.

The team concluded, “we observed a comparatively higher risk of MPDs [major psychiatric disorders] among CACSs than among controls and likewise found that such risks varied across different cancer types. Survivors of both CNS [central nervous system] and non-CNS cancers have increased risks of MPD diagnoses. Among the enrolled CACSs, ASD [autism spectrum disorder] and ADHD were associated with most types/categories of cancers. Long-term care of this vulnerable population must include psychosocial interventions for patients and their families. Physicians need to be aware of early signs of mental health problems in this high-risk subpopulation and arrange early interventions accordingly.”

A Chinese study team has performed an updated meta-analysis of randomized clinical trials (RCTs) published through July 2022, looking specifically at the effects of chronic exercise on ADHD core symptoms and executive functions in children and adolescents.

The researchers defined chronic to mean exercise interventions lasting at least six weeks, with the longest clocking in at well over a year (72 weeks). 

They only included RCTs with blinding of all assessors who measured the primary outcomes, to guard against any conscious or unconscious bias.

A total of 22 studies met criteria for inclusion in the series of meta-analyses they performed. The RCTs were widely distributed, with four from North America, three from Africa, three from Europe, eleven from Asia, and one from Oceania.

Three studies were rated as being at low risk of bias, the other 19 at moderate risk of bias.

Meta-analysis of eleven RCTs with a combined 514 participants reported a small-to-medium reduction in ADHD core symptoms. Between-study variation (heterogeneity) was moderate, and there was no indication of publication bias.

Breaking that down by age group, for children (eight RCTs, 357 children) the reduction in core symptoms was likewise small-to-medium, versus a medium effect size reduction among adolescents (three RCTs, 157 adolescents), with no heterogeneity.

When the control group received no treatment or was sedentary (8 RCTs, 422 participants), the effect size remained small-to-medium, whereas when the control group received education, it became large (two RCTs, 58 participants). 

Improvements in executive functions were even more pronounced. Meta-analysis of 17 RCTs with a combined 795 participants yielded a medium-to-large effect size reduction in executive functions overall. Heterogeneity was moderate, with absolutely no sign of publication bias.

More specifically, there was a medium effect size improvement in working memory (10 RCTs, 290 participants), a medium-to-large effect size improvement in cognitive flexibility (8 RCTs, 206 participants), and a large effect size improvement in inhibition (12 RCTs, 299 participants). 

Once again, adolescents benefited more than children. Whereas children showed medium effect size improvements in executive function (14 RCTs, 659 children), adolescents registered enormous improvements (3 RCTs, 136 adolescents).

One note of caution, though. Among RCTs rated low risk of bias, effect size improvements in both ADHD core symptoms (3 RCTs, 180 participants) and executive functions (2 RCTs, 86 participants) were small and did not reach statistical significance. That suggests a need for more and better RCTs to reach a more settled verdict.

For now, the authors concluded, “This meta-analysis suggests that CEIs [chronic exercise interventions] have small-to-moderate effects on overall core symptoms and executive functions in children and adolescents with ADHD.”