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Now that ADHD pharmaceuticals are among the most widely prescribed medications during pregnancy, we need to be aware of any long-term harms to offspring from in-utero exposure.

Denmark has a single-payer public health care system that encompasses virtually its entire population. Combined with national registers that track demographic as well as health data for the whole population, this makes it easy to do population-wide studies.

Availing itself of these registers, an international study team looked at all 1,068,073 single births from 1998 to 2015. It then followed all these individuals through the end of 2018, or until any developmental diagnosis, death, or emigration, whichever came first.

The team compared children of mothers who continued ADHD medication (methylphenidate, amphetamine, dexamphetamine, lisdexamphetamine, modafinil, atomoxetine, clonidine) during pregnancy with children of mothers who discontinued ADHD medication before pregnancy. There were 898 of the former and 1,270 of the latter in the cohort.

To reduce the influence of potential confounding variables, the team adjusted for maternal age, parity, maternal psychiatric history, in- or outpatient admission to psychiatric ward within two years prior to pregnancy and until delivery, use of other psychotropic medications during pregnancy, number of hospitalizations during pregnancy not related to psychiatry, smoking during pregnancy, living alone, education, birthyear, and psychiatric history of the father. 

Children exposed in utero to ADHD medication were found to be at no greater risk of any developmental impairment.

The timing of the exposure by trimester of pregnancy made no difference. Neither did the duration of exposure.

Neither children exposed to stimulant medications (methylphenidate, amphetamine, dexamphetamine, lisdexamphetamine, modafinil) nor to non-stimulants (atomoxetine, clonidine) were at greater risk of any developmental impairment. 

Focusing more narrowly on specific impairments, children exposed in utero to ADHD medication were no more likely to be autistic. They were more likely to have ADHD, but the association did not reach statistical significance.

Children exposed in utero to ADHD medication were also no more likely to develop hearing or cerebral vision impairment or febrile seizures or a growth impairment. Surprisingly, they were 40% less likely to become epileptic, the only statistically significant association found in the study.

The authors concluded, “Our results are important because stimulant medications are critical for many adults, including women of childbearing age, to perform their essential functions at work, home, and school. Pregnant women who depend on stimulants for daily functioning must weigh the potential of exposing their fetus to unknown developmental risks against potential medical, financial, and other consequences to both mother and child that are associated with exacerbation of ADHD symptoms when stopping the medication, such as inability to maintain employment and unsafe driving. The present study provides reassurance that several essential categories of child outcomes that could reasonably be suspected to be affected by stimulants, including body growth, neurodevelopment, and seizure risk, do not differ based on antenatal stimulant exposure. Future studies would benefit from larger sample sizes making it possible to conduct stratified analyses on ADHD medication type.”

Monitoring the Future is a multicohort U.S. national longitudinal study of adolescents followed up into young adulthood. 

The U.S. research team used data from this study to follow 5,034 twelfth graders over a period of six years, until they were 23 and 24 years of age.

Prescription stimulant misuse was assessed at baseline and each follow-up survey year by asking how often they used prescription stimulants without a physician’s orders. They were similarly asked about cocaine and methamphetamine use.

The study team adjusted for the following confounding variables: sex, race and ethnicity, parents’ level of education, urbanicity, U.S. region, cohort year, grade point average during high school, past-30-day cigarette use (at 18 years of age), past-2-week binge drinking (at 18), past-year marijuana use (at 18), past-year prescription opioid misuse (at 18), past-year prescription stimulant misuse (at 18), lifetime cocaine use (at 18), lifetime methamphetamine use (at 18), lifetime use of nonstimulant therapy for ADHD (at 18), and discontinued use of stimulant therapy for ADHD (at 18).

With these adjustments, they found that stimulant use for ADHD was in no way associated with subsequent cocaine use. In fact, it was associated with lesser odds of subsequent cocaine use, though the association was not statistically significant.

Likewise, they reported that stimulant use for ADHD was in no way associated with subsequent methamphetamine use.

On the other hand, those who used prescription stimulants without a physician’s orders were 2.6 times more likely to subsequently use either cocaine or methamphetamine.

The team concluded, “In this multicohort study of adolescents exposed to prescription stimulants, adolescents who used stimulant therapy for ADHD did not differ from population controls in initiation of illicit stimulant (cocaine or methamphetamine) use, which suggested a potential protective effect, given evidence of elevated illicit stimulant use among those with ADHD. In contrast, monitoring adolescents for PSM is warranted because this behavior offered a strong signal for transitioning to later cocaine or methamphetamine initiation and use during young adulthood.”

Noting that “little is known about whether school-level stimulant therapy for ADHD is associated with NUPS [nonmedical use of prescription stimulants] among US secondary school students,” a team of American researchers searched for answers in a nationally representative sample of 3,284 U.S. secondary schools with well over 150,000 high school students.

“Previous studies,” the authors continued, “have largely neglected school-level factors associated with NUPS among US secondary school students, including school size, school geographical location, school-level racial composition, school-level rates of substance use (eg, binge drinking), and school-level stimulant therapy for ADHD.”

In surveys, students were asked if they had ever taken stimulant medications for ADHD under a physician’s or health professional’s supervision, with three possible answers: no, yes but only in the past, and yes, currently. Responses for use in the past, and separately for current use, were combined and aggregated to the school level to reflect the percentage of the study body who used prescription stimulants for ADHD. 

The surveys explored NUPS by asking, “On how many occasions (if any) have you taken amphetamines or other prescription stimulant drugs on your own—that is, without a doctor telling you to take them... in your lifetime?...during the last 12 months?...during the last 30 days?” 

The study team controlled for sex, race and ethnicity, parental education, GPA, binge drinking, cigarette smoking, cannabis use, cohort year, school type, grade level, urbanicity, school size, US Census region, % of student body with low grades, % female, % with at least one parent with a college degree, % White, % binge drinking during past 2 weeks, % cigarette smoking in past 30 days, and % cannabis use during the past 30 days. The analysis also included individual-level medical use of stimulant therapy for ADHD history to estimate individual-level past-year NUPS. Finally, it included both individual-level and school-level risk factors to assess individual-level past-year NUPS.

With all these adjustments, at the individual level, both high school students presently on prescribed stimulant therapy for ADHD and those who had previously been on such prescribed therapy were more than twice as likely to engage in past-year NUPS as those who were never on prescribed stimulant medication.

Turning to the school level, in schools where 12% or more of students were on prescribed stimulant therapy for ADHD, students in general were 36% more likely to engage in past-year NUPS than in schools where none of the students were on prescribed stimulant therapy for ADHD.

This is not surprising, as it confirms that students who use prescription drugs for nonmedical often get their supply from fellow students who are prescribed those drugs.

While at the individual level, binge drinking, cigarette smoking, and cannabis use were strong predictors of NUPS, at the whole-school level they had no significant effect. A poor grade point average mildly increased risk in the individual, but high percentages of students with low grades had no effect on peer NUPS. Race and ethnicity made a difference at the individual level (NUPS significantly more likely among White students than Blacks and Hispanics), but made no difference at the school level.

The team concluded, “These findings suggest that school-level stimulant therapy for ADHD and other school-level risk factors were significantly associated with NUPS and should be accounted for in risk-reduction strategies and prevention efforts.”

In our digital age, the internet serves as a powerful platform for accessing health information. Yet, with this great power comes great responsibility. Misinformation, particularly concerning ADHD (Attention-Deficit/Hyperactivity Disorder), is rife online, leading to confusion, the perpetuation of stigma, and potentially harmful consequences for those affected by the disorder and their loved ones. This blog will delve into some of these misconceptions, their impacts, and how to ensure the ADHD information you come across online is reliable, with a special emphasis on a recent study examining ADHD content on TikTok.

The Misinformation Problem

ADHD is a neurodevelopmental disorder that affects both children and adults. It's characterized by patterns of inattention, impulsivity, and hyperactivity that are persistent. Despite its recognition as a well-documented medical condition, it is often misunderstood, partly due to widespread misinformation.

Common ADHD misconceptions include:

ADHD is not a real disorder: This belief is found scattered across online forums, and even some ill-informed news articles.

ADHD is a result of bad parenting: Numerous online discussions blame parents for their child's ADHD. However, research has shown that ADHD has biological origins and is not a result of parenting styles.

ADHD only affects children: Many websites and social media posts promote this myth, but ADHD can continue into adulthood.

ADHD medication leads to substance abuse: Certain posts on social media may wrongly claim that ADHD medication leads to substance abuse.

A recent study explored the quality of ADHD content on TikTok, a popular video-sharing social media platform. Researchers investigated the top 100 most popular ADHD-related videos on the platform. Shockingly, they found that 52% of these videos were classified as misleading, while only 21% were categorized as useful. The majority of these misleading videos were uploaded by non-healthcare providers.

The Impact of Misinformation

Misinformation about ADHD can have harmful impacts on individuals with the disorder and their families:

Delayed diagnosis and treatment: Misinformation can deter individuals and parents from seeking professional help, leading to delays in diagnosis and treatment.

Increased stigma: False information can amplify societal stigma about ADHD, leading to misunderstanding and discrimination.

Harmful treatment approaches: Misinformation can lead individuals to opt for ineffective or even harmful treatments.

The proliferation of misleading ADHD content on platforms like TikTok only amplifies these problems. The TikTok study found that while the videos were generally understandable, they had low actionability — meaning they offered little practical advice for managing ADHD.

Identifying Reliable Information

Given the prevalence of misinformation, it's crucial to be able to distinguish between reliable and unreliable information about ADHD. Here are some pointers:

Use reputable sources: Trustworthy information often comes from recognized health organizations, government health departments, or reputable medical institutions.  Some examples are NIH, Mayo Clinic, CDC and www.ADHDevidence.org. 

Be wary of fake experts: If you see info from a self-proclaimed expert, you can check to see if they are really an expert by going to www.expertscape.com.  Or go to www.pubmed.gov to see if they’ve ever written anything about ADHD that has been approved by their peers.

Look for citations: Reliable sources often cite scientific research to back their claims.

Beware of sensational headlines: Clickbait headlines often oversimplify complex topics like ADHD.

Consult a professional: If you're unsure about any information, consult a healthcare professional.

The TikTok study's findings underscore the importance of these guidelines, as healthcare providers tended to upload higher quality and more useful videos compared to non-healthcare providers.

In our era of digital information, the challenge of separating ADHD facts from fiction is significant but not insurmountable. By becoming discerning consumers of online information, we can help prevent the spread of misinformation, support those affected by ADHD, and foster a more informed and understanding society. It's also essential for clinicians to be aware of the extent of health misinformation online and its potential impact on patient care. This way, they can guide their patients toward reliable sources and away from misleading content.

There is increasing interest in digital interventions to treat ADHD symptoms and to overcome deficits in executive functioning that are associated with this disorder. Executive functions such as working memory and cognitive speed originate in the frontal lobes of the brain, and guide voluntary goal-directed behavior. They affect reading speed and accuracy, reading comprehension, attention, and impulse control, among other behaviors important to the ability to function in social, educational, and professional environments.

A Swedish study team based at Umeå University recently conducted a systematic search of the medical literature to explore the efficacy of computerized cognitive training (CCT) to improve executive functioning in adults with ADHD.

They included published randomized controlled trials (RCTs) involving adults 18 to 65 years old with a primary diagnosis of ADHD. The controls were participants with either a passive (wait-list) or active (modified simple training) intervention.

Nine RCTs with a combined total of 285 participants met inclusion criteria. Lumping together all cognitive outcome types, meta-analysis reported a small effect size improvement that was just barely statistically significant (p = .048, with p < .05 as the boundary).

However, when separated out by individual outcome types – executive functioning, cognitive speed, general short-term memory, or ADHD symptom severity – the meta-analyses found no improvements that reached statistical significance. 

Moreover, all RCTs except one were judged as high risk of bias.

While it is possible that additional studies enlarging the pool of participants could lead to statistical significance, all effect sizes were small to begin with, which is not encouraging.

The team concluded, “Considering the small positive effect in this meta-analysis for overall cognitive outcomes, together with the lack of evidence for far transfer, practitioners and individuals with ADHD should weigh the costs (resources and time) against the benefits of training.”

A South Korean study team recently concluded the first RCT-only meta-analysis of game-based digital therapeutics (DTx).

Combining 14 RCTs with a total of 1,183 participants, they found a small effect size improvement in parent-rated attention symptoms for game-based DTx interventions over controls. Nine RCTs combining 424 participants likewise found a small effect size improvement in teacher-rated attention symptoms. Between-study variation (heterogeneity) was negligible, and there was no indication of publication bias.

Combining five RCTs with a total of 256 participants, they reported small effect size improvements in both parent and teacher-rated hyperactivity/impulsivity symptoms. But they found no improvement in hyperactivity symptoms alone, whether evaluated by parents or teachers. Heterogeneity was in all instances negligible, with no sign of publication bias. 

The team then compared game-based DTx interventions with pharmaceutical treatment. 

ADHD medications outperformed game-based DTx interventions for improvement of attention symptoms in both parent (four RCTs with a total of 128 participants) and teacher (three RCTs with 92 participants) ratings, with small-to-medium effect sizes. Medications likewise prevailed in improving hyperactivity/impulsivity symptoms, whether rated by parents or teachers, with small-to-medium effect sizes.

The team concluded, “This study is the first direct and indirect meta-analysis to compare the efficacy of game-based DTx between control and medication according to the assessor in an RCT. In conclusion, game-based DTx had a more significant effect than the control. Additionally, between medication treatment versus DTx, medication was more effective.”

An international study team has just reported findings from a series of meta-analyses exploring associations between ADHD medications and headaches in children and adolescents. 

First, to compare headache occurrence in individuals with ADHD to those without ADHD, the team performed a very large meta-analysis of twelve studies with over 2.7 million children and adolescents. Those with ADHD had twice the rate of headaches. 

There was no indication of publication bias, but there was considerable variation (heterogeneity) among studies, with crude odds ratios spanning from 0.9 to 3.37. Nevertheless, ten of the twelve studies pointed to higher odds among children and adolescents with ADHD. The four studies that controlled for age, sex, race, and other socioeconomic status variables reaffirmed the finding of a doubling of headache risk, this time with acceptable heterogeneity.

Three studies with a combined 7,755 participants found no difference in tension headaches, but five studies with over a quarter million persons found more than a doubling of the rate of migraine in children and adolescents with ADHD.

Next, the team performed meta-analyses of 58 randomized controlled trials (RCTs) of specific ADHD medications that met eligibility criteria for their systematic review. Because only a single eligible RCT apiece looked at bupropion and clonidine, these ADHD medications could not be included in the meta-analyses.

A meta-analysis of ten RCTs with a total of 2,672 participants found absolutely no association between use of amphetamines (including lisdexamphetamine) and headaches. Variation (heterogeneity) between studies was minimal, and there was no sign of publication bias.

A smaller meta-analysis of six RCTs with a combined 818 participants found a 24% increase in headaches among modafinil users, but it was not statistically significant, perhaps because of the much smaller combined sample size.

A meta-analysis of 17 RCTs with a total of 3,371 participants found a 33% increase in headache occurrence among methylphenidate users over placebo. Between-study variation (heterogeneity) was negligible, and there was absolutely no sign of publication bias. 

Similarly, a meta-analysis of 22 RCTs with a combined 3,857 participants reported a 29% increase in headache occurrence among atomoxetine users over placebo. Again, heterogeneity between studies was negligible, with absolutely no indication of publication bias.

Finally, a meta-analysis of eight RCTs with 1,956 participants found a 43% increase in headache occurrence among guanfacine users over placebo. Once again, with negligible heterogeneity and no indication of publication bias.

ADHD is associated with impaired executive functioning. Executive functions are a set of mental skills that include working memory, flexible thinking, and self-control. These are skills we use every day to learn, work, and manage daily life. Trouble with executive function can make it hard to focus, follow directions, and handle emotions. 

A Chinese study team searched for studies on non-pharmacological treatments of children and adolescents with ADHD aged 5 to 18 years intended to improve their executive functioning. 

An initial methodological weakness was the decision to combine studies using formal ADHD diagnoses based on professional psychiatric manuals (DSM 3/4/5 and ICD 10/11) and studies relying on other methods such as parent reports.

This lack of rigor in identifying ADHD is surprising given that the team used studies that directly measured executive functioning through neurocognitive tasks, excluding those that relied on parent- or teacher-reported questionnaires. 

67 studies involving 74 training interventions met the criteria. Meta-analysis of all these studies, encompassing a total of 3,101 participants, suggested medium-to-large effect size improvements in executive functioning. There was evidence of publication bias, but trim-and-fill adjustment increased the estimated effect size to large.

Nevertheless, there were further methodological shortcomings:

• The meta-analysis mixed studies of substantially different interventions: cognitive training, executive function-specific curriculum, game-based training, neurofeedback, mindfulness, and physical exercise.
• There was tremendous variation (heterogeneity) between study outcomes. Such inconsistency casts doubt on the outcome unless subgroup analysis can explain it. 

In this case, subgroup analysis mostly failed to explain the heterogeneity, with a single exception. Meta-analysis of the 16 studies with 744 participants that explored executive function-specific curriculum found small-to-medium effect size improvements, with no heterogeneity. 

Unfortunately, the team did not perform a separate publication bias analysis on this subgroup, just as it failed to do so on any of the other subgroups.

By far the strongest evidence of benefit came from meta-analysis of the 17 studies with 558 participants evaluating physical exercise. Here the outcome pointed to very large effect size improvements in executive functioning. Yet once again, heterogeneity was extremely high. Breaking this down further between aerobic exercise and cognitively engaged physical exercise made no difference. Both types had the same very high effect size, with very wide heterogeneity. Again, there was no separate evaluation of publication bias on this group.

Meta-analyses of thirteen studies of neurofeedback combining 444 participants, and fifteen studies of cognitive training encompassing 727 participants, both pointed to just-short-of-large effect size improvements in executive function. Meta-analysis of twelve studies of game-based training with 598 participants indicated medium effect size gains. But again, in all three subgroups there was great variation between studies, and no analysis of publication bias.

While these meta-analyses are suggestive of efficacy, especially for physical exercise interventions, their methodological shortcomings mean we will have to await more rigorous meta-analyses to draw any more settled conclusions. Moreover, these meta-analyses did not evaluate the adequacy of the control groups used in the trials, which is a big shortcoming given prior work showing that the effect of non-pharmacologic treatments are very weak or non-existent when adequate controls are used.

During the COVID-19 pandemic, there were concerns about its disproportionate impact on children with ADHD. Canadian researchers decided to investigate whether symptoms of ADHD—such as inattention, hyperactivity, and impulsivity—had changed over the past three years due to the pandemic.

Research Approach

To explore this question, the researchers conducted a systematic review of peer-reviewed medical literature. They looked for studies that included children and adolescents aged three to eighteen and met the following criteria:

1. Reported ADHD symptoms at least once before the pandemic started (before March 2020) or provided a retroactive report of pre-pandemic symptoms.
2. Reported ADHD symptoms at least once after the pandemic began.

They found 18 studies with a total of 6,491 participants that could be combined for a meta-analysis. These studies were from four continents (North and South America, Asia, Europe) and ten countries (China, Japan, United States, Canada, Brazil, U.K., Germany, Spain, Italy, Lithuania).

Study Quality and Criteria

The researchers assessed the quality of the studies based on three criteria:

1. Clear description of the research setting.
2. Detailed description of data collection procedures.
3. Statistical assessment of the reliability and validity of measurement tools.

Ten studies met all three criteria, and the remaining eight met two out of three.

Findings

The meta-analysis revealed a small but statistically significant increase in ADHD symptoms after the onset of the pandemic. However, there was a high degree of variability (heterogeneity) in the results between studies. The researchers couldn't identify any reasons for this variability. Factors such as gender, age, study design (prospective vs. retrospective), and the identity of the symptom evaluator (self or caregiver) didn't significantly affect the results. Additionally, the researchers did not report any specific outcomes based on the ten higher-quality studies alone.

Moreover, there was strong evidence of publication bias. The researchers did not perform a trim-and-fill analysis, which could have shown how publication bias might have influenced the effect size. Given the small effect size initially reported, this leaves the overall findings uncertain.

Conclusion

While the study found a slight increase in ADHD symptoms among children during the pandemic, the high variability in results and the evidence of publication bias make it difficult to draw definitive conclusions. More research is needed to understand the true impact of the pandemic on ADHD symptoms in children and adolescents.

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An Iranian study team recently conducted a systematic search of the peer-reviewed medical literature to identify studies using DSM-V, DSM-IV, DSM IV-TR, and ICD10 criteria to estimate the prevalence of ADHD among children under 12, and, separately, among adolescents aged 12 through 17.

Meta-analysis of 53 studies combining almost 97,000 children from every continent except Australia produced a prevalence estimate of 7.6% (with a 95% confidence range of 6.1% to 9.4%). An Iranian study team recently conducted a systematic search of the peer-reviewed medical literature to identify studies using DSM-V, DSM-IV, DSM IV-TR, and ICD10 criteria to estimate the prevalence of ADHD among children under 12, and, separately, among adolescents aged 12 through 17.

Meta-analysis of 53 studies combining almost 97,000 children from every continent except Australia produced a prevalence estimate of 7.6% (with a 95% confidence range of 6.1% to 9.4%). There was extensive variation (heterogeneity) between studies, but no indication of publication bias.

Meta-analysis of 25 studies covering a total of over 40,000 adolescents from every continent except Australia produced a prevalence estimate of 5.6% (with a 95% confidence range of 4% to 7.8%). Again, there was extensive variation (heterogeneity) between studies, but no indication of publication bias.

The authors conceded, “One of the limitations of this study is the high heterogeneity of studies in terms of age group. Since the purpose of this study was to measure the prevalence of children and adolescents separately, studies that report the prevalence of ADHD in children and adolescents combined were removed.”

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