Cookie Preferences
By clicking, you agree to store cookies on your device to enhance navigation, analyze usage, and support marketing. More Info
Thank you! Your submission has been received!
Oops! Something went wrong while submitting the form.
May 31, 2021
To what extent are ADHD medications insufficiently used to address properly diagnosed ADHD? To what extent are they misused by persons who are either undiagnosed or improperly diagnosed? In search of answers, an international team of researchers from Brazil, the United Kingdom, and the United States conducted a systematic review of the peer-reviewed literature and a meta-analysis of studies from four continents - South America, North America, Europe, and Australia.
The benchmarks set for proper ADHD diagnosis were any of the following:
· Criteria established in the Diagnostic and Statistical Manual of Mental Disorders (DSM)or the International Statistical Classification of Diseases and Related Health Problems (ICD), confirmed by validated diagnostic instruments or clinical interviews.
· Use of validated ADHD symptom scales with pre-specified thresholds.
· Participants or caregivers affirming ADHD diagnosis by a physician.
Medications reviewed were those recommended by the majority of the international guidelines-both stimulant(methylphenidate, dexmethylphenidate, amphetamines), and non-stimulant (atomoxetine).
The team excluded studies relying on the insurance health system and third-party reimbursement datasets because the focus was on rates of ADHD medication use in the entire population rather than among individuals searching for treatment.
A meta-analysis of 18 studies with a total of 3,311 children and adolescents properly diagnosed with ADHD in seven countries on four continents (Canada, United States, Australia, Brazil, Netherlands, England, Venezuela) found an overall pharmacological treatment rate of only 19%. There was considerable variation, with the highest treatment rates in the United States (frequently over 40%) and the lowest treatment rates in Brazil, Venezuela, and Canada (under 10%). There was no sign of publication bias.
A second meta-analysis pooled 14 studies with a total of 29,559 children and adolescents without a proper diagnosis of ADHD in five countries on four continents (United States, Canada, Venezuela, Australia, Netherlands). Roughly 1% were using ADHD medications. Again, there was considerable variation, with the highest rates of medication misuse being reported in the United States and Venezuela (3-7%). Again, there was no sign of publication bias.
The authors cautioned, "it is important to note that even though the data collected constitute the most comprehensive evidence available in the literature and response/completion rates observed are acceptable, it does not constitute a world representative sample." Also, the predominance of samples from prosperous countries "most certainly inflates the treatment rates due to the exclusion of a large proportion of the world population with significant financial, cultural, and health access barriers to ADHD treatment."
They concluded, "Despite these limitations, our meta-analysis provides evidence for substantial under-treatment of children and adolescents affected by ADHD in different countries. This is a relevant public health issue worldwide since ADHD under treatment is associated with known negative outcomes in education, healthcare, and productivity systems. At the same time, we found evidence of overtreatment/misuse in individuals without a formal ADHD diagnosis. This practice might expose individuals to undesirable side effects of medications, increased risk of medication misuse, and unmeasured costs for the health care system."
RafaelMassuti, Carlos RenatoMoreira-Maia, FaustoCampani, MárcioSônego, JuliaAmaro, GláuciaChiyokoAkutagava-Martins, LucaTessari, Guilherme V.Polanczyk, SamueleCortese, Luis Augusto Rohde, “Assessing undertreatment and overtreatment/misuse of ADHD medications in children and adolescents across continents: A systematic review and meta-analysis,” Neuroscience &Biobehavioral Reviews(2021), Vol. 128, 64-73, published online ahead of print, https://doi.org/10.1016/j.neubiorev.2021.06.001.
A Chinese research team performed two types of meta-analyses to compare the risk of suicide for ADHD patients taking ADHD medication as opposed to those not taking medication.
The first type of meta-analysis combined six large population studies with a total of over 4.7 million participants. These were located on three continents - Europe, Asia, and North America - and more specifically Sweden, England, Taiwan, and the United States.
The risk of suicide among those taking medication was found to be about a quarter less than for unmediated individuals, though the results were barely significant at the 95 percent confidence level (p = 0.49, just a sliver below the p = 0.5 cutoff point). There were no significant differences between males and females, except that looking only at males or females reduced sample size and made results non-significant.
Differentiating between patients receiving stimulant and non-stimulant medications produced divergent outcomes. A meta-analysis of four population studies covering almost 900,000 individuals found stimulant medications to be associated with a 28 percent reduced risk of suicide. On the other hand, a meta-analysis of three studies with over 62,000 individuals found no significant difference in suicide risk for non-stimulant medications. The benefit, therefore, seems limited to stimulant medication.
The second type of meta-analysis combined three within-individual studies with over 3.9 million persons in the United States, China, and Sweden. The risk of suicide among those taking medication was found to be almost a third less than for unmediated individuals, though the results were again barely significant at the 95 percent confidence level (p =0.49, just a sliver below the p = 0.5 cutoff point). Once again, there were no significant differences between males and females, except that looking only at males or females reduced the sample size and made results non-significant.
Differentiating between patients receiving stimulant and non-stimulant medications once again produced divergent outcomes. Meta-analysis of the same three studies found a 25 percent reduced risk of suicide among those taking stimulant medications. But as in the population studies, a meta-analysis of two studies with over 3.9 million persons found no reduction in risk among those taking non-stimulant medications.
A further meta-analysis of two studies with 3.9 million persons found no reduction in suicide risk among persons taking ADHD medications for 90 days or less, "revealing the importance of duration and adherence to medication in all individuals prescribed stimulants for ADHD."
The authors concluded, "exposure to non-stimulants is not associated with a higher risk of suicide attempts. However, a lower risk of suicide attempts was observed for stimulant drugs. However, the results must be interpreted with caution due to the evidence of heterogeneity ..."
With the growth of the Internet, we are flooded with information about attention deficit hyperactivity disorder from many sources, most of which aim to provide useful and compelling "facts" about the disorder. But, for the cautious reader, separating fact from opinion can be difficult when writers have not spelled out how they have come to decide that the information they present is factual.
My blog has several guidelines to reassure readers that the information they read about ADHD is up-to-date and dependable. They are as follows:
Nearly all the information presented is based on peer-reviewed publications in the scientific literature about ADHD. "Peer-reviewed" means that other scientists read the article and made suggestions for changes and approved that it was of sufficient quality for publication. I say "nearly all" because in some cases I've used books or other information published by colleagues who have a reputation for high-quality science.
When expressing certainty about putative facts, I am guided by the principles of evidence-based medicine, which recognizes that the degree to which we can be certain about the truth of scientific statements depends on several features of the scientific papers used to justify the statements, such as the number of studies available and the quality of the individual studies. For example, compare these two types of studies. One study gives drug X to 10 ADHD patients and reported that 7 improved. Another gave drug Y to 100 patients and a placebo to 100 other patients and used statistics to show that the rate of improvement was significantly greater in the drug-treated group. The second study is much better and much larger, so we should be more confident in its conclusions. The rules of evidence are fairly complex and can be viewed at the Oxford Center for Evidenced Based Medicine (OCEBM;http://www.cebm.net/).
The evidenced-based approach incorporates two types of information: a) the quality of the evidence and b) the magnitude of the treatment effect. The OCEBM levels of evidence quality are defined as follows (higher numbers are better:
Non-randomized, controlled studies. In these studies, the treatment group is compared to a group that receives a placebo treatment, which is a fake treatment not expected to work.
It is possible to have high-quality evidence proving that a treatment works but the treatment might not work very well. So it is important to consider the magnitude of the treatment effect, also called the "effect size" by statisticians. For ADHD, it is easiest to think about ranking treatments on a ten-point scale. The stimulant medications have a quality rating of 5 and also have the strongest magnitude of effect, about 9 or 10.Omega-3 fatty acid supplementation 'works' with a quality rating of 5, but the score for the magnitude of the effect is only 2, so it doesn't work very well. We have to take into account patient or parent preferences, comorbid conditions, prior response to treatment, and other issues when choosing a treatment for a specific patient, but we can only use an evidence-based approach when deciding which treatments are well-supported as helpful for a disorder.
Older adults are at greater risk for cardiovascular disease. Psychostimulants may contribute to that risk through side effects, such as elevation of systolic blood pressure, diastolic blood pressure, and heart rate.
On the other hand, smoking, substance abuse, obesity, and chronic sleep loss - all of which are associated with ADHD - are known to increase cardiovascular risk, and stimulant medications are an effective treatment for ADHD.
So how does this all shake out? A Dutch team of researchers sets out to explore this. Using electronic health records, they compared all 139 patients 55 years and older at PsyQ outpatient clinic, Program Adult ADHD, in The Hague. Because a principal aim of the study was to evaluate the effect of medication on cardiovascular functioning after first medication use, the 26 patients who had previously been prescribed ADHD medication were excluded from the study, leaving a sample size of 113.
The ages of participants ranged from 55 from 79, with a mean of 61. Slightly over half were women. At the outset, 13 percent had elevated systolic and/or diastolic blood pressure, 2 percent had an irregular heart rate, 15 percent had an abnormal electrocardiogram, and 29 percent had some combination of these (a "cardiovascular risk profile"), and 21 percent used antihypertensive medication.
Three out of four participants had at least e comorbid disorder. The most common are sleep disorders, affecting a quarter of participants, and unipolar mood disorders (depressive or more rarely manic episodes, but not both), also affecting a quarter of participants.
Twenty-four patients did not initiate pharmacological treatment. Of the 89 who received ADHD medication, 58 (65%) reported positive effects, and five experienced no effect. Thirty-eight (43%) discontinued ADHD medication while at the clinic due to lack of effect or to side effects. The most commonly reported positive effects were enhanced concentration, more overview, less restlessness, more stable mood, and having more energy. The principal reasons for discontinuing medication were anxiety/depression, cardiovascular complaints, and lack of effect.
Methylphenidate raised heart rate and lowered weight, but had no significant effect on systolic and diastolic blood pressure. Moreover, there was no significant correlation between methylphenidate dosage and any of these variables, nor between methylphenidate users taking hypertensive medication and those not taking such medication. There was no significant difference in systolic or diastolic blood pressure and heart rate before and after the use of methylphenidate among patients with the cardiovascular risk profiles.
Systolic blood pressure rose in ten out of 64 patients, with two experiencing an increase of at least 20 mmHg. It descended in five patients, with three having a decrease of at least 20 mmHg. Diastolic blood pressure rose by at least 10 mmHg in four patients, while dropping at least 10 mmHg in five others.
The authors concluded "that the use of a low dose of ADHD-medication is well tolerated and does not cause clinically significant cardiovascular changes among older adults with ADHD, even among those with an increased cardiovascular risk profile. Furthermore, our older patients experienced significant and clinically relevant improvement of their ADHD symptoms using stimulants, comparable with what is found among the younger age group," and that "the use of methylphenidate may be a relatively safe and effective treatment for older adults with ADHD, under the condition that all somatic complaints and especially cardiovascular parameters are monitored before and during pharmacological treatment."
Yet they cautioned that "due to the observational nature of the study and the lack of a control group, no firm conclusions can be drawn as to the effectiveness of the stimulants used. ... Important factors that were not systematically reported were the presence of other risk factors, such as smoking, substance (ab)use, aspirin use, and level of physical activity. In addition, the response to medication was not systematically measured"
ADHD affects both individuals and society in many ways. Children and adolescents with ADHD often struggle with focusing, controlling impulses, and staying organized, which leads to problems with schoolwork, learning, and taking tests. These challenges can cause academic failure and make it harder for them to stay in school.
ADHD symptoms often continue into adulthood, affecting jobs, relationships, and increasing risks for substance abuse and legal problems.
Families of children and adolescents with ADHD face extra stress, with parents more likely to experience depression, anxiety, and relationship difficulties. The economic impact is also large, with billions spent each year on medical care, special education, lost productivity, and other related costs.
Current treatments for ADHD mostly include medication, behavioral therapy, and educational support. While medications like stimulants can help control ADHD symptoms in the short term, they often cause side effects such as loss of appetite, trouble sleeping, slowed growth, cardiovascular risks, and potential substance dependence. These issues can make it hard for children and adolescents to stay on their medication, and about a third either don’t respond well or can’t tolerate the side effects. Once medication is stopped, the benefits fade quickly and do not lead to lasting improvements in executive functions (thinking skills).
Behavioral therapy and parent training can help with behavior problems, but have limited effects on core mental skills like planning and self-control. These approaches also tend to be expensive, require a lot of support from parents and teachers, and are hard to use widely in schools and communities that lack resources.
Recently, exercise interventions have attracted growing interest as a non-pharmacological option. They provide several benefits: no drug-related side effects, easy accessibility, low cost, simple implementation in schools and communities, and enhanced physical and mental health.
Previous meta-analyses examining how exercise interventions affect children and adolescents with ADHD have used traditional univariate models, which treat each study as if it only offers one independent effect size. In contrast, this study used multilevel meta-analysis — a more advanced statistical method modelling both between-study and within-study effects. This approach results in more accurate estimates and more dependable conclusions.
Eligible studies were randomized controlled trials (RCTs) with usual care, no intervention, or waitlist controls, involving children and adolescents aged 5–18 diagnosed with ADHD by internationally recognized diagnostic criteria, and reporting inhibitory control outcomes.
Eleven studies combining 512 children and adolescents met these inclusion standards.
The analysis between experimental and control groups indicated that the exercise intervention group had significantly improved inhibitory control performance compared to the control group, with a medium-to-large effect size. There was very little variation (heterogeneity) in outcome between the studies, and no sign of publication bias.
Within-group analyses showed that experimental groups had significant improvements after the intervention compared to baseline, with large effect sizes and moderate heterogeneity.
By comparison, analyzing control groups over the same period revealed no significant differences, indicating that inhibitory control abilities in these groups remained largely unchanged throughout the observation period. There was little heterogeneity.
Nevertheless, only one of the studies was rated low risk of bias, nine had some concerns, and two were rated high risk of bias. The greatest shortcomings were a lack of blinding and preregistration.
The study authors therefore concluded that the overall evidence quality of this meta-analysis is low, limiting confidence in the results. While exercise interventions seem to improve inhibitory control abilities in children and adolescents with ADHD, significant methodological limitations create uncertainty about the effect size. These require more rigorous future studies to clarify these effects. Despite these caveats, they noted that all included studies reported statistically significant, consistent benefits from exercise interventions, offering preliminary support for their use as an adjunctive approach.
Takeaway
This study lands in the same conversation as the adult ADHD exercise meta-analysis, and together they start to form a coherent picture: exercise appears to support attention and impulse control across the lifespan for people with ADHD, not just in one age group. The honest caveat is that the research quality in this field is still catching up to the enthusiasm — most studies have design weaknesses that limit confidence in the exact size of the effect. But the consistency of findings across studies, age groups, and now two separate meta-analyses is hard to dismiss.
A new study in the respected journal PLOS One analyzes data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) to examine trends in the incidence, prevalence, and disability-adjusted life-years associated with ADHD among adolescents and young adults aged 10 to 24 years between 1990 and 2021.
The GBD 2021, released by the Institute for Health Metrics and Evaluation (U.S.), is a comprehensive global analysis of 371 diseases, injuries, and risk factors – such as ADHD – across 204 countries from 1990 to 2021. Its open-source data are publicly available.
First, a distinction. Incidence measures the number of new cases of a disease that develop in a specific population each year. Prevalence measures the total number of existing cases – both new and pre-existing – in a population each year.
The estimated global incidence of ADHD declined marginally from 12.61 per 100,000 population in 1990 to 11.89 per 100,000 population in 2021, representing an average annual decrease of 0.6% in age-standardized incidence. The rates observed were comparable between males and females.
Regional trends varied: Western Europe had the highest rise in ADHD incidence (0.5% annually), while North Africa and the Middle East saw the largest drop (0.7% annually). Overall, a higher Socio-Demographic Index (SDI) is linked to a greater incidence, although it is far from a perfect fit. Nationally, showed the highest increase in ADHD incidence (1.15% annually), while Qatar showed the largest decrease with an annualized reduction of 1.77%.
The estimated global prevalence of ADHD declined marginally from 2.38% in 1990 to 2.17% in 2021. Again, the decline was similar for males and females, and across all age groups (10-14, 15-19, 20-24). Higher SDI was associated with higher prevalence, but inconsistently.
Disability-adjusted life-years (DALYs) combine years lost from early death and years lived with disability to measure disease burden. Globally, the age-standardized DALYs rate for ADHD decreased slightly from 30.3 per 100,000 population to 26.6 per 100,000 population, for an average annual decline of 0.6%. The decline occurred across age groups and was similar between males and females.
The authors concluded that ADHD rates and related health burdens have generally declined over the past quarter century, though recent patterns are less consistent due to factors like socioeconomic changes and evolving diagnostic standards. Continued research is needed to improve the accuracy and accessibility of ADHD diagnosis and treatment to further reduce its global impact.
Take-Away:
The broader takeaway is one of cautious reassurance. Despite rising public awareness and diagnosis rates in many Western countries, the global picture over 25 years shows a gentle decline in ADHD burden among young people as opposed to a crisis of escalating proportions as social media may make one think. That said, the variation between regions suggests that access to diagnosis, cultural factors, and reporting standards are shaping the numbers as much as underlying biology. Progress is real but uneven, and the work of improving equitable access to diagnosis and care is far from finished.
The first few weeks of life are the time when babies are most vulnerable to seizures (known as neonatal seizures). This is partly because of events that can occur during birth, and partly because the newborn brain is naturally in a more excitable state than a mature brain, making it more prone to seizure activity.
Seizures affect roughly 1 to 3 in every 1,000 full-term babies born, and the rate is considerably higher in premature babies, at around 11 to 14 per 1,000. In most cases, seizures at this age are triggered by a specific event or injury affecting the brain. In full-term newborns, the most common cause is a condition called hypoxic-ischemic encephalopathy (HIE), which occurs when the brain is deprived of adequate oxygen and blood flow around the time of birth. Other causes include genetic or metabolic conditions, stroke, bleeding in the brain, and structural abnormalities in how the brain developed. In very premature babies, bleeding into the fluid-filled spaces of the brain (known as intraventricular hemorrhage) is the leading culprit.
Diagnosing seizures in newborns is tricky because many normal or abnormal movements and behaviors in this age group can look like seizures without actually being them. For this reason, monitoring the baby’s brain activity using an electroencephalogram (EEG) – a test that records electrical signals in the brain – is essential to confirm whether a seizure is truly occurring.
Sweden’s single-payer health system provides universal coverage, with national registers linking healthcare and population data. Researchers tracked infants with EEG/aEEG-confirmed seizures born between 2009 and 2020 and compared them to controls without neonatal seizures.
Altogether, 1062 infants with neonatal seizures were matched with 5310 controls.
The team adjusted for birth, mode of delivery, sex, birth weight, and Apgar scores – quick, standardized assessments used to evaluate newborns’ health minutes after birth.
With these adjustments, infants who had neonatal seizures were twice as likely to subsequently be diagnosed with ADHD and three times as likely to be subsequently diagnosed with autism spectrum disorder.
The authors emphasized that because the study was observational, it cannot demonstrate a direct cause-and-effect relationship between neonatal seizures and outcomes. Factors like seizure frequency, genetics, and socioeconomic status are thought to significantly impact the prognosis of affected children, but these could not be included in this study due to data limitations.
_logo%201.svg)
