May 31, 2021

Assessing Undertreatment and Misuse of ADHD Medications on Four Continents

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.

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ADHD medication and risk of suicide

ADHD medication and risk of suicide

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 ..."

December 13, 2021

What is Evidenced-Based Medicine?

What is Evidenced-Based Medicine?

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:

  1. Mechanism-based reasoning.  For example, some data suggest that oxidative stress leads to ADHD, and we know that omega-3 fatty acids reduce oxidative stress. So there is a reasonable mechanism whereby omega-3 therapy might help ADHD people.
  2. Studies of one or a few people without a control group, or studies that compare treated patients to those that were not treated in the past.

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.  

  1. Non-randomized means that the comparison might be confounded by having placed different types of patients in the treatment and control groups.
  2. A single randomized trial.  This type of study is not confounded.
  3. Systematic review and meta-analysis of randomized trials. This means that many randomized trials have been completed and someone has combined them to reach a more accurate conclusion.

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.

April 23, 2021

How Effective and Safe are Stimulant Medications for Older Adults?

How effective and safe are stimulant medications for older adults?

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"

December 21, 2021

Northern Finnish Population Study Finds ADHD Slashes Higher Education Attainment, Comorbidity of ADHD + ODD much worse

Background:

Although ADHD typically begins in childhood, its symptoms frequently continue into adulthood, and it is widely acknowledged as having a lifelong prevalence for most persons with ADHD. 

ADHD symptoms are linked to poor academic performance, mainly due to cognitive issues like compromised working memory. These symptoms lead to long-term negative academic outcomes and difficulty in achieving higher educational degrees. 

Oppositional Defiant Disorder (ODD) often co-occurs with ADHD. In community samples, it appears in about 50–60% of those with ADHD. ODD symptoms include an angry or irritable mood, vindictiveness toward others, and argumentative or defiant behavior that lasts more than 6 months and significantly disrupts daily life.  

Since ODD tends to co-occur with ADHD, research on pure ODD groups without ADHD is limited, especially in community samples. This longitudinal study aimed to examine the impact of ADHD and ODD symptoms in adolescence on academic performance at age 16 and educational attainment by age 32. 

Study:

Finland, like other Nordic countries, has a single-payer health insurance system that includes virtually all residents. A Finnish research team used the Northern Finnish Birth Cohort to include all 9,432 children born from July 1, 1985, through June 30, 1986, and followed since then. 

ADHD symptoms were measured at age 16 using the Strengths and Weaknesses of ADHD symptoms and Normal-behaviors (SWAN) scale. 

Symptoms of ODD were screened using a 7-point rating scale similar to the SWAN scale, based on eight DSM-IV-TR criteria: “Control temper”, “Avoid arguing with adults”, “Follow adult requests or rules”, “Avoid deliberately annoying others”, “Assume responsibility for mistakes or misbehaviour”, “Ignore annoyances from others”, “Control anger and resentment”, and “Control spitefulness and vindictiveness.” 

Higher education attainments were determined at age 32. 

Results:

After adjusting for the educational attainments of the parents of the subjects, family type, and psychiatric disorders other than ADHD or ODD, males with ADHD symptoms at age 16 had a quarter, and females a little over a third, of the higher education attainments of peers without ADHD symptoms at age 32.  

With the same adjustments, males with ODD symptoms alone had two-thirds, and females 80%, of the higher education attainments of peers without ODD, but neither outcome was statistically significant. 

However, all participants with combined ADHD and ODD symptoms at age 16 had roughly one-fifth of the higher education attainments of peers without such symptoms upon reaching age 32. 

Interpretation: 

The team concluded, “The findings that emerged from this large longitudinal birth cohort study showed that the co-occurrence of ODD and ADHD symptoms in adolescence predicted the greatest deficits of all in educational attainment in adulthood.” 

This study highlights the significant, long-lasting impact that co-occurring ADHD and ODD symptoms can have on educational outcomes well into adulthood. It underscores the importance of addressing both disorders together during adolescence to help improve future academic success.

July 1, 2025

U.S. Nationwide Study Finds Down Syndrome Associated with 70% Greater Odds of ADHD

The Background:

Down syndrome (DS) is a genetic disorder resulting from an extra copy of chromosome 21. It is associated with intellectual disability. 

Three to five thousand children are born with Down syndrome each year. They have higher risks for conditions like hypothyroidism, sleep apnea, epilepsy, sensory issues, infections, and autoimmune diseases. Research on ADHD in patients with Down syndrome has been inconclusive. 

The Study:

The National Health Interview Survey (NHIS) is a household survey conducted by the National Center for Health Statistics at the CDC. 

Due to the low prevalence of Down syndrome, a Chinese research team used NHIS records from 1997 to 2018 to analyze data from 214,300 children aged 3 to 17, to obtain a sufficiently large and nationally representative sample to investigate any potential association with ADHD. 

DS and ADHD were identified by asking, “Has a doctor or health professional ever diagnosed your child with Down syndrome, Attention Deficit Hyperactivity Disorder (ADHD), or Attention Deficit Disorder (ADD)?” 

After adjusting for age, sex, and race/ethnicity, plus family highest education level, family income-to-poverty ratio, and geographic region, children and adolescents with Down syndrome had 70% greater odds of also having ADHD than children and adolescents without Down syndrome. There were no significant differences between males and females. 

The Take-Away:

The team concluded, “in a nationwide population-based study of U.S. children, we found that a Down syndrome diagnosis was associated with a higher prevalence of ASD and ADHD. Our findings highlight the necessity of conducting early and routine screenings for ASD and ADHD in children with Down syndrome within clinical settings to improve the effectiveness of interventions.” 

June 27, 2025

Meta-analysis Explores Link Between ADHD and Homelessness Among Children and Adolescents

An estimated 150 million children and adolescents live on the streets worldwide. In the U.S., roughly 1.5 million experience homelessness annually. Homelessness increases the risk of health issues, violence, early pregnancy, substance use, vaccine-preventable diseases, mental disorders, suicidal behavior, and early death. 

Rates of anxiety, major depression, conduct disorders, and post-traumatic stress disorder are higher among school-age homeless children compared to their housed peers.  

However, there has been limited attention to ADHD, leading a French research team to conduct a systematic review and meta-analysis of its prevalence among homeless children and adolescents.  

The inclusion criteria required that participants be homeless, under 19 years of age at baseline, and have ADHD identified through a screening tool, self-report, or clinical assessment. 

Results:

Meta-analysis of 13 studies with a combined total of 2,878 individuals found indications of ADHD in almost one in four homeless children and adolescents. There was no sign of publication bias, but considerable variation in estimates across studies. 

The team found a dose-response effect. Meta-analysis of six studies with 1,334 participants under 12 years old reported 13% with indications of ADHD. Meta-analysis of five studies encompassing 991 individuals, 12 through 18 years old, found an ADHD rate of 43%. The ADHD rate among adolescents was 3.3 times greater than among children

There were no significant differences among countries. 

Moreover, limiting the meta-analysis to the seven studies with 1,538 participants that relied on clinical ADHD diagnoses, the gold standard,  resulted in an ADHD prevalence of 23%

The team concluded, “The review of 13 studies revealed that ADHD is common in homeless children and adolescents, suggesting that homelessness may contribute to the development or exacerbation of ADHD symptoms. Conversely, ADHD with other comorbidities may increase the likelihood of homelessness. Reintegrating these children and adolescents into care systems and ensuring access to public health interventions tailored for homeless families and youth is imperative for breaking the cycle of homelessness and improving long-term trajectories.” 

In other words, this review not only confirmed a strong link between homelessness and ADHD in children and youth, but also suggested a complex, cyclical relationship. Providing tailored health care and support for these vulnerable groups is crucial to interrupt this cycle and help improve their future outcomes.

June 23, 2025