October 30, 2023

Methylphenidate is associated with reduced risk of all-cause mortality in youths with ADHD in a nationwide population cohort study

Youths with ADHD are at higher risk of suicide, burn injuries, road injuries, and more generally all-cause mortality than normally developing children. Methylphenidate (MPH) is known to be effective in reducing ADHD symptoms. Can it also reduce the risk of all-cause mortality? A team of Taiwanese researchers, collaborating with two British researchers, explored that question by looking at a nationwide population cohort.

Taiwan has a single-payer national health insurance system that includes the entire population (99.6 percent coverage). Using the National Health Insurance Research Database (NHIRD), the team identified over 183,000 youths under 18 with an ADHD diagnosis. Of these, just over 68,000 had been prescribed to MPH. The team matched them with an equal number of ADHD youths who were not prescribed MPH. All records were anonymized and checked against the National Mortality Register.

All-cause mortality was split into two subcategories. Unnatural-cause mortality consisted of homicide, suicide, and motor vehicle fatalities. Natural-cause mortality encompassed all other premature deaths. In the raw data, ADHD youths on MPH had half the all-cause mortality of those not on MPH. Natural-cause mortality was down about 40 percent and unnatural-cause mortality was by almost two-thirds. In the non-MPH group, 32 committed suicide in the follow-up year, versus only a single individual in the MPH group. There were seven homicide victims in the non-MPH group, versus none at all in the MPH group.

These staggering reductions, however, were almost exclusively among males. The team then adjusted for potential confounding variables - gender, age, residence, insurance premium, out-patient visits, and pre-existing diagnoses. In the adjusted model, the risk for all-cause mortality was still reduced - by about 20 percent - for those on MPH and remained statistically significant. Virtually identical reductions were found for males and for children first diagnosed with ADHD between 4 and 7 years old. But all other risk estimates became statistically non-significant, due in large measure to the rarity of mortality events.

The authors concluded, "This is the first study reporting that a longer interval between first ADHD diagnosis and first prescription of MPH is associated with a higher risk of all-cause mortality. In addition, we also found that participants receiving longer-duration MPH treatment had a lower risk of all-cause mortality. ... an implication is that receiving a diagnosis earlier and receiving medication earlier may reduce the risk of later adverse consequences."

They nevertheless cautioned, "although we adjusted for multiple covariant, information lacking in the database precluded the measurement of other possible confounders, such as family history, psychosocial stressors, the effect of behavioral therapy or severity of comorbidities. Therefore, as with all observational data, it is not possible to be conclusive about whether the association with lower mortality is related to an effect of MPH treatment itself or whether other characteristics of the children receiving MPH may account for the lower risk (i.e. confounding by indication).

Finally, although the cohort sizes were large, the number of deaths was small, and this limited statistical power, particularly for the investigation of cause-specific mortality and of subgroup differences. Because of the relatively low number of deaths and limited follow-up duration, longer-term studies with larger samples are warranted ..."

Vincent Chin-HungChen, Hsiang-Lin Chan, Shu-I Wu, Mong-Liang Lu, Michael E. Dewey, Robert Stewart, and Charles Tzu-Chi Lee, "Methylphenidate and mortality in children with the attention-deficit hyperactivity disorder: a population-based cohort study," British Journal of psychiatry (2020), https://doi.org/10.1192/bjp.2020.129.

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Updated Analysis of ADHD Prevalence in The United States

The National Health Interview Survey (NHIS) is conducted annually by the National Center for Health Statistics at the Centers for Disease Control and Prevention. The NHIS is done primarily through face-to-face computer-assisted interviews in the homes of respondents. But telephone interviews are substituted on request, or where travel distances make in-home visits impractical.  

For each interviewed family, only one sample child is randomly selected by a computer program.  

The total number of households with a child or adolescent aged 3-17 for the years 2018 through 2021 was 26,422. 

Based on responses from family members, 9.5% of the children and adolescents randomly surveyed throughout the United States had ADHD.  

This proportion varied significantly based on age, rising from 1.5% for ages 3-5 to 9.6% for ages 6-11 and to 13.4% for ages 12-17. 

There was an almost two-to-one gap between the 12.4% prevalence among males and the 6.6% prevalence among females. 

There was significant variation by race/ethnicity. While rates among non-Hispanic whites (11.1%) and non-Hispanic blacks (10.5%) did not differ significantly, these two groups differed significantly from Hispanics (7.2%) and Others (6.6%). 

There were no significant variations in ADHD prevalence based on highest education level of family members. 

But family income had a significant relationship with ADHD prevalence, especially at lower incomes. For family incomes under the poverty line, the prevalence was 12.7%. That dropped to 10.3% for family incomes above the poverty level but less than twice that level. For all others it dropped further to about 8.5%. Although that might seem like poverty causes ADHD, we cannot draw that conclusion.  Other data indicate that adults with ADHD have lower incomes.  That would lead to more ADHD in kids from lower income families.

There was also significant geographic variation in reported prevalence rates. It was highest in the South, at 11.3%, then the Midwest at 10%, the Northeast at 9.1%, with a jump down to 6.9% in the West. 

Overall ADHD prevalence did not vary significantly by year over the four years covered by this study. 

Study Conclusion:

This study highlights a consistently high prevalence of developmental disabilities among U.S. children and adolescents, with notable increases in other developmental delays and co-occurring learning and intellectual disabilities from 2018 to 2021. While the overall prevalence remained stable, these findings emphasize the need for continued research into potential risk factors and targeted interventions to address developmental challenges in youth.

It is also important to note that this study assessed the prevalence of ADHD being diagnosed by healthcare professionals.  Due to variations in healthcare accessibility across the country, the true prevalence of ADHD may differ still.

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March 7, 2025

Study Finds ADHD Associated With Sleep Issues, but Reports Improvement with Medication

Large U.S. Cohort Study Finds ADHD Associated With Sleep Insufficiency and Bedtime Irregularity, but Reports Improvement with ADHD Medication

Background:

An international research team used the nationally representative 2020–2021 U.S. Survey of Children’s Health to explore associations between ADHD, weeknight sleep insufficiency, and bedtime irregularity. 

"Sleep sufficiency" refers to the recommended amount of sleep for an individual. Sleep recommendations vary by age and other factors, such as health and lifestyle. For example, 7-9 hours is typically considered sufficient sleep for most adults, but an active teen may require closer to 10 hours of sleep per day.

Previous studies have shown that issues with both falling and staying asleep are common in individuals with ADHD.

The Study:

The team matched 7,671 children and adolescents with ADHD aged 3-17 to 51,572 controls.  

Noting that “The few available population-based studies examining sleep in children with ADHD have focused on circumscribed age ranges, limiting generalizability across childhood, and have seldom included controls,” and “bedtime irregularity has received limited empirical attention in children with ADHD,” this study focused on these aspects of sleep impairment. 

The study group excluded children and adolescents with ADHD with Down syndrome, current or lifetime cerebral palsy, and current or lifetime intellectual disability. In the control group, it excluded individuals with Down syndrome, cerebral palsy, intellectual disability, speech and language disorder, autism spectrum disorder, ADHD, anxiety, depression, behavioral or conduct problems, Tourette syndrome, and use of mental health services in the preceding 12 months. These groups were excluded to limit potential confounding factors.

After adjustment for covariates, parents of children and adolescents with ADHD reported weekday sleep insufficiency 65% more frequently than parents of controls.  

However, when comparing matched controls with children and adolescents with ADHD who were being treated with ADHD medication, there was no significant difference. 

Similarly, there was a small but significant effect size increase in bedtime irregularity among children and adolescents with ADHD relative to their matched controls. 

Yet there was also a small but significant effect size decrease in bedtime irregularity among those taking medication for ADHD relative to those who were unmedicated. 

The team noted, “Interestingly, here, ADHD medication use was linked to less bedtime irregularity across full and age-stratified samples, and not related to sleep insufficiency. However, research indicates the association between stimulant use and sleep problems is attenuated with longer duration of use, and also suggests the potential for stimulants to produce positive effects on sleep through reduced bedtime resistance. Further, ADHD medication type, not specified, may have influenced outcomes.” 

The Take-Away:

The study concluded that ADHD in children was linked to insufficient sleep and irregular bedtimes in a nationally representative sample, reinforcing and expanding previous research. The findings emphasize the influence of various factors on sleep insufficiency and bedtime irregularity, including race, screen time, poverty, ADHD severity, and depression.

February 28, 2025

Unmedicated Adult ADHD Linked to Dementia in Population Study

Background:

Noting that “the association between adult ADHD and dementia risk remains a topic of interest because of inconsistent results,” an Israeli study team tracked 109,218 members of a nonprofit Israeli health maintenance organization born between 1933 and 1952 who entered the cohort on January 1, 2003, without an ADHD or dementia diagnosis and were followed up to February 28, 2020. 

Israeli law forbids nonprofit HMOs from turning anyone away based on demographic factors,  health conditions, or medication needs, thereby limiting sample selection bias.  

The estimated prevalence of dementia in this HMO, as diagnosed by geriatricians, neurologists, or psychiatrists, is 6.6%. This closely matches estimates in Western Europe (6.9%) and the United States (6.5%). 

Method:

The team considered, and adjusted for, numerous covariates: age, sex, socioeconomic status, smoking, depression, obesity, chronic obstructive pulmonary disease, hypertension, atrial fibrillation, heart failure, ischemic heart disease, cerebrovascular disease, diabetes, Parkinson’s disease, traumatic brain injury, migraine, mild cognitive impairment, psychostimulants. 

With these adjustments, individuals diagnosed with ADHD were almost three times as likely to be subsequently diagnosed with dementia as those without ADHD. Men with ADHD were two and a half times more likely to be diagnosed with dementia, whereas women with ADHD were over three times more likely, than non-ADHD peers. 

More concerning still, persons with ADHD were 5.5 times more likely to be subsequently diagnosed with early onset dementia, as opposed to 2.4 times more likely to be diagnosed with late onset dementia. 

On the other hand, the team found no significant difference in rates of dementia between individuals with ADHD who were being treated with stimulant medications and individuals without ADHD. Those with untreated ADHD had three times the rate of dementia. The team nevertheless cautioned, “Due to the underdiagnosis of dementia as well as bidirectional misdiagnosis, this association requires further study before causal inference is plausible.” 

Conclusions and Relevance:

This study reinforces existing evidence that adult ADHD is associated with an increased risk of dementia. Notably, the increased risk was not observed in individuals receiving psychostimulant medication, however the mechanism behind this association is not clear.

These findings underscore the importance of reliable ADHD assessment and management in adulthood. They also highlight the need for further study into the link between stimulant medications and the decreased risk of dementia.

 

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February 25, 2025