December 11, 2021

Nationwide cohort study: methylphenidate reduces traffic accidents in persons with ADHD

Taiwan has a single-payer healthcare system that covers virtually every inhabitant (99.5%). That makes it relatively easy to track healthcare issues using its comprehensive National Health Insurance Research Database.

This database maintains a subset, the Longitudinal Health Insurance Database (LHID), consisting of a million persons, with no significant differences in sex, age, or healthcare use from the parent database.

A Taiwanese research team used the LHID to identify 114,486 individuals diagnosed with ADHD from 1997 to 2013. It then compared their motor vehicle (including motorcycles, which are extremely common in Taiwan) crash patterns with 338,261 normally developing controls from the same database.

Adjusting for sex, age, and psychiatric comorbidities, persons with ADHD were about a fifth (19%)more likely to be in traffic crashes. Breaking it down further by sex, women with ADHD were no more likely to be in crashes, but men with ADHD were about a quarter (24%) more likely than their healthy counterparts.

Since the database also tracks pharmaceutical prescriptions, the team also looked into the effect of methylphenidate (MPH), the medication that is the first-line treatment for ADHD under Taiwanese guidelines, and the only approved stimulant. Atomoxetine, a non-stimulant, is used where MPH is either ineffective or not indicated for any other reason and is only used in 4% of all cases.

Of the 114,486 persons diagnosed with ADHD, 89,826 used MPH, and 24,660 did not.

Compared with persons with ADHD who were not on methylphenidate, those with ADHD who were on MPH for 180 days (roughly half a year) or less had 77% fewer accidents, and those on MPH for over 180 days had 93% fewer accidents. This strong dose-response relationship is suggestive of a causal relationship, with MPH perhaps reducing impulsive behavior, particularly among young men with ADHD.

The team also conducted within-person analyses, comparing times when persons with ADHD were taking MPH with periods when they were not. These showed no effect within 30 days of use, rising to a 65%reduction in crashes within 60 to 90 days of use, which was barely outside the 95% confidence interval (p = .07), very likely because of "the extremely low incidence of transport accidence (i.e. 0.6%)enlarged the confidence interval."

The authors concluded, "All registration medical claim data came from the nationally-representative sample of NHI, minimizing the selection and recall bias. By excluding transport accidents before ADHD diagnosis, we have precluded the reverse association between ADHD and road traffic accidents as much as possible. The advantage of the between-subjects comparison was that we were able to examine the MPH effect in different dose groups. However, confounding by indication cannot be eliminated. For example, those with a severe degree of ADHD symptoms, an exhibition of risky behaviors, or comorbid with other psychiatric illnesses were more likely to be prescribed medication. Hence, we also performed within-subject comparisons to adjust for time-invariant factors."

Transport safety thus offers another compelling reason to treat ADHD symptoms. Methylphenidate in particular seems to be especially effective in reducing traffic fatalities and injuries.

Yi-Chun Liu, Vincent Chin-Hung Chen, Yao-Hsu Yang, Yi-LungChe, and Michael Gossop, "Association of psychiatric comorbidities with the risk of transport accidents in ADHD and MPH," Epidemiology and PsychiatricSciences30 (2021), e14, 1-9,https://doi.org/10.1017/S2045796021000032.

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Taiwan Nationwide Population Study Finds Link Between ADHD and Early Puberty, Also Protective Effect of Methylphenidate

Precocious puberty (PP) is defined as the onset of secondary sex characteristics before age 8 in girls or age 9 in boys.  

Because it accelerates skeletal maturation by prematurely shutting down the cartilage growth plate at the tip of long bones, it tends to lead to shorter height in adulthood. It is also known to place an additional psychological burden on children, especially girls. Girls are four to 38 times more likely to develop PP than boys. 

Taiwan has a single-payer national health insurance system, called National Health Insurance, that encompasses 99.6% of the island’s population. The Ministry of Health and Welfare uses it to maintain the National Health Insurance Research Database (NHIRD), enabling researchers to conduct nationwide population studies. 

Using this database, a Taiwanese study team investigated the relationship between ADHD and precocious puberty among children and adolescents (under 18). And because methylphenidate (MPH) is the only psychostimulant approved for the treatment of ADHD in Taiwan, the team also explored the effect of MPH on this relationship. 

Most diagnoses of ADHD in the NHIRD are made by board-certified psychiatrists, enhancing diagnostic validity. 

Of the more than 3.3 million persons born in Taiwan between 1997 and 2001, 186,681 were diagnosed with ADHD. Of these, 122,302 were prescribed MPH. 

After adjusting for sex, low-income households, and neuropsychiatric comorbidities, children diagnosed with ADHD were twice as likely to be diagnosed with PP. This held equally true for boys and girls. 

However, children diagnosed with ADHD and prescribed MPH were more than a third less likely to subsequently be diagnosed with PP than those diagnosed with ADHD but not prescribed MPH.  

For girls with ADHD, who without an MPH prescription were nine times more likely than boys with ADHD to be diagnosed with PP, an MPH prescription reduced that ratio to five times more likely than boys with ADHD and prescribed MPH. 

That suggests a strong protective effect of MPH.  

The team concluded, “Our study found that children with ADHD were at a greater risk of PP, and girls with ADHD were a particularly vulnerable group. … MPH appeared to be protective against PP in patients with ADHD, especially in girls. However, these preliminary results need further validation.” 

Taiwan Nationwide Population Study Finds No Effect of Maternal and Childhood Infection on Subsequent Offspring ADHD in Sibling Comparisons

Population Study Finds No Effect of Maternal and Childhood Infection on Subsequent Offspring ADHD

Maternal infections and inflammatory responses during pregnancy have been proposed as risk factors for neurodevelopmental disorders such as ADHD. 

Taiwan has a single-payer health insurance system that covers virtually the entirety of its population. Its Ministry of Health and Welfare maintains the National Health Insurance Research Database (NHIRD), with detailed information on outpatient services, hospitalizations, and medical treatment for nearly 99% of all residents. 

A Taiwanese study team used NHIRD to examine to examine the relationship between maternal hospitalization for infection, and early childhood infection, and subsequent ADHD in offspring. The study cohort originated with all 3,260,879 individuals born between 2001 and 2018. 

The team excluded births from foreign mothers, still births, births with congenital defects, low birth weights, abnormally late births, twins, triplets, and other multiple births, culminating in a final population cohort of 2,885,662 live-born single infants across 1,893,171 families, and 1,864,660 individuals with full siblings from 872,169 families comprising the full sibling cohort. 

Study participants were followed until diagnosis of a neurodevelopmental disorder, their death, or the end of 2021. 

After adjusting for sex, birth year, paternal and maternal ages, birthweight, birth season, parity, delivery method, 1 minute APGAR score (evaluating baby’s appearance, pulse, grimace, activity and respiration at birth), gestational age, pregnancy and delivery complications, parental history of neurodevelopmental disorders, maternal asthma and diabetes, urbanization level of the residential area, and family’s insurance amount, offspring of mothers hospitalized for infections had 14% greater odds of being subsequently diagnosed with ADHD. 

However, in the full sibling cohort of over 1.8 million, this association vanished. That held true for each of the three trimesters of pregnancy. It also held true for bacterial infections. Surprisingly, offspring of mothers hospitalized for viral infections were 24% less likely to be diagnosed with ADHD than their siblings not exposed to maternal viral infection. Because of that, they also had a 6% lower risk overall. 

After the same adjustments, early childhood infection was associated with 16% greater odds of being diagnosed with ADHD. 

Nevertheless, in the full sibling cohort of over 1.8 million, this association again vanished. That held true overall, as well as separately for childhood infections in months 1-6 and months 7-12. The association vanished altogether both for bacterial infections as well as for viral infections. 

The authors concluded, “the results of this nationwide birth cohort study with population and sibling analyses suggest that the association between maternal infection during pregnancy and offspring neurodevelopmental risk is largely due to familial confounding factors.” 

March 25, 2025

Australian Nationwide Survey Finds More Than Tenfold Greater Odds of Suicidality or Self-harm Among Children with ADHD

Most previous studies of suicide and self-harm risk among persons with ADHD have focused on adolescents and adults. They’ve also tended to be cross-sectional, analyzing data from a population at a specific point in time. 

An Australian study team took a different approach, conducting a before-and-after study through the birth cohort of the Longitudinal Study of Australian Children (LSAC), comprising 5,107 children who have been followed up every two years since birth. 

The diagnosis of ADHD was based on parents reporting that their child had received a diagnosis of ADHD at or before age ten.  

Suicide and self-harm were defined as children’s self-report at age 14 of any thought or attempt of suicide and self-harm respectively over the past year. 

The team adjusted for the following confounders: socioeconomic status, birth weight, ADHD medication history, maternal education level, maternal age at birth, experience in bullying victimization at age 12, and depression score based on Short Mood and Feelings Questionnaire (SMFQ). 

Of the 5,107 participants, 3,696 had all the valid data required for analysis and were included in the final cohort. Of these, 3.6% were diagnosed with ADHD by age 10. 

With diagnosis of ADHD at age 10 and all other factors held constant: 

  • The odds of suicidal thought, plan, or attempt at age 14 increased elevenfold. This was twice as pronounced among boys as among girls. 
  • The odds of self-harm at age 14 increased 25-fold. This was more than three times as pronounced among boys as among girls. 

Both depression and exposure to bullying were statistically significant mediators for the relationship. Nevertheless, depression and exposure to bullying each accounted for well under 10% of the overall effect. 

Neither socioeconomic status nor maternal factors had any significant mediating effect on outcomes. 

Conclusion:

The authors concluded, “This study provides compelling evidence that children diagnosed with ADHD at the age of 10 years face significantly elevated risks of experiencing suicidal thoughts, planning, or attempts, as well as self-harm, by the age of 14 years, which underscores the critical importance of recognizing and addressing these heightened risks in children with ADHD.” 

While factors like depression and bullying contribute, ADHD itself remains a key risk factor. Early intervention and strong mental health support are crucial to protecting these children’s well-being.

March 21, 2025