UK Nationwide Population Study Finds ADHD Associated with Reduced Life Expectancy

Researchers from the Swedish Department of Global Public Health, the Swedish Transport Agency, and the Swedish National Road and Transport Research Institute collaborated in a nationwide population study of motor vehicle crashes among the elderly, defined as 65 and older.

They availed themselves of the country's all-encompassing national registers to identify the anonymized records of all such drivers from 2011 through 2016. That enabled them to compare crash records of those with known driving-impairing conditions with matched drivers who had no record of such conditions.

They looked only at road traffic crashes that resulted in injury to the driver or a passenger. For anyone with multiple crash records, they only looked at the first.

This was a case-control study, with two controls matched to each case wherever possible. For every case of a 65 or older driver involved in an injurious crash, the team randomly matched two individual controls by sex, birth year, municipality of residence, and other medical conditions. Place of residence was used to distinguish residents of large cities, who would tend to drive less frequently and in denser traffic, from those in small towns and rural areas. To minimize controls that never drive, only those with a driver's license and car were considered.

Of the thirteen medical conditions examined, elderly drivers with "ADHD, autism spectrum disorder, and similar conditions" had by far the highest odds of being in crashes that resulted in injury "at almost three times the rate of those without those conditions."

But note carefully the serious limitations in the data:

• ADHD was bundled in with autism spectrum disorder and "similar conditions", making an unalloyed evaluation impossible.
• Out of a total of 13,701 crashes, only 26 involved any of these conditions.
• Because of the small number, the two-for-one matching broke down completely. Only 17 matched controls could be found, less than a third of the target of 52.
• That means that despite a nationwide sample involving over 40,000 cases and controls, the sample size for "ADHD, autism spectrum disorder and similar conditions" was only 43.

The authors noted that while the high odds ratio "for ADHD, autism spectrum disorder, and similar conditions, are in line with previous studies on young adult drivers and adult drivers in this recent cohort of older, Swedish adults, such conditions are very uncommon compared to younger adults, suggesting likely under-diagnosis. Hence, the results should be interpreted with caution."

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.

Suicide is one of the most feared outcomes of any psychiatric condition. Although its association with depression is well known, a small but growing research literature shows that ADHD is also a risk factor for suicidality.  Suicide is difficult to study. Because it is relatively rare, large samples of patients are needed to make definitive statements.
Studies of suicide and ADHD must also consider the possibility that medications might elevate that risk. For example, the FDA placed a black box warning on atomoxetine because that ADHD medication had been shown to increase suicidal risk in youth.  A recent study of 37,936 patients with ADHD now provides much insight into these issues (Chen, Q., Sjolander, A., Runeson, B., D'Onofrio, B. M., Lichtenstein, P. & Larsson, H. (2014). Drug treatment for attention-deficit/hyperactivity disorder and suicidal behavior: a register-based study. BMJ 348, g3769.). In Sweden, such large studies are possible because researchers have computerized medical registers that describe the disorders and treatments of all people in Sweden. Among 37,936 patients with ADHD, 7019 suicide attempts or completed suicides occurred during 150,721 person-years of follow-up. This indicates that, in any given year, the risk for a suicidal event is about 5%. For ADHD patients, the risk for a suicide event is about 30% greater than for non-ADHD patients. Among the ADHD patients who attempted or completed suicide, the risk was increased for those who had also been diagnosed with a mood disorder, conduct disorder, substance abuse, or borderline personality. This is not surprising; the most serious and complicated cases of ADHD are those that have the greatest risk for suicidal events. The effects of the medication were less clear.  The risk for suicide events was greater for ADHD patients who had been treated with non-stimulant medication compared with those who had not been treated with non-stimulant medication. A similar comparison showed no effect of stimulant medications. This first analysis suffers from the fact that the probability of receiving medication increases with the severity of the disorder. To address this problem, the researchers limited the analyses to ADHD patients who had some medication treatment and then compared suicidal risk between periods of medication treatment and periods of no medication treatment. This analysis found no increased risk for suicide from non-stimulant medications and, more importantly, found that for patients treated with stimulants, the risk for suicide was lower when they were taking stimulant medications. This protective effect of stimulant medication provides further evidence of the long-term effects of stimulant medications, which have also been shown to lower the risks for traffic accidents, criminality, smoking, and other substance use disorders.