Other disorders such as substance use increased the risk of death, but ADHD on its own was an independent risk.
The researchers, led by Søren Dalsgaard from Aarhus University in Denmark, found the relative risk of dying was much higher for women than for men with attention-deficit hyperactivity disorder (ADHD).
Not receiving a diagnosis until adulthood was also associated with higher risk.
The study was a massive cohort study with over 32 years of follow-up of almost 2 million people in the Danish national registers.
The researchers identified 32,061 individuals, with 26% being women, who had ADHD within the nationwide cohort of 1,922,248 people.
The authors calculate that "all-cause mortality rate" (death from all causes) was:
- 5.85 for every 10,000 person-years in people with ADHD
- 2.21 per 10,000 in people without the disorder (controls).
This difference corresponds to a twofold rise in the mortality rate ratio (MRR) in people with ADHD.
For individuals diagnosed at age 18 years or older, the increased likelihood of early death was more than fourfold compared with those without ADHD at the same age. Children diagnosed before the age of 6 years, by contrast, were at around double the risk of death compared with their healthy counterparts.
For people whose ADHD was diagnosed in adulthood, there was an MRR of 4.25, compared with 1.58 for those people diagnosed in childhood.
The authors say this "suggests that ADHD persisting into adulthood often represents a more severe form of the disorder."
Women with ADHD had a higher mortality rate (3.01) than did men with the disorder (1.93). The authors conclude:
"The interactions with age at diagnosis, sex, and comorbid conditions emphasize the importance of early identification of ADHD, especially in girls and women, and treatment of comorbid oppositional defiant disorder, conduct disorder and substance use disorder."
The authors say their study underlines the importance, particularly for females, of early diagnosis and treatment of ADHD.
They caution, however, that the risk of early death, being compared with that for healthy people, does not translate into a high number of people with ADHD dying early - the doubled relative risk of premature death translates into a small absolute risk of early death.
A professor of psychiatry's commentary article on the study in the same issue of The Lancet echoes this point. Dr. Stephen Faraone, director of child and adolescent psychiatry research at SUNY Upstate Medical University in New York, says that although talk of premature death will worry parents and patients, "they can seek solace in the knowledge that the absolute risk for premature death is low and that this and other risks can be greatly reduced with evidenced-based treatments for the disorder."
Dr. Faraone continues:
"For too long, the validity of ADHD as a medical disorder has been challenged. Policy makers should take heed of these data and allocate a fair share of health care and research resources to people with ADHD.
For clinicians, early identification and treatment should become the rule rather than the exception."
The population-based cohort under examination included all children born in Denmark between 1981 and 2011, with almost complete follow-up data for up to 32 years.
The increased death rate with ADHD was mainly driven by deaths from unnatural causes, with accidents being the most common cause of death.
"ADHD is a common neurodevelopmental disorder known to cause impairment across the lifespan," says the authors. "However, this study is the first to note that the disorder itself is also associated with increased mortality, and is highest in individuals diagnosed in adulthood."
The researchers found that individuals with ADHD, but without the comorbidities of oppositional defiant disorder, conduct disorder, or substance use disorder, had increased mortality, but that if these disorders were also present, there was an even higher risk of death - increasing mortality in a "dose-response manner."
Dr. Faraone's commentary asks what the causal link could be between ADHD and early death, citing one pathway that "follows ADHD's well-known risks for oppositional defiant disorder or conduct disorder."
That pathway links ADHD to risk of death as follows. There is an increased risk of:
- Antisocial disorders - which increase the risk of violence and crime
- Substance use - leading to accidents and fighting
- Inattention and impulsivity - increasing accidents and poor health habits
- Risky behaviors - leading to health risks and accidents.
But Dr. Faraone notes that ADHD alone, without leading to the other disorders, was found to increase risk of death independently, and picks out the following features of the disorder that may directly increase the risk of accidents:
- Inattention and impulsivity - which affect driving since when treated with medication, there is better "performance in a driving simulator"
- Risky behaviors associated with "poor effortful control and increased sensation-seeking."
Also noted in the commentary is the higher risk associated with a diagnosis being made later in life - "failure to identify and treat ADHD in a timely manner might worsen the course of the disorder and increase the risk to enter one of the pathways to premature death" listed above, says Dr. Faraone.
This offers an alternative to the explanation given by the study authors that persistent ADHD represents a more severe form of the disorder.
Last June, the American Academy of Pediatrics issued guidance on the care of children with ADHD to prevent substance abuse.
Last month, a study found that almost 1 in 5 adults with epilepsy may have symptoms of ADHD.