Premature deaths related to attention deficit-hyperactivity disorder (ADHD) were significantly associated with psychiatric comorbidities in a Swedish registry study.
In a group of more than 2.6 million adults, people with ADHD had a higher risk of dying from both natural (adjusted hazard ratio 2.47, 95% CI 1.66-4 3.68) and unnatural causes (HR 6.48, 95% CI 5.12-8.21) compared with those without ADHD, reported Shihua Sun, MD, of the Karolinska Institutet in Stockholm, Sweden, and colleagues.
Those with ADHD had a 40% higher risk of all-cause mortality, and this increased with each comorbid psychiatric condition, the team wrote online in .
However, just 424 individuals with ADHD and 6,231 without ADHD died during the study.
"No one should get the impression that having ADHD [means being] doomed to die early due to traffic accidents or suicide," Sun told Ƶ in an email. "On the other hand, we do believe that both ADHD and premature death are manageable problems, and most of the premature deaths, at least most deaths due to unnatural causes, can and should be prevented."
Individuals with ADHD have been shown to have a higher risk for comorbid psychiatric disorders, accidents, and suicidal behavior, Sun explained. One found that patients with ADHD were about twice as likely to die prematurely than people without ADHD.
The author of a accompanying the 2015 analysis suggested that antisocial and substance abuse disorders may be related to the correlation.
Indeed, this study found that later-onset psychiatric comorbidities like substance use contributed substantially to the risk of death due to unnatural causes like suicide or unintentional injuries, although the increased risk of death due to unintentional injuries seems to be present also in people who have ADHD but no psychiatric comorbidities, the authors reported.
The apparent vulnerability to substance use disorders may be driven by stress caused by the ADHD itself or dysfunction of the neurotransmission systems, Sun said. When paired with ADHD, other mood disorders may also lead to high-risk behavior or self harm, he added.
Meanwhile, early-onset psychiatric comorbidities like intellectual disabilities were linked to the risk of death due to natural causes like neoplasms, the researchers reported.
For this study, 2,675,615 individuals (51.4% male) born from 1983 to 2009 in Sweden were included, and followed up until death, emigration, or the end of the trial. Sun and his team determined which patients had ADHD (3.2%), mostly through inpatient and outpatient care records, but also through data on medication use (14.1%). The mean age of diagnosis was about 14, and the average follow-up time was around 11 years.
Comorbid psychiatric disorders were much more common in individuals with ADHD versus those without, particularly substance use disorder (13.3% vs 2.5%, respectively).
Also, individuals with ADHD group died at a higher rate than the non-ADHD group (11.57 vs 2.16 per 10,000 person-years). Not surprisingly, mortality rates were also higher among those with psychiatric disorders than for those without, as well as being higher for adults versus children.
Overall, ADHD was associated with an increase in all-cause premature death (HR 3.94, 95% CI 3.51-4.43), and the risk increased along with the age at which individuals were diagnosed, the authors reported.
The most common cause of death was "unnatural causes" (81.6%), primarily unintentional injury (35.8%) and suicide (31.4%). Meanwhile, the rates of the most common natural causes of death -- like neoplasms (3.5%) and nervous system diseases (2.8%) -- remained low.
Sun said the study is limited because the primary findings regarding psychiatric comorbidities and mortality risk were taken from adults ages 18 to 31. The observational study also relied on databases that could have misclassified ADHD diagnoses, he and his team added.
Disclosures
The study was funded by Shire International GmbH, the Swedish Research Council, the Swedish Brain Foundation, the Swedish Initiative for Research on Microdata in the Social and Medical Sciences framework, the National Institute of Mental Health, the European Union, the American Foundation for Suicide Prevention, the Aarhus University Research Foundation, the Lundbeck Foundation, the National Institutes of Health, and the Novo Nordisk Foundation.
Sun received fees from the China Scholarship Council.
Primary Source
JAMA Psychiatry
Sun S, et al "Association of psychiatric comorbidity with the risk of premature death among children and adults with attention-deficit/hyperactivity disorder" JAMA Psychiatry2019; DOI: 10.1001/jamapsychiatry.2019.1944.