In adults with attention-deficit/hyperactivity disorder (ADHD) the presence of a comorbid psychiatric disorder increases the risk for premature death, according to Swedish study results published in JAMA Psychiatry. Whereas early-onset psychiatric comorbidity was primarily associated with increased risk for natural death, later-onset psychiatric comorbidity was more often associated with death due to unnatural causes, including suicide and unintentional injury.

A Danish study found a 2-fold increase in the risk for all-cause mortality in ADHD, with unintentional injury as the leading cause of death. However, the study did not explore the role of comorbid psychiatric disorders.

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Shihua Sun, MD, of the Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden, and colleagues conducted a prospective cohort study using Swedish national registers to identify 2,675,615 individuals born between 1983 and 2009 in Sweden for inclusion in the study. In the cohort, 86,670 individuals had received a diagnosis of ADHD. In this population the investigators identified all-cause and cause-specific mortality as the main outcomes.

During the follow-up period, 424 individuals with ADHD and 6231 without ADHD died, which translates to mortality rates of 11.57 and 2.16 per 10,000 person-years, respectively. The hazard ratio (HR) in adults with ADHD was 4.64 compared with an HR of 1.41 for children. The risk for mortality increased in a dose-response fashion with the number of psychiatric comorbidities. Of patients with 1 comorbidity the HR was 3.71, whereas with 4 or more psychiatric comorbidities, the HR was 25.22. The comorbidity with the highest risk for mortality was schizophrenia, with a mortality rate per 10,000 person-years of 112.20, followed by substance use disorder (SUD) (79.41), bipolar disorder (55.99), anxiety disorder (51.10), and depression (39.74) as compared with a rate of 5.54 for ADHD alone. Except for autism spectrum disorder, most of these comorbid disorders were associated with increased risk for all-cause mortality in individuals with ADHD. The strongest association was found for SUD, with an adjusted HR of 8.01.

In adults, early-onset psychiatric comorbidity contributed substantially to the premature mortality risks due to natural causes. Comparatively, later-onset psychiatric comorbidity, especially SUD, was associated with a substantial part of the risk for unnatural deaths, including most of the deaths due to unintentional injuries and all suicide deaths.

The study relied on clinical diagnoses and prescriptions to identify individuals with ADHD, which could have led to false-positive misclassification in some cases; missed diagnoses may have occurred as well.

“These results suggest that overall health conditions and risk of psychiatric comorbidity should be evaluated clinically to identify high-risk groups among individuals with ADHD,” the investigators included.

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.

Reference

Sun S, Kuja-Halkola R, Faraone SV, et al. Association of psychiatric comorbidity with the risk of premature death among children and adults with attention-deficit/hyperactivity disorder [published online August 7, 2019]. JAMA Psychiatry.doi:10.1001/jamapsychiatry.2019.1944