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Original Investigation
August 7, 2019

Association of Psychiatric Comorbidity With the Risk of Premature Death Among Children and Adults With Attention-Deficit/Hyperactivity Disorder

Author Affiliations
  • 1Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
  • 2Department of Psychiatry, State University of New York (SUNY) Upstate Medical University, Syracuse
  • 3Department of Neuroscience and Physiology, SUNY Upstate Medical University, Syracuse
  • 4Department of Psychological and Brain Sciences, Indiana University, Bloomington
  • 5National Centre for Register-Based Research, Department of Economics and Business Economics, Aarhus University, Aarhus, Denmark
  • 6iPSYCH–The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus, Denmark
  • 7Department for Child and Adolescent Psychiatry, Hospital of Telemark, Kragerø, Norway
  • 8School of Medical Sciences, Örebro University, Örebro, Sweden
JAMA Psychiatry. Published online August 7, 2019. doi:10.1001/jamapsychiatry.2019.1944
Key Points

Question  Is attention-deficit/hyperactivity disorder (ADHD) associated with premature death, and what is the role of psychiatric comorbidity?

Findings  This cohort study of Swedish register data of 86 670 individuals with ADHD found that ADHD was associated with elevated risk of premature death, and psychiatric comorbidity played an important role for the all-cause and cause-specific associations in adults. Early-onset psychiatric comorbidity was mainly associated with the risk of natural deaths whereas later-onset psychiatric comorbidity was mainly associated with death due to unnatural causes, including suicide and unintentional injury.

Meaning  These findings suggest that health care professionals should closely monitor specific psychiatric comorbidities in individuals with ADHD to identify high-risk groups and implement prevention efforts.

Abstract

Importance  A previous register-based study reported elevated all-cause mortality in attention-deficit/hyperactivity disorder (ADHD), but cause-specific risks and the potential associations of psychiatric comorbidities remain unknown.

Objectives  To investigate the all-cause and cause-specific mortality risks in ADHD and to explore the potential role of psychiatric comorbidities.

Design, Setting, and Participants  This prospective cohort study used Swedish national registers to identify 2 675 615 individuals born in Sweden from January 1, 1983, through December 31, 2009, as the study population, among whom 86 670 individuals (3.2%) received a diagnosis of ADHD during follow-up. Follow-up was completed December 31, 2013, and data were analyzed from October 2018 through March 2019.

Exposures  Attention-deficit/hyperactivity disorder identified by first clinical diagnosis or first prescription of ADHD medications as recorded in Swedish registers. Clinical diagnosis of psychiatric comorbidity was available in the National Patient Register.

Main Outcomes and Measures  All-cause and cause-specific mortalities and hazard ratios (HRs) using Cox proportional hazards regression models.

Results  In the overall cohort of 2 675 615 individuals, 1 374 790 (51.4%) were male (57 919 with an ADHD diagnosis) and 1 300 825 (48.6%) were female (28 751 with an ADHD diagnosis). Mean (SD) age at study entry was 6.4 (5.6) years. During follow-up, 424 individuals with ADHD and 6231 without ADHD died, resulting in mortality rates of 11.57 and 2.16 per 10 000 person-years, respectively. The association was stronger in adulthood (HR, 4.64; 95% CI, 4.11-5.25) compared with childhood (HR, 1.41; 95% CI, 0.97-2.04) and increased substantially with the number of psychiatric comorbidities with ADHD (HR for individuals with only ADHD, 1.41 [95% CI, 1.01-1.97]; HR for those with ≥4 comorbidities, 25.22 [95% CI, 19.60-32.46]). In adulthood, when adjusting for early-onset psychiatric comorbidity, the association between ADHD and risk of death due to natural causes was attenuated substantially and was no longer statistically significant (HR, 1.32; 95% CI, 0.94-1.85). When adjusting for later-onset psychiatric disorders, the association was attenuated to statistical nonsignificance for death due to suicide (HR, 1.13; 95% CI, 0.88-1.45) but remained statistically significant for death caused by unintentional injury (HR, 2.14; 95% CI, 1.71-2.68) or other external causes (HR, 1.75; 95% CI, 1.23-2.48).

Conclusions and Relevance  Psychiatric comorbidity appears to play an important role in all-cause and cause-specific mortality risks in ADHD. In adulthood, early-onset psychiatric comorbidity contributed primarily to the association with death due to natural causes, whereas later-onset psychiatric comorbidity mainly influenced death due to unnatural causes, including suicide and unintentional injury. These findings suggest that health care professionals should closely monitor specific psychiatric comorbidities in individuals with ADHD to identify high-risk groups for prevention efforts.

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