Association of Psychiatric Comorbidity With the Risk of Premature Death Among Children and Adults With Attention-Deficit/Hyperactivity Disorder | Attention Deficit/Hyperactivity Disorders | JAMA Psychiatry | JAMA Network
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Faraone  SV, Asherson  P, Banaschewski  T,  et al.  Attention-deficit/hyperactivity disorder.  Nat Rev Dis Primers. 2015;1:15020. doi:10.1038/nrdp.2015.20PubMedGoogle ScholarCrossref
Biederman  J, Faraone  SV, Spencer  T,  et al.  Patterns of psychiatric comorbidity, cognition, and psychosocial functioning in adults with attention deficit hyperactivity disorder.  Am J Psychiatry. 1993;150(12):1792-1798. doi:10.1176/ajp.150.12.1792PubMedGoogle ScholarCrossref
Biederman  J, Faraone  SV.  The effects of attention-deficit/hyperactivity disorder on employment and household income.  MedGenMed. 2006;8(3):12.PubMedGoogle Scholar
Danckaerts  M, Sonuga-Barke  EJS, Banaschewski  T,  et al.  The quality of life of children with attention deficit/hyperactivity disorder: a systematic review.  Eur Child Adolesc Psychiatry. 2010;19(2):83-105. doi:10.1007/s00787-009-0046-3PubMedGoogle ScholarCrossref
Dalsgaard  S, Mortensen  PB, Frydenberg  M, Thomsen  PH.  Conduct problems, gender and adult psychiatric outcome of children with attention-deficit hyperactivity disorder.  Br J Psychiatry. 2002;181:416-421. doi:10.1192/bjp.181.5.416PubMedGoogle ScholarCrossref
Erskine  HE, Norman  RE, Ferrari  AJ,  et al.  Long-term outcomes of attention-deficit/hyperactivity disorder and conduct disorder: a systematic review and meta-analysis.  J Am Acad Child Adolesc Psychiatry. 2016;55(10):841-850. doi:10.1016/j.jaac.2016.06.016PubMedGoogle ScholarCrossref
Capusan  AJ, Bendtsen  P, Marteinsdottir  I, Larsson  H.  Comorbidity of adult ADHD and its subtypes with substance use disorder in a large population-based epidemiological study  [published online February 2, 2016].  J Atten Disord. doi:10.1177/1087054715626511PubMedGoogle Scholar
Groenman  AP, Oosterlaan  J, Rommelse  N,  et al.  Substance use disorders in adolescents with attention deficit hyperactivity disorder: a 4-year follow-up study.  Addiction. 2013;108(8):1503-1511. doi:10.1111/add.12188PubMedGoogle ScholarCrossref
Dalsgaard  S, Mortensen  PB, Frydenberg  M, Thomsen  PH.  ADHD, stimulant treatment in childhood and subsequent substance abuse in adulthood: a naturalistic long-term follow-up study.  Addict Behav. 2014;39(1):325-328. doi:10.1016/j.addbeh.2013.09.002PubMedGoogle ScholarCrossref
Chang  Z, Lichtenstein  P, D’Onofrio  BM, Sjölander  A, Larsson  H.  Serious transport accidents in adults with attention-deficit/hyperactivity disorder and the effect of medication: a population-based study.  JAMA Psychiatry. 2014;71(3):319-325. doi:10.1001/jamapsychiatry.2013.4174PubMedGoogle ScholarCrossref
Dalsgaard  S, Leckman  JF, Mortensen  PB, Nielsen  HS, Simonsen  M.  Effect of drugs on the risk of injuries in children with attention deficit hyperactivity disorder: a prospective cohort study.  Lancet Psychiatry. 2015;2(8):702-709. doi:10.1016/S2215-0366(15)00271-0PubMedGoogle ScholarCrossref
Chronis-Tuscano  A, Molina  BSG, Pelham  WE,  et al.  Very early predictors of adolescent depression and suicide attempts in children with attention-deficit/hyperactivity disorder.  Arch Gen Psychiatry. 2010;67(10):1044-1051. doi:10.1001/archgenpsychiatry.2010.127PubMedGoogle ScholarCrossref
Impey  M, Heun  R.  Completed suicide, ideation and attempt in attention deficit hyperactivity disorder.  Acta Psychiatr Scand. 2012;125(2):93-102. doi:10.1111/j.1600-0447.2011.01798.xPubMedGoogle ScholarCrossref
James  A, Lai  FH, Dahl  C.  Attention deficit hyperactivity disorder and suicide: a review of possible associations.  Acta Psychiatr Scand. 2004;110(6):408-415. doi:10.1111/j.1600-0447.2004.00384.xPubMedGoogle ScholarCrossref
Chesney  E, Goodwin  GM, Fazel  S.  Risks of all-cause and suicide mortality in mental disorders: a meta-review.  World Psychiatry. 2014;13(2):153-160. doi:10.1002/wps.20128PubMedGoogle ScholarCrossref
Dalsgaard  S, Østergaard  SD, Leckman  JF, Mortensen  PB, Pedersen  MG.  Mortality in children, adolescents, and adults with attention deficit hyperactivity disorder: a nationwide cohort study.  Lancet. 2015;385(9983):2190-2196. doi:10.1016/S0140-6736(14)61684-6PubMedGoogle ScholarCrossref
Ghirardi  L, Brikell  I, Kuja-Halkola  R,  et al.  The familial co-aggregation of ASD and ADHD: a register-based cohort study.  Mol Psychiatry. 2018;23(2):257-262. doi:10.1038/mp.2017.17PubMedGoogle ScholarCrossref
Faraone  SV, Ghirardi  L, Kuja-Halkola  R, Lichtenstein  P, Larsson  H.  The familial co-aggregation of attention-deficit/hyperactivity disorder and intellectual disability: a register-based family study.  J Am Acad Child Adolesc Psychiatry. 2017;56(2):167-174.e1. doi:10.1016/j.jaac.2016.11.011PubMedGoogle ScholarCrossref
Daviss  WB.  A review of co-morbid depression in pediatric ADHD: etiology, phenomenology, and treatment.  J Child Adolesc Psychopharmacol. 2008;18(6):565-571. doi:10.1089/cap.2008.032PubMedGoogle ScholarCrossref
Larochette  A, Bowie  CR, Harrison  AG.  Comorbid ADHD and depression in adults: additive effects on neurocognition.  Arch Clin Neuropsychol. 2009;24(5):510.Google Scholar
Mayes  SD, Calhoun  SL, Bixler  EO,  et al.  ADHD subtypes and comorbid anxiety, depression, and oppositional-defiant disorder: differences in sleep problems.  J Pediatr Psychol. 2009;34(3):328-337. doi:10.1093/jpepsy/jsn083PubMedGoogle ScholarCrossref
Cortese  S, Bernardina  BD, Mouren  MC.  Attention-deficit/hyperactivity disorder (ADHD) and binge eating.  Nutr Rev. 2007;65(9):404-411. doi:10.1111/j.1753-4887.2007.tb00318.xPubMedGoogle ScholarCrossref
Kaisari  P, Dourish  CT, Higgs  S.  Attention deficit hyperactivity disorder (ADHD) and disordered eating behaviour: a systematic review and a framework for future research.  Clin Psychol Rev. 2017;53:109-121. doi:10.1016/j.cpr.2017.03.002PubMedGoogle ScholarCrossref
Ottosen  C, Larsen  JT, Faraone  SV,  et al.  Sex differences in comorbidity patterns of attention-deficit/hyperactivity disorder.  J Am Acad Child Adolesc Psychiatry. 2019;58(4):412-422.e3. doi:10.1016/j.jaac.2018.07.910PubMedGoogle ScholarCrossref
London  AS, Landes  SD.  Attention deficit hyperactivity disorder and adult mortality.  Prev Med. 2016;90:8-10. doi:10.1016/j.ypmed.2016.06.021PubMedGoogle ScholarCrossref
Chen  YY, Chen  YL, Gau  SSF.  Attention-deficit hyperactivity disorder and suicidality: the mediating effects of psychiatric comorbidities and family function.  J Affect Disord. 2019;242:96-104. doi:10.1016/j.jad.2018.08.023PubMedGoogle ScholarCrossref
Vaa  T.  ADHD and relative risk of accidents in road traffic: a meta-analysis.  Accid Anal Prev. 2014;62:415-425. doi:10.1016/j.aap.2013.10.003PubMedGoogle ScholarCrossref
Faraone  SV.  Attention deficit hyperactivity disorder and premature death.  Lancet. 2015;385(9983):2132-2133. doi:10.1016/S0140-6736(14)61822-5PubMedGoogle ScholarCrossref
Tyrer  F, McGrother  C.  Cause-specific mortality and death certificate reporting in adults with moderate to profound intellectual disability.  J Intellect Disabil Res. 2009;53(11):898-904. doi:10.1111/j.1365-2788.2009.01201.xPubMedGoogle ScholarCrossref
Janicki  MP, Dalton  AJ, Henderson  CM, Davidson  PW.  Mortality and morbidity among older adults with intellectual disability: health services considerations.  Disabil Rehabil. 1999;21(5-6):284-294. doi:10.1080/096382899297710PubMedGoogle ScholarCrossref
Pridmore  S, Auchincloss  S.  Preventing suicide: a global imperative.  Australas Psychiatry. 2015;23(1):81-82. doi:10.1177/1039856214562079PubMedGoogle ScholarCrossref
American Psychiatric Association.  Diagnostic and Statistical Manual of Mental Disorders. 5th ed. Arlington, VA: American Psychiatric Association; 2013.
Cortese  S, Adamo  N, Del Giovane  C,  et al.  Comparative efficacy and tolerability of medications for attention-deficit hyperactivity disorder in children, adolescents, and adults: a systematic review and network meta-analysis.  Lancet Psychiatry. 2018;5(9):727-738. doi:10.1016/S2215-0366(18)30269-4PubMedGoogle ScholarCrossref
Chang  Z, Quinn  PD, Hur  K,  et al.  Association between medication use for attention-deficit/hyperactivity disorder and risk of motor vehicle crashes.  JAMA Psychiatry. 2017;74(6):597-603. doi:10.1001/jamapsychiatry.2017.0659PubMedGoogle ScholarCrossref
Quinn  PD, Chang  Z, Hur  K,  et al.  ADHD medication and substance-related problems.  Am J Psychiatry. 2017;174(9):877-885. doi:10.1176/appi.ajp.2017.16060686PubMedGoogle ScholarCrossref
Chang  Z, D’Onofrio  BM, Quinn  PD, Lichtenstein  P, Larsson  H.  Medication for attention-deficit/hyperactivity disorder and risk for depression: a nationwide longitudinal cohort study.  Biol Psychiatry. 2016;80(12):916-922. doi:10.1016/j.biopsych.2016.02.018PubMedGoogle ScholarCrossref
Chang  Z, Lichtenstein  P, Halldner  L,  et al.  Stimulant ADHD medication and risk for substance abuse.  J Child Psychol Psychiatry. 2014;55(8):878-885. doi:10.1111/jcpp.12164PubMedGoogle ScholarCrossref
Lichtenstein  P, Halldner  L, Zetterqvist  J,  et al.  Medication for attention deficit-hyperactivity disorder and criminality.  N Engl J Med. 2012;367(21):2006-2014. doi:10.1056/NEJMoa1203241PubMedGoogle ScholarCrossref
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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. 2019;76(11):1141-1149. 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.


    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.