Elsevier

The Lancet

Volume 385, Issue 9983, 30 May–5 June 2015, Pages 2190-2196
The Lancet

Articles
Mortality in children, adolescents, and adults with attention deficit hyperactivity disorder: a nationwide cohort study

https://doi.org/10.1016/S0140-6736(14)61684-6Get rights and content

Summary

Background

Attention deficit hyperactivity disorder (ADHD) is a common mental disorder associated with factors that are likely to increase mortality, such as oppositional defiant disorder or conduct disorder, criminality, accidents, and substance misuse. However, whether ADHD itself is associated with increased mortality remains unknown. We aimed to assess ADHD-related mortality in a large cohort of Danish individuals.

Methods

By use of the Danish national registers, we followed up 1·92 million individuals, including 32 061 with ADHD, from their first birthday through to 2013. We estimated mortality rate ratios (MRRs), adjusted for calendar year, age, sex, family history of psychiatric disorders, maternal and paternal age, and parental educational and employment status, by Poisson regression, to compare individuals with and without ADHD.

Findings

During follow-up (24·9 million person-years), 5580 cohort members died. The mortality rate per 10 000 person-years was 5·85 among individuals with ADHD compared with 2·21 in those without (corresponding to a fully adjusted MRR of 2·07, 95% CI 1·70–2·50; p<0·0001). Accidents were the most common cause of death. Compared with individuals without ADHD, the fully adjusted MRR for individuals diagnosed with ADHD at ages younger than 6 years was 1·86 (95% CI 0·93–3·27), and it was 1·58 (1·21–2·03) for those aged 6–17 years, and 4·25 (3·05–5·78) for those aged 18 years or older. After exclusion of individuals with oppositional defiant disorder, conduct disorder, and substance use disorder, ADHD remained associated with increased mortality (fully adjusted MRR 1·50, 1·11–1·98), and was higher in girls and women (2·85, 1·56–4·71) than in boys and men (1·27, 0·89–1·76).

Interpretation

ADHD was associated with significantly increased mortality rates. People diagnosed with ADHD in adulthood had a higher MRR than did those diagnosed in childhood and adolescence. Comorbid oppositional defiant disorder, conduct disorder, and substance use disorder increased the MRR even further. However, when adjusted for these comorbidities, ADHD remained associated with excess mortality, with higher MRRs in girls and women with ADHD than in boys and men with ADHD. The excess mortality in ADHD was mainly driven by deaths from unnatural causes, especially accidents.

Funding

This study was supported by a grant from the Lundbeck Foundation.

Introduction

Many mental disorders are associated with shortened life expectancy,1 but little is known about whether this association occurs for attention deficit hyperactivity disorder (ADHD). However, ADHD is known to be associated with several factors that are likely to affect mortality rates. In the USA and Europe, the most common cause of death in childhood is unintentional injury,2 and children with ADHD have an increased risk of sustaining injuries.3 Similarly, adults with ADHD are at increased risk of serious traffic accidents.4 ADHD is also associated with substance use disorder,5 criminality,6, 7, 8 and development of more severe mental disorders,9, 10 which might affect life expectancy. Comorbid oppositional defiant disorder and conduct disorder have previously been shown to be among the strongest and most negative prognostics in children and adolescents with ADHD, significantly increasing the risk of later development of psychotic disorders11 and substance use disorder,5 and risk of committing crime.6

Thus, many reasons exist to believe that ADHD is associated with increased risk of early death. However, to our knowledge, only one study12 has compared the mortality of individuals with ADHD with that of population controls. The results suggested increased mortality among 367 individuals with ADHD (standardised mortality ratio 1·88, 95% CI 0·83–4·26, p=0·13), which we believe did not reach significance because of statistical power limitations.12 Whether ADHD is associated with increased mortality therefore remains unknown.

To compare the risk of a rare event, such as premature death, in individuals with ADHD with healthy controls, a large sample size with long follow-up is needed. The longitudinal Danish registers offer such an opportunity.13, 14, 15, 16 In the present prospective follow-up study of a nationwide birth cohort, we aimed to estimate excess all-cause mortality in children, adolescents, and adults with ADHD. Additionally, we examined the added effect of comorbid oppositional defiant disorder, conduct disorder, and substance use disorder on mortality rates in individuals with ADHD.

Section snippets

Study population

All people living in Denmark from 1968 onwards are registered in The Danish Civil registration System.16 For each person registered, the system includes a ten-digit personal identification number (PIN) and information on sex, date and place of birth, vital status (continuously updated), and parents' personal identifiers. The PIN is used in all national registers, enabling accurate linkage of data between registers at an individual level. Our study cohort included all children born in Denmark

Results

We followed up 1 922 248 individuals up to a maximum age of 32 years, from their first birthdays or Jan 1, 1995 (whichever came last) until death, emigration from Denmark, or June 30, 2013 (whichever came first). We included 24 907 560 person-years in the study. In 44 883 (2·3%) children and adolescents, follow-up was ended before the end of the study (June 30, 2013) because of emigration from Denmark (44 009 individuals) or because they were lost to follow-up (874 individuals). During

Discussion

In this nationwide prospective cohort study with up to 32 year follow-up, children, adolescents, and adults with ADHD had decreased life expectancy and more than double the risk of death compared with people without ADHD. The risk seemed to be highest within the first 5 years of diagnosis of ADHD (crude MRRs 2·45–3·75), but even after more than 10 years, the mortality rate was still almost doubled (1·9). Additionally, mortality rate significantly depended on age at first ADHD diagnosis. People

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