The association of unipolar depression with thirty-day mortality after hospitalization for infection: A population-based cohort study in Denmark

https://doi.org/10.1016/j.jpsychores.2016.08.006Get rights and content

Highlights

  • We studied if depression raised risk of 30-day mortality after serious infection.

  • Depression raised risk of 30-day mortality after serious infection slightly.

  • Persons starting antidepressants within a year pre-infection were at greatest risk.

Abstract

Objective

While depression is associated with higher risk of death due to chronic medical conditions, it is unknown if depression increases mortality following serious infections. We sought to determine if pre-existing unipolar depression is associated with increased mortality within 30 days after hospitalization for a serious infection.

Methods

We conducted a population-based cohort study of all adults hospitalized for an infection in Denmark between 2005 and 2013. Pre-existing unipolar depression was ascertained via psychiatrist diagnoses or at least two antidepressant prescription redemptions within a six month period. Our primary outcome was all-cause mortality within 30 days after infection-related hospitalization. We also studied death due to infection within 30 days after admission.

Results

We identified 589,688 individuals who had a total of 703,158 hospitalizations for infections. After adjusting for demographics, infectious diagnosis and time since infection, socioeconomic factors and comorbidities, pre-existing unipolar depression was associated with slightly increased risk of all-cause mortality within 30 days after infection-related hospitalization (Mortality Rate Ratio [MRR]: 1.07, 95% Confidence Interval [95% CI]: 1.05, 1.09). The association was strongest among persons who initiated antidepressant treatment within one year before the infection (MRR: 1.30, 95% CI: 1.25, 1.35). Pre-existing unipolar depression was associated with increased risk of death due to sepsis (MRR: 1.30, 95% CI: 1.17, 1.44), pneumonia (MRR: 1.23, 95% CI: 1.16, 1.29) and urinary tract infection (MRR: 1.25, 95% CI: 1.08, 1.44) after adjusting for demographics, infectious diagnosis at admission and time since infection.

Conclusions

Pre-existing unipolar depression is associated with slightly increased mortality following hospitalization for an infection.

Introduction

Depression is a highly prevalent psychiatric disorder throughout the world [1]. It is a leading cause of years lived with disability [1], and individuals with depression suffer more chronic medical disease-related sequelae than those without depression [2]. Notably, a recent meta-analysis identified that having a diagnosis of depression is associated with a 71% greater risk for premature all-cause mortality [3]. Importantly, a nationwide cohort study from Denmark identified that unipolar depression is associated with a decreased life expectancy of 14 years in men and 10 years in women [4]. While this study found that depression was strongly associated with increased risk for death due to suicide and accidents [4], the absolute number of deaths attributable to depression was highest for medical diseases [4].

Yet, while depression is known to be associated with increased risk for mortality in patients with chronic diseases such as diabetes and coronary artery disease [5], [6], [7], it remains unclear whether death following acute medical illnesses may explain some of the association between depression and reduced life expectancy. Depression has been found to be associated with increased risk for hospitalization for serious infections [8], but it is unknown if pre-existing depression is a risk factor for death following serious infections. This possibility is important to consider since depression has been shown to be associated with increased levels of inflammatory cytokines [9], a contributing factor in the development of sepsis in the face of infection [10], from which nearly 1/3rd of patients do not survive [11]. Furthermore, a recent study identified that individuals with schizophrenia or bipolar disorder have higher mortality following hospitalization for an infection [12]. Since unipolar depression is more prevalent in the general population than schizophrenia or bipolar disorder [13], [14], and evidence-based depression treatments are being increasingly integrated into general practice settings world-wide [15], [16], identifying depression as a potential risk factor for death following hospitalization for a serious infection could have important public health impact.

The present study utilizes data from a large population-based cohort of Danish adults to determine if pre-existing unipolar depression is associated with increased risk of mortality within 30 days after hospitalization for a serious infection. We hypothesized that pre-existing depression would be associated with a higher relative risk of death when compared to individuals without pre-existing depression.

Section snippets

Population

We conducted a population-based cohort investigation utilizing data from nationwide Danish registries. Our cohort included all living persons aged 15 years or older, residing in Denmark for at least 10 years (to ensure continuous information on depression), and hospitalized for an infection at least once between January 1, 2005 and December 1, 2013. We constructed our cohort using information from two registries: 1) the Danish Civil Registration System [17], which includes data on sex, birth

Results

After excluding 14,709 persons with a diagnosis of schizophrenia, schizoaffective disorder or bipolar disorder and 2457 persons who died on the day of hospitalization (of whom 797 were depressed), 589,688 individuals were hospitalized a total of 703,158 times for an infection during the study period. Of the hospitalizations, 189,817 (27.0%) were among individuals with pre-existing unipolar depression. Table 1 displays the characteristics of our cohort at time of hospitalization for infection by

Discussion

In this population-based cohort study of individuals hospitalized for an infection, we found that having pre-existing unipolar depression was associated with a slightly increased risk of all-cause mortality within 30 days after admission. Notably, this association remained significant even after controlling for medical and substance use comorbidities, suggesting that our findings may be overly conservative since medical and substance use comorbidities could mediate the association of

Disclosures

The authors have no relevant conflicts of interest to disclose.

Funding

This work was supported by an unrestricted grant (grant number: R155-2012-11280) from the Lundbeck Foundation.

References (53)

  • A.H. Miller et al.

    Inflammation and its discontents: the role of cytokines in the pathophysiology of major depression

    Biol. Psychiatry

    (2009)
  • J.J. Young et al.

    A review of the relationship between proinflammatory cytokines and major depressive disorder

    J. Affect. Disord.

    (2014)
  • J. Maurer et al.

    Anxiety and depression in COPD: current understanding, unanswered questions, and research needs

    Chest

    (2008)
  • B.N. Gaynes et al.

    A direct comparison of presenting characteristics of depressed outpatients from primary vs. specialty care settings: preliminary findings from the STAR*D clinical trial

    Gen. Hosp. Psychiatry

    (2005)
  • Global, regional, and national incidence, prevalence, and years lived with disability for 301 acute and chronic diseases and injuries in 188 countries, 1990–2013: a systematic analysis of the Global Burden of Disease Study 2013

    Lancet

    (2015)
  • E.R. Walker et al.

    Mortality in mental disorders and global disease burden implications: a systematic review and meta-analysis

    JAMA Psychiatry.

    (2015)
  • W.J. Katon et al.

    The association of comorbid depression with mortality in patients with type 2 diabetes

    Diabetes Care

    (2005)
  • M.D. Sullivan et al.

    Depression predicts all-cause mortality: epidemiological evaluation from the ACCORD HRQL substudy

    Diabetes Care

    (2012)
  • F. Doyle et al.

    Systematic review and individual patient data meta-analysis of sex differences in depression and prognosis in persons with myocardial infarction: a MINDMAPS study

    Psychosom. Med.

    (2015)
  • N.W. Andersson et al.

    Depression and the risk of severe infections: prospective analyses on a nationwide representative sample

    Int. J. Epidemiol.

    (2016)
  • A.R. Ribe et al.

    Thirty-day mortality after infection among persons with severe mental illness: a population-based cohort study in Denmark

    Am. J. Psychiatry

    (2015)
  • R.C. Kessler et al.

    Lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the National Comorbidity Survey Replication

    Arch. Gen. Psychiatry

    (2005)
  • J. Perälä et al.

    Lifetime prevalence of psychotic and bipolar disorder I disorders in a general population

    Arch. Gen. Psychiatry

    (2007)
  • L.I. Solberg et al.

    A stepped-wedge evaluation of an initiative to spread the collaborative care model for depression in primary care

    Ann. Fam. Med.

    (2015)
  • J. Gensichen et al.

    Case management for depression by health care assistants in small primary care practices: a cluster randomized trial

    Ann. Intern. Med.

    (2009)
  • C.B. Pedersen

    The Danish civil registration system

    Scand. J. Publ. Health.

    (2011)
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