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Articles   |    
Comprehensive Meta-Analysis of Excess Mortality in Depression in the General Community Versus Patients With Specific Illnesses
Pim Cuijpers, Ph.D.; Nicole Vogelzangs, Ph.D.; Jos Twisk, Ph.D.; Annet Kleiboer, Ph.D.; Juan Li, Ph.D.; Brenda W. Penninx, Ph.D.
Am J Psychiatry 2014;171:453-462. doi:10.1176/appi.ajp.2013.13030325
View Author and Article Information

The authors report no financial relationships with commercial interests.

From the Department of Clinical Psychology, VU University Amsterdam, the Netherlands; the Department of Psychiatry, VU University Medical Center, Amsterdam; the EMGO Institute for Health and Care Research, Amsterdam; and the Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing.

Address correspondence to Dr. Cuijpers (p.cuijpers@vu.nl).

Copyright © 2014 by the American Psychiatric Association

Received March 19, 2013; Revised October 12, 2013; Accepted November 18, 2013.

Abstract

Objective  Several hundred studies have shown that depression is associated with an elevated risk of dying at follow-up. It is not clear, however, whether the mechanisms for this association are disease specific, leading to higher mortality in specific patient groups, or generic, resulting in comparable mortality rates in all patient groups as well as in community samples. The authors conducted a comprehensive meta-analysis of prospective studies of community as well as patient samples associating depression at baseline with excess mortality at follow-up.

Method  The authors conducted systematic searches of PubMed, PsycINFO, and Embase. Studies were included if depression was measured with a standardized instrument and mortality was reported for both depressed and nondepressed participants at follow-up.

Results  A total of 293 studies including 1,813,733 participants (135,007 depressed and 1,678,726 nondepressed) from 35 countries were included. The overall unadjusted relative risk of mortality in depressed relative to nondepressed participants was 1.64 (95% CI=1.56–1.76), with high heterogeneity (I2=83, 95% CI=80–84). After adjustment for publication bias, the overall relative risk was reduced to 1.52 (95% CI=1.45–1.59). No strong indications were found that the pooled relative risk was different across the relatively healthy community samples and specific patient samples with heart disease, cancer, kidney disease, or other disease, except for a significantly higher risk in patients with chronic obstructive pulmonary disease (p<0.05). Also, the relative risk was lower when the follow-up period was longer and when the quality of the study was higher.

Conclusions  The authors could confirm the presence of a significant association between depression and excess mortality, although this association may have been overestimated because of publication bias and low study quality. Few indications were found that this association is stronger in community or specific patient samples.

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FIGURE 1. Flowchart of Inclusion of Studies in a Meta-Analysis of Excess Mortality in Depression in Community and Patient Studies

FIGURE 2. Funnel Plot of Standard Error by Log Relative Risk of Excess Mortality in Adult Depression: Actual and Imputed Studiesa

a The white circles indicate actual studies, and the green circles indicate the imputed studies—those that would have been there if the funnel plot had been symmetrical. The vertical line represents the pooled log relative risk after adjustment for publication bias. The diagonal lines represent the borders of the funnel plot.

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TABLE 1.Selected Characteristics of Studies Examining the Association Between Depression and Excess Mortality
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a These were studies of patients with mixed diagnoses admitted to a hospital or to specific wards or units of a hospital; mixed populations from inpatient settings (e.g., frail elderly patients; veterans); and mixed patient groups from outpatient clinics.

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b In the other patient groups category, we grouped studies of patients with cirrhosis, Parkinson’s disease, rheumatoid arthritis, liver transplantation, spinal cord injury, or hypertension; patients being weaned from prolonged mechanical ventilation; and elderly patients discharged from a rehabilitation ward after orthopedic surgery on a lower limb.

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TABLE 2.Unadjusted Relative Risk of Excess Mortality in Depressed Compared With Nondepressed Participantsa
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a Hazard ratios and odds ratios were treated as if they were relative risks.

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b The p value here indicates whether the Q statistic was significant.

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c Studies with a relative risk ≥4 or <0.25 were considered to be outliers.

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d In the other patient groups category, we grouped the following studies together: patients with cirrhosis, dementia, hip fracture/surgery, HIV, liver transplantation, Parkinson’s disease; patients being weaned from prolonged mechanical ventilation; and elderly patients discharged from a rehabilitation ward after orthopedic surgery on a lower limb.

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e Three studies for which the follow-up period was not clear were excluded from these analyses.

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* p<0.05. **p<0.01. ***p<0.001.

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TABLE 3.Multivariate Meta-Regression Analyses of Study Characteristics and Effect Sizes
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a In the parsimonious model, the least significant variable was dropped in each step of a backward regression analysis, until only significant predictors (p<0.05) were retained.

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b Entered in the model as continuous variables.

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TABLE 4.Adjusted Relative Risk of Excess Mortality in Depressed Compared With Nondepressed Participantsa
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a When there were five or fewer studies in one subgroup these were clustered together in the category “other somatic illness.”

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b The asterisks in the I2 column indicate the significance level of the Q statistic.

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c This p value indicates whether the effect sizes in the subgroups differ significantly from each other.

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d Only two of the 11 studies were patient samples; we considered this subgroup too small to conduct subgroup analyses. Lifestyle factors include variables such as smoking, body mass index, exercise, and alcohol use.

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e Illness-related factors include illness-related variables indicating the severity of a disorder and the presence and severity of comorbid disorders.

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*p<0.05. **p<0.01. ***p<0.001.

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