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The association of depression and all-cause and cause-specific mortality: an umbrella review of systematic reviews and meta-analyses

The association of depression and all-cause and cause-specific mortality: an umbrella review of systematic reviews and meta-analyses

Machado, Myrela O., Veronese, Nicola, Sanches, Marcos, Stubbs, Brendon, Koyanagi, Ai, Thompson, Trevor ORCID: 0000-0001-9880-782X, Tzoulaki, Ioanna, Solmi, Marco, Vancampfort, Davy, Schuch, Felipe B., Maes, Michael, Fava, Giovanni A., Ioannidis, John P. A. and Carvalho, André F. (2018) The association of depression and all-cause and cause-specific mortality: an umbrella review of systematic reviews and meta-analyses. BMC Medicine, 16:112. ISSN 1741-7015 (Online) (doi:

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Depression is a prevalent and disabling mental disorder that frequently co-occurs with a wide range of chronic conditions. Evidence has suggested that depression could be associated with excess all-cause mortality across different settings and populations, although the causality of these associations remains unclear.

We conducted an umbrella review of systematic reviews and meta-analyses of observational studies. PubMed, PsycINFO, and Embase electronic databases were searched through January 20, 2018. Systematic reviews and meta- analyses that investigated associations of depression and all-cause and cause-specific mortality were selected for the review. The evidence was graded as convincing, highly suggestive, suggestive, or weak based on quantitative criteria that included an assessment of heterogeneity, 95% prediction intervals, small-study effects, and excess significance bias.

A total of 26 references providing 2 systematic reviews and data for 17 meta-analytic estimates met inclusion criteria (19 of them on all-cause mortality); data from 246 unique studies (N = 3,825,380) were synthesized. All 17 associations had P < 0.05 per random effects summary effects, but none of them met criteria for convincing evidence. Associations of depression and all-cause mortality in patients after acute myocardial infarction, in individuals with heart failure, in cancer patients as well as in samples from mixed settings met criteria for highly suggestive evidence. However, none of the associations remained supported by highly suggestive evidence in sensitivity analyses that considered studies employing structured diagnostic interviews. In addition, associations of depression and all-cause mortality in cancer and post-acute myocardial infarction samples were supported only by suggestive evidence when studies that tried to adjust for potential confounders were considered.

Even though associations between depression and mortality have nominally significant results in all assessed settings and populations, the evidence becomes weaker when focusing on studies that used structured interviews and those that tried to adjust for potential confounders. A causal effect of depression on all-cause and cause-specific mortality remains unproven, and thus interventions targeting depression are not expected to result in lower mortality rates at least based on current evidence from observational studies.

Item Type: Article
Additional Information: © The Author(s). 2018 Open Access. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (, which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated.
Uncontrolled Keywords: Depression, Mortality, All-cause, Cause-specific, Systematic reviews, Meta-analyses, Survival, Umbrella review, Psychiatry
Subjects: B Philosophy. Psychology. Religion > BF Psychology
Faculty / Department / Research Group: Faculty of Education & Health
Faculty of Education & Health > Applied Psychology Research Group
Faculty of Education & Health > Department of Psychology, Social Work & Counselling
Last Modified: 25 Aug 2018 21:29
Selected for GREAT 2016: None
Selected for GREAT 2017: None
Selected for GREAT 2018: None
Selected for GREAT 2019: None

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