Cited by 703Cardiac Health and Mental HealthSuicide and Self-Harm StudiesMental Health Treatment and Access

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A Systematic Review of the Mortality of Depression

Wulsin, Lawson R., Vaillant, George E., Wells, Victoria E.·1999·Psychosomatic Medicine

DOI 10.1097/00006842-199901000-00003

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Abstract

OBJECTIVE: The literature on the mortality of depression was assessed with respect to five issues: 1) strength of evidence for increased mortality, 2) controlling for mediating factors, 3) the contribution of suicide, 4) variation across sample types, and 5) possible mechanisms. METHOD: All relevant English language databases from 1966 to 1996 were searched for reviews and studies that included 1) a formal assessment of depressive symptoms or disorders, 2) death rates or risks, and 3) an appropriate comparison group. RESULTS: There were 57 studies found; 29 (51%) were positive, 13 (23%) negative, and 15 (26%) mixed. Twenty-one studies (37%) ranked among the better studies on the strength of evidence scale used in this study, but there are too few comparable, well-controlled studies to provide a sound estimate of the mortality risk associated with depression. Only six studies controlled for more than one of the four major mediating factors. Suicide accounted for less than 20% of the deaths in psychiatric samples, and less than 1% in medical and community samples. Depression seems to increase the risk of death by cardiovascular disease, especially in men, but depression does not seem to increase the risk of death by cancer. Variability in methods prevents a more rigorous meta-analysis of risk. CONCLUSION: The studies linking depression to early death are poorly controlled, but they suggest that depression substantially increases the risk of death, especially death by unnatural causes and cardiovascular disease. Future well-controlled studies of high risk groups may guide efforts to develop treatments that reduce the mortality risk of depression.

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“The earliest of these, a review of 57 studies published between 1966 and 1996 [ 6 ] found 29 (51%) reported a positive relationship between depression and mortality.”
BackgroundResultInfluential
Association of detected depression and undetected depressive symptoms with long-term mortality in a cohort of institutionalised older people
Damián, J., Pastor‐Barriuso, R., Gama, E. V., & de Pedro‐Cuesta, J. (2016) · Epidemiology and Psychiatric Sciences · doi:10.1017/s2045796015001171 · Cited by 21
“Indeed, three systematic reviews in the general population (Wulsin et al. 1999; Cuijpers et al. 2014) and in older people (Schulz et al.”
Background
Do Antidepressants Reduce the Burden Imposed by Depression on Employers?
Greener, M., & Guest, J. F. (2005) · CNS Drugs · doi:10.2165/00023210-200519030-00006 · Cited by 22
Psychoneuroimmunology of Depressive Disorder: Mechanisms and Clinical Implications
Capuron, L., Miller, A. H., & Irwin, M. R. (2007) · Elsevier eBooks · doi:10.1016/b978-012088576-3/50030-7 · Cited by 22
A framework for describing the impact of antidepressant medications on population health status
Patten, S. B. (2002) · Pharmacoepidemiology and Drug Safety · doi:10.1002/pds.746 · Cited by 21
“Based on NCS,28 see text for explanation MRH Age-specific mortality See below: (a) Polynomial regression rate in H (per month) model fit to Canadian age-specific mortality rates MH Age-specific mortality See below: (b) in H, per month MRD Mortality in Dxj MRH 1.7 Based on review by Wulsin et al.4 MDxy Deaths in the de…”
BackgroundInfluential
Clinical depression and anxiety among ST-elevation myocardial infarction hospitalizations: Results from Nationwide Inpatient Sample 2004–2013
Pino, E. C., Zuo, Y., Borba, C. P. C., Henderson, D. C., & Kalesan, B. (2018) · Psychiatry Research · doi:10.1016/j.psychres.2018.03.025 · Cited by 20
“In contrast to obesity, both smoking and chronic disease states are associated with increased levels of both depression and mortality (Wulsin et al., 1999; Barth et al., 2004).”
Depression and cause-specific mortality in an ethnically diverse cohort from the UK: 8-year prospective study
Das‐Munshi, J., Chang, C., Schofield, P., Stewart, R. J., & Prince, M. J. (2018) · Psychological Medicine · doi:10.1017/s0033291718002210 · Cited by 23
“The finding of an increased mortality risk in people with depression is consistent with the literature (Wulsin et al., 1999; Saz and Dewey, 2001; Cuijpers et al., 2014).”
BackgroundResult
Depression in patients with chronic kidney disease on dialysis in Saudi Arabia
Zaben, F. A., Khalifa, D. A., Sehlo, M. G., Shohaib, S. A., Shaheen, F., Alhozali, H. M., Hariri, A. O., Ahmad, R. G., Kabli, M. R., & Koenig, H. G. (2014) · International Urology and Nephrology · doi:10.1007/s11255-014-0802-2 · Cited by 20
“Depression is a potent risk factor for disease morbidity, as medical patients with DD have double the mortality of non-depressed persons [8, 9].”
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Effects of Antidepressants on IP-10 Production in LPS-Activated THP-1 Human Monocytes
Tsai, J., Kuo, C., Yang, P., Cheng, K., Wang, P., Chen, C., & Hung, C. (2014) · International Journal of Molecular Sciences · doi:10.3390/ijms150813223 · Cited by 21
“MDD and CVD frequently occur together, and result in increased cardiovascular mortality [4–7].”
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Depression: A Quiet Killer by Any Name
Peyrot, M. F. (2003) · Diabetes Care · doi:10.2337/diacare.26.10.2952 · Cited by 20
Depression and mortality in a high-risk population
Abas, M., Hotopf, M. H., & Prince, M. J. (2002) · The British Journal of Psychiatry · doi:10.1017/s0007125000161835 · Cited by 20
Early-life exposure to famine and late-life depression: Does leukocyte telomere length mediate the association?
He, S., Li, J., Wang, Z., Wang, L., Liu, L., Sun, X., Shohaib, S. A., & Koenig, H. G. (2020) · Journal of Affective Disorders · doi:10.1016/j.jad.2020.05.082 · Cited by 19
A Review of Lifetime Risk Factors for Mortality
Kuh, D. J., Hardy, R., Hotopf, M. H., Lawlor, D. A., Maughan, B., Westendorp, R., Cooper, R., Black, S., & Mishra, G. D. (2009) · British Actuarial Journal · doi:10.1017/s135732170000550x · Cited by 19
“Adult cognition has also been shown to be a risk factor for physical chronic diseases, including CVD (Hemmingsson et al., 2007; Kuh et al., 2009a).”
BackgroundInfluential
Healthy Options: study protocol and baseline characteristics for a cluster randomized controlled trial of group psychotherapy for perinatal women living with HIV and depression in Tanzania
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Brain stimulation therapies for neuropsychiatric disease
Holtzheimer, P. E., Kosel, M., & Schlaepfer, T. E. (2012) · Handbook of clinical neurology · doi:10.1016/b978-0-444-52002-9.00041-3 · Cited by 19
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Franch, J. V., Pujol, X. P., Pousa, S. L., Reglà, J. L., Merino‐Aguado, J., & Garre‐Olmo, J. (2011) · International Journal of Geriatric Psychiatry · doi:10.1002/gps.2691 · Cited by 19
“Even though the majority of studies highlight the relationship between depression and mortality in all age groups, around a quarter of these studies have shown negative results (Wulsin et al., 1999; Schultz et al., 2002).”
BackgroundResultInfluential
Depression & Dispiritedness in Later Life
Butcher, H. K., & McGonigal-Kenney, M. L. (2005) · AJN American Journal of Nursing · doi:10.1097/00000446-200512000-00032 · Cited by 19
Street Music or the Blues? The Lived Experience and Social Environment of Depression
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Veränderung der Häufigkeit suizidaler Handlungen nach zwei Jahren „Bündnis gegen Depression“
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Mortality of subjects with mood disorders in the Lundby community cohort: A follow-up over 50 years
Mattisson, C., Bogren, M., Brådvik, L., & Horstmann, V. (2015) · Journal of Affective Disorders · doi:10.1016/j.jad.2015.02.028 · Cited by 19
“A review using a systematic method by Wulsin et al. (1999) showed that depression is associated with an increased mortality.”
Method
Acid-Producing Diet and Depressive Symptoms among Breast Cancer Survivors: A Longitudinal Study
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“Depression is common in cancer survivors and can significantly reduce their quality of life and increase all-cause mortality [2,3].”
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Andersen, N. K., Wimmelmann, C. L., Mortensen, E. L., & Flensborg‐Madsen, T. (2021) · Journal of Psychosomatic Research · doi:10.1016/j.jpsychores.2021.110529 · Cited by 18
Cognitive behavioural therapy for the treatment of depression in Christian patients with medical illness
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“Depression is associated with higher rates of morbidity, mortality, and medical costs (Koenig, Shelp, Goli, Cohen, & Blazer, 1989 ), especially among those with a medical illness whose risk of mortality is twice that of the general population (Koenig et al, 1989 ; Wulsin, Vailant, & Wells, 1999 ).”
Background
Psychological and social resources relate to biomarkers of allostasis in newly admitted nursing home residents
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DEPRESIÓN EN ANCIANOS
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“Depression is associated with an increased risk of mortality which is primarily related to increased cardiovascular death (Anstey and Luszcz, 2002; Wulsin et al., 1999).”
Background
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“8% (Goodwin and Jamison, 2007; Lönnqvist, 2000; Wulsin et al., 1999).”
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“Up to 15 % of patients suffering from treatment-resistant depression commit suicide (Wulsin et al. 1999; Isometsa et al. 1994).”
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Dallaspezia, S., & Benedetti, F. (2020) · Journal of Affective Disorders · doi:10.1016/j.jad.2020.05.104 · Cited by 20
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Recreational Physical Activity Ameliorates Some of the Negative Impact of Major Depression on Health-Related Quality of Life
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“These disorders affect mortality (Wulsin et al., 1999; Lawrence et al., 2010; Patten et al., 2011), but their main impact is through diminished functioning and lower health-related quality of life (HRQoL).”
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Depression with melancholic features is associated with higher long-term risk for dementia
do Couto, F. S., Lunet, N., Ginó, S., Chester, C., Freitas, V., Maruta, C., Figueira, M. L., & de Mendonça, A. (2016) · Journal of Affective Disorders · doi:10.1016/j.jad.2016.05.026 · Cited by 17
Anxiety and depression in inflammatory eye disease: exploring the potential impact of topical treatment frequency as a putative psychometric item
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Changes in severity of depressive symptoms and mortality: the Italian Longitudinal Study on Aging
Scafato, E., Galluzzo, L., Ghirini, S., Gandin, C., Rossi, A. L. D. D. O. C., Solfrizzi, V., Panza, F., Carlo, A. D., Maggi, S., & Farchi, G. (2012) · Psychological Medicine · doi:10.1017/s0033291712000645 · Cited by 17
“During the past decades the influence of depression on mortality has been investigated in numerous studies, the majority of which have demonstrated that depression may increase the risk of death, suggesting an overall stronger effect for men and a high correlation with cardiovascular disease (Wulsin et al. 1999).”
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Emotions and the Immune System
Kemeny, M. E. (2007) · Elsevier eBooks · doi:10.1016/b978-012088576-3/50035-6 · Cited by 17

Authors: Wulsin, L. R., Vaillant, G. E., & Wells, V. E.
Affiliations: University of Cincinnati (US)
Brigham and Women's Hospital (US)
ORCID: Wulsin, Lawson R.
Venue: Psychosomatic Medicine
Publisher: Ovid Technologies (Wolters Kluwer Health)
Published: 1999
Volume: 61
Issue: 1
Pages: 6-17
ISSN: 0033-3174 (ISSN-L)
DOI: 10.1097/00006842-199901000-00003
OpenAlex: W2057242026
Cited by: 703
References: 73
Citations by year: 2026: 3 · 2025: 9 · 2024: 10 · 2023: 10 · 2022: 17 · 2021: 18 · 2020: 24 · 2019: 19 · 2018: 29 · 2017: 17 · 2016: 30 · 2015: 29 · 2014: 32 · 2013: 46 · 2012: 31
FWCI: 5.14
Type: journal article
Language: en
Open access: closed
Locations: Psychosomatic Medicine (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Health and Mental Health
Social Sciences › Psychology › Clinical Psychology › Suicide and Self-Harm Studies
Health Sciences › Medicine › Psychiatry and Mental health › Mental Health Treatment and Access
Keywords: depression, mortality, suicide, cardiovascular disease, cancer mortality, mediators, psychiatric patients, community population, sex differences, risk factors
MeSH terms: Adult, Depressive Disorder, Female, Humans, Male, Middle Aged

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A Systematic Review of the Mortality of Depression

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