Background. Depressive disorders are associated with substantial risk of premature mortality. A number of factors may contribute to reported risk estimates, making it difficult to determine actual risk of excess mortality in community cases of depression. The aim of this study is to conduct a systematic review and meta-analysis of excess mortality in population-based studies of clinically defined depression. Methods. Population-based studies reporting all-cause mortality associated with a clinically defined depressive disorder were included in the systematic review. Estimates of relative risk for excess mortality in population-representative cases of clinical depressive disorders were extracted. A meta-analysis was conducted using Stata to pool estimates of excess mortality and identify sources of heterogeneity within the data. Results. Twenty-one studies reporting risk of excess mortality in clinical depression were identified. A significantly higher risk of mortality was found for major depression (RR 1.92 95% CI 1.65–2.23), but no significant difference was found for dysthymia (RR 1.37 95% CI 0.93–2.00). Relative risk of excess mortality was not significantly different following the adjustment of reported risk estimates. Conclusion. A mortality gradient was identified with increasing severity of clinical depression. Recognition of depressive symptoms in general practice and appropriate referral for evidence-based treatment may help improve outcomes, particularly in patients with comorbid physical disorders. 1. Introduction Depressive disorders make a substantial contribution to the global burden of disease [1–3]. Their contribution to disease burden is largely attributed to the high prevalence of, and disability caused by, depression [1]. Contribution to disease burden of premature mortality in individuals with depression is less well studied, with the exception of suicide and more recently coronary heart disease. Depressive disorders are a well-recognized risk factor for suicide [4], and increased treatment of depression has been associated with a decrease in suicide rates [5, 6]. Increased risk of excess all-cause mortality has previously been shown in psychiatric inpatients [7–9]. Excess mortality in psychiatric inpatients has been associated with conditions such as gastrointestinal infection and respiratory disease, and previously attributed to conditions within hospitals or asylums [10], although the introduction of modern psychiatric treatments and shorter duration of stay in hospitals has improved mortality outcomes for individuals
References
[1]
T. B. Ustun, J. L. Ayuso-Mateos, S. Chatterji, C. Mathers, and C. J. L. Murray, “Global burden of depressive disorders in the year 2000,” British Journal of Psychiatry, vol. 184, pp. 386–392, 2004.
[2]
C. J. L. Murray and A. D. Lopez, “Evidence-based health policy—lessons from the global burden of disease study,” Science, vol. 274, no. 5288, pp. 740–743, 1996.
[3]
C. D. Mathers, C. Stein, D. M. Fat, et al., “Global Burden of Disease 2000: version 2 methods and results,” Tech. Rep. 50, WHO, Geneva, Switzerland, 2002.
[4]
K. Hawton and K. van Heeringen, “Suicide,” The Lancet, vol. 373, no. 9672, pp. 1372–1381, 2009.
[5]
W. D. Hall, A. Mant, P. B. Mitchell, V. A. Rendle, I. B. Hickie, and P. McManus, “Association between antidepressant prescribing and suicide in Australia, 1991–2000: trend analysis,” British Medical Journal, vol. 326, no. 7397, pp. 1008–1011, 2003.
[6]
J. J. Mann, A. Apter, J. Bertolote et al., “Suicide prevention strategies: a systematic review,” Journal of the American Medical Association, vol. 294, no. 16, pp. 2064–2074, 2005.
[7]
D. W. Black, “Iowa record-linkage study: death rates in psychiatric patients,” Journal of Affective Disorders, vol. 50, no. 2-3, pp. 277–282, 1998.
[8]
P. Allebeck and B. Wistedt, “Mortality in schizophrenia. A ten-year follow-up based on the Stockholm county inpatient register,” Archives of General Psychiatry, vol. 43, no. 7, pp. 650–653, 1986.
[9]
M. Hamer, E. Stamatakis, and A. Steptoe, “Psychiatric hospital admissions, behavioral risk factors, and all-cause mortality: the Scottish Health Survey,” Archives of Internal Medicine, vol. 168, no. 22, pp. 2474–2479, 2008.
[10]
A. Sims, “Why the excess mortality from psychiatric illness?” British Medical Journal, vol. 294, no. 6578, pp. 986–987, 1987.
[11]
T. J. Craig and S. P. Lin, “Mortality among psychiatric inpatients. Age-adjusted comparison of populations before and after psychotropic drug era,” Archives of General Psychiatry, vol. 38, no. 8, pp. 935–938, 1981.
[12]
J. L. Geller, “The last half-century of psychiatric services as reflected in psychiatric services,” Psychiatric Services, vol. 51, no. 1, pp. 41–67, 2000.
[13]
W. Fakhoury and S. Priebe, “The process of deinstitutionalization: an international overview,” Current Opinion in Psychiatry, vol. 15, no. 2, pp. 187–192, 2002.
[14]
J. Ormel, M. Petukhova, S. Chatterji et al., “Disability and treatment of specific mental and physical disorders across the world,” British Journal of Psychiatry, vol. 192, no. 5, pp. 368–375, 2008.
[15]
J. C. Barefoot and M. Schroll, “Symptoms of depression, acute myocardial infarction, and total mortality in a community sample,” Circulation, vol. 93, no. 11, pp. 1976–1980, 1996.
[16]
N. Breslau, E. L. Peterson, L. R. Schultz, H. D. Chilcoat, and P. Andreski, “Major depression and stages of smoking: a longitudinal investigation,” Archives of General Psychiatry, vol. 55, no. 2, pp. 161–166, 1998.
[17]
L. C. Dierker, S. Avenevoli, M. Stolar, and K. R. Merikangas, “Smoking and depression: an examination of mechanisms of comorbidity,” American Journal of Psychiatry, vol. 159, no. 6, pp. 947–953, 2002.
[18]
K. M. Scott, M. A. McGee, M. A. Oakley Browne, and J. E. Wells, “Mental disorder comorbidity in Te Rau Hinengaro: the New Zealand Mental Health Survey,” Australian and New Zealand Journal of Psychiatry, vol. 40, no. 10, pp. 875–881, 2006.
[19]
L. Degenhardt, W. Hall, M. Lynskey, C. Coffey, and G. Patton, “The association between cannabis use and depression: a review of the evidence,” in Marijuana and Madness: Psychiatry and Neurobiology, D. J. Castle and R. Murray, Eds., Cambridge University Press, New York, NY, USA, 2004.
[20]
C. A. Roeloffs, A. Fink, J. Unützer, L. Tang, and K. B. Wells, “Problematic substance use, depressive symptoms, and gender in primary care,” Psychiatric Services, vol. 52, no. 9, pp. 1251–1253, 2001.
[21]
L. de Wit, A. van Straten, F. Lamers, P. Cuijpers, and B. Penninx, “Are sedentary television watching and computer use behaviors associated with anxiety and depressive disorders?” Psychiatry Research, vol. 186, no. 2-3, pp. 239–243, 2011.
[22]
M. H. L. van der Wal, T. Jaarsma, D. K. Moser, N. J. G. M. Veeger, W. H. Van Gilst, and D. J. Van Veldhuisen, “Compliance in heart failure patients: the importance of knowledge and beliefs,” European Heart Journal, vol. 27, no. 4, pp. 434–440, 2006.
[23]
E. H. B. Lin, W. Katon, M. Von Korff et al., “Relationship of depression and diabetes self-care, medication adherence, and preventive care,” Diabetes Care, vol. 27, no. 9, pp. 2154–2160, 2004.
[24]
J. H. Park, HA. K. Kim, J. H. Park, and J. H. Kim, “Differences in adherence to antihypertensive medication regimens according to psychiatric diagnosis: results of a Korean population-based study,” Psychosomatic Medicine, vol. 72, no. 1, pp. 80–87, 2010.
[25]
A. Sherwood, J. A. Blumenthal, R. Trivedi et al., “Relationship of depression to death or hospitalization in patients with heart failure,” Archives of Internal Medicine, vol. 167, no. 4, pp. 367–373, 2007.
[26]
S. Moussavi, S. Chatterji, E. Verdes, A. Tandon, V. Patel, and B. Ustun, “Depression, chronic diseases, and decrements in health: results from the World Health Surveys,” The Lancet, vol. 370, no. 9590, pp. 851–858, 2007.
[27]
A. L. Gross, J. J. Gallo, and W. W. Eaton, “Depression and cancer risk: 24 years of follow-up of the Baltimore epidemiologic catchment area sample,” Cancer Causes and Control, vol. 21, no. 2, pp. 191–199, 2010.
[28]
J. K. Kiecolt-Glaser and R. Glaser, “Depression and immune function central pathways to morbidity and mortality,” Journal of Psychosomatic Research, vol. 53, no. 4, pp. 873–876, 2002.
[29]
L. A. Pratt, R. M. BCrum, H. K. Aermenian, J. J. Gallo, and W. E. Eaton, “Coronary heart disease/myocardial infarction: depression, psychotropic medication, and risk of myocardial infarction. Prospective data from the Baltimore ECA follow-up,” Circulation, vol. 94, no. 12, pp. 3123–3129, 1996.
[30]
J. Licinio and M. L. Wong, “The role of inflammatory mediators in the biology of major depression: central nervous system cytokines modulate the biological substrate of depressive symptoms, regulate stress-responsive systems, and contribute to neurotoxicity and neuroprotection,” Molecular Psychiatry, vol. 4, no. 4, pp. 317–327, 1999.
[31]
S. Su, A. H. Miller, H. Snieder et al., “Common genetic contributions to depressive symptoms and inflammatory markers in middle-aged men: the twins heart study,” Psychosomatic Medicine, vol. 71, no. 2, pp. 152–158, 2009.
[32]
A. Steptoe, S. R. Kunz-Ebrecht, and N. Owen, “Lack of association between depressive symptoms and markers of immune and vascular inflammation in middle-aged men and women,” Psychological Medicine, vol. 33, no. 4, pp. 667–674, 2003.
[33]
R. B. Goldberg, “Cytokine and cytokine-like inflammation markers, endothelial dysfunction, and imbalanced coagulation in development of diabetes and its complications,” Journal of Clinical Endocrinology and Metabolism, vol. 94, no. 9, pp. 3171–3182, 2009.
[34]
G. K. Hansson, “Mechanisms of disease: inflammation, atherosclerosis, and coronary artery disease,” The New England Journal of Medicine, vol. 352, no. 16, pp. 1685–1626, 2005.
[35]
E. C. Harris and B. Barraclough, “Excess mortality of mental disorder,” British Journal of Psychiatry, vol. 173, pp. 11–53, 1998.
[36]
P. Cuijpers and F. Smit, “Excess mortality in depression: a meta-analysis of community studies,” Journal of Affective Disorders, vol. 72, no. 3, pp. 227–236, 2002.
[37]
L. R. Wulsin, G. E. Vaillant, and V. E. Wells, “A systematic review of the mortality of depression,” Psychosomatic Medicine, vol. 61, no. 1, pp. 6–17, 1999.
[38]
M. van den Akker, A. G. Schuurman, K. T. J. L. Ensinck, and F. Buntinx, “Depression as a risk factor for total mortality in the community: a meta-analysis,” Archives of Public Health, vol. 61, no. 6, pp. 313–332, 2003.
[39]
J. Seymour and T. B. Benning, “Depression, cardiac mortality and all-cause mortality,” Advances in Psychiatric Treatment, vol. 15, no. 2, pp. 107–113, 2009.
[40]
W. W. Eaton, S. S. Martins, G. Nestadt, O. J. Bienvenu, D. Clarke, and P. Alexandre, “The burden of mental disorders,” Epidemiologic Reviews, vol. 30, no. 1, pp. 1–14, 2008.
[41]
APA, Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR), Text Revision, American Psychiatric Association, Washington, DC, USA, 4th edition, 2000.
[42]
WHO, The ICD-10 Classification of Mental and Behavioural Disorders : Clinical Descriptions and Diagnostic Guidelines, World Health Organization, Geneva, Switzerland, 1992.
[43]
D. F. Stroup, J. A. Berlin, S. C. Morton et al., “Meta-analysis of observational studies in epidemiology: a proposal for reporting,” Journal of the American Medical Association, vol. 283, no. 15, pp. 2008–2012, 2000.
[44]
E. S. Paykel, G. L. Klerman, and B. A. Prusoff, “Treatment setting and clinical depression,” Archives of General Psychiatry, vol. 22, no. 1, pp. 11–21, 1970.
[45]
M. J. Bradburn, J. J. Deeks, and D. G. Altman, “Metan—a command for meta-analysis in Stata,” in Meta-Analysis in Stata: An Updated Collection from the Stata Journal, J. A. C. Sterne, Ed., StataCorp LP, College Station, Tex, USA, 2009.
[46]
R. J. Harris, M. J. Bradburn, J. J. Deeks, D. G. Altman, R. M. Harbord, and J. A. C. Sterne, “Metan: fixed- and random-effects meta-analysis,” Stata Journal, vol. 8, no. 1, pp. 3–28, 2008.
[47]
J. P. T. Higgins and S. G. Thompson, “Controlling the risk of spurious findings from meta-regression,” Statistics in Medicine, vol. 23, no. 11, pp. 1663–1682, 2004.
[48]
R. M. Harbord and J. P. T. Higgins, “Meta-regression in Stata,” Stata Journal, vol. 8, no. 4, pp. 493–519, 2008.
[49]
A. Mykletun, O. Bjerkeset, S. ？verland, M. Prince, M. Dewey, and R. Stewart, “Levels of anxiety and depression as predictors of mortality: the HUNT study,” British Journal of Psychiatry, vol. 195, no. 2, pp. 118–125, 2009.
[50]
J. A. Adamson, G. M. Price, E. Breeze, C. J. Bulpitt, and A. E. Fletcher, “Are older people dying of depression? Findings from the Medical Research Council Trial of the Assessment and Management of Older People in the Community,” Journal of the American Geriatrics Society, vol. 53, no. 7, pp. 1128–1132, 2005.
[51]
J. J. Gallo, H. R. Bogner, K. H. Morales, E. P. Post, T. T. Have, and M. L. Bruce, “Depression, cardiovascular disease, diabetes, and two-year mortality among older, primary-care patients,” American Journal of Geriatric Psychiatry, vol. 13, no. 9, pp. 748–755, 2005.
[52]
S. Mogga, M. Prince, A. Alem et al., “Outcome of major depression in Ethiopia: population-based study,” British Journal of Psychiatry, vol. 189, pp. 241–246, 2006.
[53]
J. Snowdon and F. Lane, “The botany survey: a longitudinal study of depression and cognitive impairment in an elderly population,” International Journal of Geriatric Psychiatry, vol. 10, no. 5, pp. 349–358, 1995.
[54]
A. F. Jorm, A. S. Henderson, D. W. K. Kay, and P. A. Jacomb, “Mortality in relation to dementia, depression and social integration in an elderly community sample,” International Journal of Geriatric Psychiatry, vol. 6, no. 1, pp. 5–11, 1991.
[55]
A. S. Henderson, A. E. Korten, P. A. Jacomb et al., “The course of depression in the elderly: a longitudinal community-based study in Australia,” Psychological Medicine, vol. 27, no. 1, pp. 119–129, 1997.
[56]
E. Bergdahl, J. M. C. Gustavsson, K. Kallin et al., “Depression among the oldest old: the Umea 85+ study,” International Psychogeriatrics, vol. 17, no. 4, pp. 557–575, 2005.
[57]
R. A. Schoevers, M. I. Geerlings, D. J. H. Deeg, T. J. Holwerda, C. Jonker, and A. T. F. Beekman, “Depression and excess mortality: evidence for a dose response relation in community living elderly,” International Journal of Geriatric Psychiatry, vol. 24, no. 2, pp. 169–176, 2009.
[58]
T. Pulska, K. Pahkala, P. Laippala, and S. L. Kivel？, “Six-year survival of depressed elderly Finns: a community study,” International Journal of Geriatric Psychiatry, vol. 12, no. 9, pp. 942–950, 1997.
[59]
I. A. Davidson, M. E. Dewey, and J. R. M. Copeland, “The relationship between mortality and mental disorder: evidence from the Liverpool longitudinal study,” International Journal of Geriatric Psychiatry, vol. 3, no. 2, pp. 95–98, 1988.
[60]
K. Engedal, “Mortality in the elderly—a 3-year follow-up of an elderly community sample,” International Journal of Geriatric Psychiatry, vol. 11, no. 5, pp. 467–471, 1996.
[61]
B. W. J. H. Penninx, S. W. Geerlings, D. J. H. Deeg, J. T. M. Van Eijk, W. Van Tilburg, and A. T. F. Beekman, “Minor and major depression and the risk of death in older persons,” Archives of General Psychiatry, vol. 56, no. 10, pp. 889–895, 1999.
[62]
A. Kouzis, W. W. Eaton, and P. J. Leaf, “Psychopathology and mortality in the general population,” Social Psychiatry and Psychiatric Epidemiology, vol. 30, no. 4, pp. 165–170, 1995.
[63]
D. Zheng, C. A. Macera, J. B. Croft, W. H. Giles, D. Davis, and W. K. Scott, “Major depression and all-cause mortality among white adults in the United States,” Annals of Epidemiology, vol. 7, no. 3, pp. 213–218, 1997.
[64]
J. M. Murphy, R. R. Monson, and D. C. Olivier, “Affective disorders and mortality. A general population study,” Archives of General Psychiatry, vol. 44, no. 5, pp. 473–480, 1987.
[65]
M. L. Bruce, P. J. Leaf, G. P. M. Rozal, L. Florio, and R. A. Hoff, “Psychiatric status and 9-year mortality data in the New Haven Epidemiologic Catchment Area study,” American Journal of Psychiatry, vol. 151, no. 5, pp. 716–721, 1994.
[66]
T. Pulska, K. Pahkala, P. Laippalla, and S. L. Kivel？, “Major depression as a predictor of premature deaths in elderly people in Finland: a community study,” Acta Psychiatrica Scandinavica, vol. 97, no. 6, pp. 408–411, 1998.
[67]
T. Pulska, K. Pahkala, P. Laippala, and S. L. Kivel？, “Survival of elderly Finns suffering from dysthymic disorder: a community study,” Social Psychiatry and Psychiatric Epidemiology, vol. 33, no. 7, pp. 319–325, 1998.
[68]
A. Aromaa, R. Raitasalo, A. Reunanen et al., “Depression and cardiovascular diseases,” Acta Psychiatrica Scandinavica, Supplement, vol. 89, supplement 377, pp. 77–82, 1994.
[69]
D. J. Vinkers, M. L. Stek, J. Gussekloo, R. C. van der Mast, and R. G. J. Westendorp, “Does depression in old age increase only cardiovascular mortality? The Leiden 85-plus study,” International Journal of Geriatric Psychiatry, vol. 19, no. 9, pp. 852–857, 2004.
[70]
M. Jokela, J. Ferrie, and M. Kivim？ki, “Childhood problem behaviors and death by midlife: the British national child development study,” Journal of the American Academy of Child and Adolescent Psychiatry, vol. 48, no. 1, pp. 19–24, 2009.
[71]
L. S. Williams, S. S. Ghose, and R. W. Swindle, “Depression and other mental health diagnoses increase mortality risk after ischemic stroke,” American Journal of Psychiatry, vol. 161, no. 6, pp. 1090–1095, 2004.
[72]
M. Ansseau, M. Dierick, F. Buntinkx et al., “High prevalence of mental disorders in primary care,” Journal of Affective Disorders, vol. 78, no. 1, pp. 49–55, 2004.
[73]
J. Barth, M. Schumacher, and C. Herrmann-Lingen, “Depression as a risk factor for mortality in patients with coronary heart disease: a meta-analysis,” Psychosomatic Medicine, vol. 66, no. 6, pp. 802–813, 2004.
[74]
P. G. Surtees, N. W. J. Wainwright, R. N. Luben, N. J. Wareham, S. A. Bingham, and K. T. Khaw, “Depression and ischemic heart disease mortality: evidence from the EPIC-Norfolk United Kingdom prospective cohort study,” American Journal of Psychiatry, vol. 165, no. 4, pp. 515–523, 2008.
[75]
M. M. Desai, “The effects of psychiatric history on cancer outcomes: longitudinal evidence from a community sample of women,” Dissertation Abstracts International: Section B: The Sciences and Engineering, vol. 58, no. 4B, p. 1828, 1997.
[76]
P. Cuijpers and R. A. Schoevers, “Increased mortality in depressive disorders: a review,” Current Psychiatry Reports, vol. 6, no. 6, pp. 430–437, 2004.
[77]
J. Angst and M. Preisig, “Outcome of a clinical cohort of unipolar, bipolar and schizoaffective patients. Results of a prospective study from 1959 to 1985,” Schweizer Archiv fur Neurologie und Psychiatrie, vol. 146, no. 1, pp. 17–23, 1995.
[78]
E. Kjelsberg, “Adolescent psychiatric in-patients. A high-risk group for premature death,” British Journal of Psychiatry, vol. 176, pp. 121–125, 2000.
[79]
O. Ostman, “Child and adolescent psychiatric patients in adulthood,” Acta Psychiatrica Scandinavica, vol. 84, no. 1, pp. 40–45, 1991.
[80]
M. Pelkonen, M. Marttunen, E. Pulkkinen, A. M. Koivisto, P. Laippala, and H. Aro, “Excess mortality among former adolescent male out-patients,” Acta Psychiatrica Scandinavica, vol. 94, no. 1, pp. 60–66, 1996.
[81]
M. M. Weissman, S. Wolk, R. B. Goldstein et al., “Depressed adolescents grown up,” Journal of the American Medical Association, vol. 281, no. 18, pp. 1707–1713, 1999.
[82]
E. Fombonne, G. Wostear, V. Cooper, R. Harrington, and M. Rutter, “The Maudsley long-term follow-up of child and adolescent depression: 2. Suicidality, criminality and social dysfunction in adulthood,” British Journal of Psychiatry, vol. 179, pp. 218–223, 2001.
[83]
H. C. Steinhausen, M. Meier, and J. Angst, “The Zurich long-term outcome study of child and adolescent psychiatric disorders in males,” Psychological Medicine, vol. 28, no. 2, pp. 375–383, 1998.
[84]
J. Neeleman, S. Wessely, and M. Wadsworth, “Predictors of suicide, accidental death, and premature natural death in a general-population birth cohort,” The Lancet, vol. 351, no. 9096, pp. 93–97, 1998.
[85]
M. G. Sawyer, F. M. Arney, P. A. Baghurst, et al., The Mental Health of Young People in Australia: Child and Adolescent Component of the National Survey of Mental Health and Well-Being, Mental Health and Special Programs Branch CDoHaAC, Canberra, Australia, 2000.
[86]
H. Green, A. McGinnity, H. Meltzer, T. Ford, and R. Goodman, Mental Health of CHildren and Young People in Great Britain, Executive tOfNSobotDoHatS, 2005.
