{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T20:12:17Z","timestamp":1792613537199,"version":"4.5.0"},"reference-count":328,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,9,15]],"date-time":"2025-09-15T00:00:00Z","timestamp":1757894400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["World Psychiatry"],"published-print":{"date-parts":[[2025,10]]},"abstract":"\n Depression has been reported to be associated with premature mortality. However, no meta\u2010analysis has comprehensively examined all\u2010cause and cause\u2010specific mortality risk in people with this condition, focusing also on possible aggravating and attenuating factors, including antidepressant treatment. We conducted a systematic review and meta\u2010analysis of cohort studies to synthesize mortality risk estimates associated with depression (major depressive disorder and dysthymia) due to any and specific causes, and when depression is accompanied by comorbid conditions. Effects of antidepressant medication and electroconvulsive therapy (ECT), and other potential moderators of mortality risk, were evaluated. We searched EMBASE, Medline and PsycINFO databases up to January 26, 2025, pooling mortality estimates using random\u2010effect models. Publication bias, subgroup and meta\u2010regression analyses, and quality assessment (Newcastle\u2010Ottawa Scale) were performed. Across 268 studies, 10,842,094 individuals with depression and 2,837,933,536 control subjects were included. All\u2010cause mortality was doubled in people with depression versus no depression\/general population controls (relative risk, RR=2.10, 95% CI: 1.87\u20102.35, I\n 2<\/jats:sup>\n =99.9%), being especially high for suicide (RR=9.89, 95% CI: 7.59\u201012.88, I\n 2<\/jats:sup>\n =99.6%), but also elevated for natural causes (RR=1.63, 95% CI: 1.51\u20101.75, I\n 2<\/jats:sup>\n =99.6%). Among individuals with versus without depression matched for comorbid conditions, the depression\u2010associated mortality risk was also significantly elevated (RR=1.29, 95% CI: 1.21\u20101.37, I\n 2<\/jats:sup>\n =99.9%). Depression with versus without psychotic symptoms (RR=1.61, 95% CI: 1.45\u20101.78, I\n 2<\/jats:sup>\n =6.3%), and treatment\u2010resistant versus non\u2010treatment\u2010resistant depression (RR=1.27, 95% CI: 1.16\u20101.39, I\n 2<\/jats:sup>\n =85.3%), conferred an incremental mortality risk. Antidepressant use (versus no antidepressant use) was associated with significantly lower all\u2010cause mortality in people with depression (RR=0.79, 95% CI: 0.68\u20100.93, I\n 2<\/jats:sup>\n =99.2%). ECT use (versus no ECT use) was associated with reduced all\u2010cause mortality (RR=0.73, 95% CI: 0.66\u20100.82, I\n 2<\/jats:sup>\n =0%), natural\u2010cause mortality (RR=0.76, 95% CI: 0.59\u20100.97, I\n 2<\/jats:sup>\n =12.0%), and suicide (RR=0.67, 95% CI: 0.53\u20100.85, I\n 2<\/jats:sup>\n =32.3%). Our results affirm heightened mortality risk in depression, identify clinically relevant patient subgroups with increased mortality risk, and highlight mortality\u2010reducing effects of antidepressant treatment and ECT. Multipronged intervention approaches targeting physical health improvement and suicide risk alleviation, optimizing antidepressant treatment, and pursuing early identification and effective interventions for psychotic and treatment\u2010resistant depression, could help reduce this mortality gap, which is still growing.\n <\/jats:p>","DOI":"10.1002\/wps.21354","type":"journal-article","created":{"date-parts":[[2025,9,15]],"date-time":"2025-09-15T08:23:34Z","timestamp":1757924614000},"page":"404-421","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":56,"title":["All\u2010cause and cause\u2010specific mortality in people with depression: a large\u2010scale systematic review and meta\u2010analysis of relative risk and aggravating or attenuating factors, including antidepressant treatment"],"prefix":"10.1002","volume":"24","author":[{"given":"Joe Kwun Nam","family":"Chan","sequence":"first","affiliation":[{"name":"Department of Psychiatry, Li Ka Shing Faculty of Medicine University of Hong Kong Hong Kong SAR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Solmi","sequence":"additional","affiliation":[{"name":"SCIENCES lab, Department of Psychiatry University of Ottawa Ottawa ON Canada"},{"name":"Regional Centre for the Treatment of Eating Disorders and On Track: Champlain First Episode Psychosis Program, Department of Mental Health Ottawa Hospital Ottawa ON Canada"},{"name":"Clinical Epidemiology Program Ottawa Hospital Research Institute, University of Ottawa Ottawa ON Canada"},{"name":"Department of Child and Adolescent Psychiatry Charit\u00e9 Universit\u00e4tsmedizin Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heidi Ka Ying","family":"Lo","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Li Ka Shing Faculty of Medicine University of Hong Kong Hong Kong SAR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle Wai Yan","family":"Chan","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Li Ka Shing Faculty of Medicine University of Hong Kong Hong Kong SAR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leo Long Tin","family":"Choo","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Li Ka Shing Faculty of Medicine University of Hong Kong Hong Kong SAR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric Tsz Him","family":"Lai","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Kwai Chung Hospital Hong Kong Hong Kong SAR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Corine Sau Man","family":"Wong","sequence":"additional","affiliation":[{"name":"School of Public Health, Li Ka Shing Faculty of Medicine University of Hong Kong Hong Kong SAR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph U.","family":"Correll","sequence":"additional","affiliation":[{"name":"Department of Child and Adolescent Psychiatry Charit\u00e9 Universit\u00e4tsmedizin Berlin Germany"},{"name":"Department of Psychiatry Zucker Hillside Hospital, Northwell Health Glen Oaks NY USA"},{"name":"Department of Psychiatry and Molecular Medicine Zucker School of Medicine at Hofstra\/Northwell Hempstead NY USA"},{"name":"German Center for Mental Health (DZPG) partner site Berlin Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wing Chung","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Li Ka Shing Faculty of Medicine University of Hong Kong Hong Kong SAR China"},{"name":"State Key Laboratory of Brain and Cognitive Sciences University of Hong Kong Hong Kong SAR China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,9,15]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"crossref","first-page":"957","DOI":"10.1016\/S0140-6736(21)02141-3","article-title":"Time for united action on depression: a Lancet\u2010World Psychiatric Association Commission","volume":"399","author":"Herrman H","year":"2022","journal-title":"Lancet"},{"key":"e_1_2_6_3_1","doi-asserted-by":"crossref","first-page":"2299","DOI":"10.1016\/S0140-6736(18)31948-2","article-title":"Depression","volume":"392","author":"Malhi GS","year":"2018","journal-title":"Lancet"},{"key":"e_1_2_6_4_1","doi-asserted-by":"crossref","first-page":"1357","DOI":"10.1016\/S0140-6736(17)32802-7","article-title":"Comparative efficacy and acceptability of 21 antidepressant drugs for the acute treatment of adults with major depressive disorder: a systematic review and network meta\u2010analysis","volume":"391","author":"Cipriani 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