{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T15:01:27Z","timestamp":1791385287951,"version":"4.3.3"},"reference-count":86,"publisher":"American Medical Association (AMA)","issue":"12","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Psychiatry"],"published-print":{"date-parts":[[2023,12,1]]},"abstract":"Importance<\/jats:title>Every third to sixth patient with medical diseases receives antidepressants, but regulatory trials typically exclude comorbid medical diseases. Meta-analyses of antidepressants have shown small to medium effect sizes, but generalizability to clinical settings is unclear, where medical comorbidity is highly prevalent.<\/jats:p><\/jats:sec>Objective<\/jats:title>To perform an umbrella systematic review of the meta-analytic evidence and meta-analysis of the efficacy and safety of antidepressant use in populations with medical diseases and comorbid depression.<\/jats:p><\/jats:sec>Data Sources<\/jats:title>PubMed and EMBASE were searched from inception until March 31, 2023, for systematic reviews with or without meta-analyses of randomized clinical trials (RCTs) examining the efficacy and safety of antidepressants for treatment or prevention of comorbid depression in any medical disease.<\/jats:p><\/jats:sec>Study Selection<\/jats:title>Meta-analyses of placebo- or active-controlled RCTs studying antidepressants for depression in individuals with medical diseases.<\/jats:p><\/jats:sec>Data Extraction and Synthesis<\/jats:title>Data extraction and quality assessment using A Measurement Tool for the Assessment of Multiple Systematic Reviews (AMSTAR-2 and AMSTAR-Content) were performed by pairs of independent reviewers following PRISMA guidelines. When several meta-analyses studied the same medical disease, the largest meta-analysis was included. Random-effects meta-analyses pooled data on the primary outcome (efficacy), key secondary outcomes (acceptability and tolerability), and additional secondary outcomes (response and remission).<\/jats:p><\/jats:sec>Main Outcomes and Measures<\/jats:title>Antidepressant efficacy presented as standardized mean differences (SMDs) and tolerability (discontinuation for adverse effects) and acceptability (all-cause discontinuation) presented as risk ratios (RRs).<\/jats:p><\/jats:sec>Results<\/jats:title>Of 6587 references, 176 systematic reviews were identified in 43 medical diseases. Altogether, 52 meta-analyses in 27 medical diseases were included in the evidence synthesis (mean [SD] AMSTAR-2 quality score,\u20099.3\u2009[3.1], with a maximum possible of\u200916; mean [SD] AMSTAR-Content score,\u20092.4\u2009[1.9], with a maximum possible of\u20099). Across medical diseases (23 meta-analyses), antidepressants improved depression vs placebo (SMD,\u20090.42 [95% CI,\u20090.30-0.54]; I<\/jats:italic>2<\/jats:sup>\u2009=\u200976.5%), with the largest SMDs for myocardial infarction (SMD,\u20091.38 [95% CI, 0.82-1.93]), functional chest pain (SMD,\u20090.87 [95% CI, 0.08-1.67]), and coronary artery disease (SMD,\u20090.83 [95% CI, 0.32-1.33]) and the smallest for low back pain (SMD,\u20090.06 [95% CI, 0.17-0.39]) and traumatic brain injury (SMD,\u20090.08 [95% CI, \u22120.28 to 0.45]). Antidepressants showed worse acceptability (24 meta-analyses; RR,\u20091.17 [95% CI,\u20091.02-1.32]) and tolerability (18 meta-analyses; RR,\u20091.39 [95% CI,\u20091.13-1.64]) compared with placebo. Antidepressants led to higher rates of response (8 meta-analyses; RR,\u20091.54 [95% CI,\u20091.14-1.94]) and remission (6 meta-analyses; RR,\u20091.43 [95% CI,\u20091.25-1.61]) than placebo. Antidepressants more likely prevented depression than placebo (7 meta-analyses; RR,\u20090.43 [95% CI,\u20090.33-0.53]).<\/jats:p><\/jats:sec>Conclusions and Relevance<\/jats:title>The results of this umbrella systematic review of meta-analyses found that antidepressants are effective and safe in treating and preventing depression in patients with comorbid medical disease. However, few large, high-quality RCTs exist in most medical diseases.<\/jats:p><\/jats:sec>","DOI":"10.1001\/jamapsychiatry.2023.2983","type":"journal-article","created":{"date-parts":[[2023,9,6]],"date-time":"2023-09-06T15:03:26Z","timestamp":1694012606000},"page":"1196","source":"Crossref","is-referenced-by-count":47,"title":["Efficacy and Safety of Antidepressants in Patients With Comorbid Depression and Medical Diseases"],"prefix":"10.1001","volume":"80","author":[{"given":"Ole","family":"K\u00f6hler-Forsberg","sequence":"first","affiliation":[{"name":"Psychosis Research Unit, Aarhus University Hospital\u2013Psychiatry, Aarhus, Denmark"},{"name":"Department of Clinical Medicine, Aarhus University, Aarhus, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria","family":"Stiglbauer","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Neuroscience, Campus Benjamin Franklin, Charit\u00e9\u2013Universit\u00e4tsmedizin Berlin, Berlin, 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