{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T17:25:31Z","timestamp":1790270731246,"version":"4.1.0"},"reference-count":158,"publisher":"Royal College of Psychiatrists","issue":"2","license":[{"start":{"date-parts":[[2025,4,4]],"date-time":"2025-04-04T00:00:00Z","timestamp":1743724800000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["cambridge.org"],"crossmark-restriction":true},"short-container-title":["Br J Psychiatry"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:sec id=\"S0007125025000182_as1\"><jats:title>Background<\/jats:title><jats:p>Antidepressants are effective for depression, but most evidence excludes individuals with comorbid physical conditions.<\/jats:p><\/jats:sec><jats:sec id=\"S0007125025000182_as5\"><jats:title>Aims<\/jats:title><jats:p>To assess antidepressants\u2019 efficacy and tolerability in individuals with depression and comorbid physical conditions.<\/jats:p><\/jats:sec><jats:sec id=\"S0007125025000182_as2\"><jats:title>Methods<\/jats:title><jats:p>Systematic review and network meta-analysis of randomised controlled trials (RCTs). Co-primary outcomes were efficacy on depressive symptoms and tolerability (participants dropping out because of adverse events). Bias was assessed with the Cochrane Risk-of-Bias 2 tool and certainty of estimates with the Confidence in Network Meta-Analysis approach. A study protocol was registered in advance (<jats:uri xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"https:\/\/osf.io\/9cjhe\/\">https:\/\/osf.io\/9cjhe\/<\/jats:uri>).<\/jats:p><\/jats:sec><jats:sec id=\"S0007125025000182_as3\"><jats:title>Results<\/jats:title><jats:p>Of the 115 included RCTs, 104 contributed to efficacy (7714 participants) and 82 to tolerability (6083 participants). The mean age was 55.7 years and 51.9% of participants were female. Neurological and cardiocirculatory conditions were the most represented (26.1% and 18.3% of RCTs, respectively). The following antidepressants were more effective than placebo: imipramine, nortriptyline, amitriptyline, desipramine, sertraline, paroxetine, citalopram, fluoxetine, escitalopram, mianserin, mirtazapine and agomelatine, with standardised mean differences ranging from \u22121.01 (imipramine) to \u22120.34 (escitalopram). Sertraline and paroxetine were effective for the largest number of ICD-11 disease subgroups (four out of seven). In terms of tolerability, sertraline, imipramine and nortriptyline were less tolerated than placebo, with relative risks ranging from 1.47 (sertraline) to 3.41 (nortriptyline). For both outcomes, certainty of evidence was \u2018low\u2019 or \u2018very low\u2019 for most comparisons.<\/jats:p><\/jats:sec><jats:sec id=\"S0007125025000182_as4\"><jats:title>Conclusion<\/jats:title><jats:p>Antidepressants are effective in individuals with comorbid physical conditions, although tolerability is a relevant concern. Selective serotonin reuptake inhibitors (SSRIs) have the best benefit\u2013risk profile, making them suitable as first-line treatments, while tricyclics are highly effective but less tolerated than SSRIs and placebo.<\/jats:p><\/jats:sec>","DOI":"10.1192\/bjp.2025.18","type":"journal-article","created":{"date-parts":[[2025,4,4]],"date-time":"2025-04-04T05:04:23Z","timestamp":1743743063000},"page":"553-566","update-policy":"https:\/\/doi.org\/10.1017\/policypage","source":"Crossref","is-referenced-by-count":10,"title":["Efficacy and tolerability of antidepressants in individuals suffering from physical conditions and depressive disorders: network meta-analysis"],"prefix":"10.1192","volume":"227","author":[{"given":"Beatrice","family":"De Luca","sequence":"first","affiliation":[{"name":"University of 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