{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T22:30:29Z","timestamp":1788820229439,"version":"build-2803163510"},"reference-count":46,"publisher":"Royal College of Psychiatrists","issue":"5","license":[{"start":{"date-parts":[[2024,12,5]],"date-time":"2024-12-05T00:00:00Z","timestamp":1733356800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100013373","name":"NIHR Oxford Biomedical Research Centre","doi-asserted-by":"publisher","award":["NIHR203316"],"award-info":[{"award-number":["NIHR203316"]}],"id":[{"id":"10.13039\/501100013373","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100013373","name":"NIHR Oxford Biomedical Research Centre","doi-asserted-by":"publisher","award":["RP-2017-08-ST2-006"],"award-info":[{"award-number":["RP-2017-08-ST2-006"]}],"id":[{"id":"10.13039\/501100013373","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["cambridge.org"],"crossmark-restriction":true},"short-container-title":["Br J Psychiatry"],"published-print":{"date-parts":[[2025,5]]},"abstract":"<jats:sec id=\"S0007125024001946_sec_a1\"><jats:title>Background<\/jats:title><jats:p>Antidepressants\u2019 effects are established in randomised controlled trials (RCTs), but not in the real world.<\/jats:p><\/jats:sec><jats:sec id=\"S0007125024001946_sec_a2\"><jats:title>Aims<\/jats:title><jats:p>To investigate real-world comparative effects of antidepressants for depression and compare them with RCTs.<\/jats:p><\/jats:sec><jats:sec id=\"S0007125024001946_sec_a3\" sec-type=\"methods\"><jats:title>Method<\/jats:title><jats:p>We performed a cohort study based on the QResearch database. We included people with a newly recorded diagnosis of depression, exposed to licensed antidepressants in the UK. We assessed all-cause dropouts (acceptability), dropouts for adverse events (tolerability), occurrence of at least one adverse event (safety), and response and remission on the Patient Health Questionnaire (PHQ)-9 (effectiveness) at 2 and 12 months. Logistic regressions were used to compute adjusted-odds ratio (aOR) with 99% CIs, assessing the associations between exposure to each antidepressant against fluoxetine (comparator) and outcomes of interest. We compared estimates from the real world with RCTs using ratio-of-odds ratio (ROR) with 95% CI.<\/jats:p><\/jats:sec><jats:sec id=\"S0007125024001946_sec_a4\" sec-type=\"results\"><jats:title>Results<\/jats:title><jats:p>A total of 673 177 depressed people were studied: females 57.1%, mean age 42.8 (s.d. 17.7) years, mean baseline PHQ-9 17.1 (s.d. 5.0) (moderately severe depression). At 2 months, antidepressant acceptability was 61.4%, tolerability 94.4%, safety 54.5%, PHQ-9 decreased to 12.3 (s.d. 6.5). At 12 months, acceptability was 12.3%, tolerability 87.5%, safety 28.8%, PHQ-9 12.9 (s.d. 6.8). In the short and long term, tricyclics, mirtazapine and trazodone were worse than fluoxetine for most outcomes; citalopram had better acceptability than fluoxetine (aOR 0.95; 99% CI 0.92, 0.97), sertraline had lower tolerability (aOR 1.12; 99% CI 1.06, 1.18), and both citalopram and sertraline had lower safety (aOR 1.17 and 1.25, respectively). In the long term, citalopram had better acceptability (aOR 0.78; 99% CI 0.76, 0.81) and effectiveness (aOR 1.12 for both response and remission), but worse tolerability (aOR 1.09; 99% CI 1.06, 1.13) and safety (aOR 1.12; 99% CI 1.08, 1.16). Observational and randomised data were similar for citalopram and sertraline, while there was some difference for drugs less prescribed in the real world.<\/jats:p><\/jats:sec><jats:sec id=\"S0007125024001946_sec_a5\" sec-type=\"conclusions\"><jats:title>Conclusions<\/jats:title><jats:p>Antidepressants showed low acceptability, moderate-to-high tolerability and safety, and small-to-moderate effectiveness in the real world. Real-world and RCT estimates showed similar findings only when the analyses were carried out using large datasets; otherwise, the results diverged.<\/jats:p><\/jats:sec>","DOI":"10.1192\/bjp.2024.194","type":"journal-article","created":{"date-parts":[[2024,12,5]],"date-time":"2024-12-05T07:34:29Z","timestamp":1733384069000},"page":"278-287","update-policy":"https:\/\/doi.org\/10.1017\/policypage","source":"Crossref","is-referenced-by-count":16,"title":["Real-world effects of antidepressants for depressive disorder in primary care: population-based cohort study"],"prefix":"10.1192","volume":"226","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2478-7763","authenticated-orcid":false,"given":"Franco","family":"De Crescenzo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5984-8696","authenticated-orcid":false,"given":"Riccardo","family":"De Giorgi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cesar","family":"Garriga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiang","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5383-5365","authenticated-orcid":false,"given":"Seena","family":"Fazel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Orestis","family":"Efthimiou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Hippisley-Cox","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5179-8321","authenticated-orcid":false,"given":"Andrea","family":"Cipriani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"170","published-online":{"date-parts":[[2024,12,5]]},"reference":[{"key":"S0007125024001946_ref11","doi-asserted-by":"publisher","DOI":"10.1016\/S2666-7568(22)00186-6"},{"key":"S0007125024001946_ref7","volume-title":"Depression \u2013 The NICE Guideline to the Treatment and Management of Depression in Adults (updated edition)","year":"2022"},{"key":"S0007125024001946_ref27","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1819.2011.02275.x"},{"key":"S0007125024001946_ref8","unstructured":"8 NHS Business Services Authority Statistics and Data Science. 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