{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T03:22:53Z","timestamp":1793848973756,"version":"4.6.1"},"reference-count":242,"publisher":"BMJ","issue":"1","license":[{"start":{"date-parts":[[2024,1,18]],"date-time":"2024-01-18T00:00:00Z","timestamp":1705536000000},"content-version":"unspecified","delay-in-days":17,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Ment Health"],"accepted":{"date-parts":[[2023,12,11]]},"published-print":{"date-parts":[[2024,1]]},"abstract":"<jats:sec>\n                  <jats:title>Question<\/jats:title>\n                  <jats:p>Tricyclic antidepressants are used to treat depression worldwide, but the adverse effects have not been systematically assessed. Our objective was to assess the beneficial and harmful effects of all tricyclic antidepressants for adults with major depressive disorder.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Study selection and analysis<\/jats:title>\n                  <jats:p>We conducted a systematic review with meta-analysis and trial sequential analysis. We searched CENTRAL, MEDLINE, Embase, LILACS and other sources from inception to January 2023 for randomised clinical trials comparing tricyclic antidepressants versus placebo or \u2018active placebo\u2019 for adults with major depressive disorder. The primary outcomes were depressive symptoms measured on the 17-item Hamilton Depression Rating Scale (HDRS-17), serious adverse events and quality of life. The minimal important difference was defined as three points on the HDRS-17.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Findings<\/jats:title>\n                  <jats:p>We included 103 trials randomising 10\u2009590 participants. All results were at high risk of bias, and the certainty of the evidence was very low or low. All trials only assessed outcomes at the end of the treatment period at a maximum of 12 weeks after randomisation. Meta-analysis and trial sequential analysis showed evidence of a beneficial effect of tricyclic antidepressants compared with placebo (mean difference \u22123.77 HDRS-17 points; 95% CI \u22125.91 to \u22121.63; 17 trials). Meta-analysis showed evidence of a harmful effect of tricyclic antidepressants compared with placebo on serious adverse events (OR 2.78; 95%\u2009CI 2.18 to 3.55; 35 trials), but the required information size was not reached. Only 2 out of 103 trials reported on quality of life and t-tests showed no evidence of a difference.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>The long-term effects of tricyclic antidepressants and the effects on quality of life are unknown. Short-term results suggest that tricyclic antidepressants may reduce depressive symptoms while also increasing the risks of serious adverse events, but these results were based on low and very low certainty evidence.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>PROSPERO registration number<\/jats:title>\n                  <jats:p>CRD42021226161.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/bmjment-2023-300730","type":"journal-article","created":{"date-parts":[[2024,1,22]],"date-time":"2024-01-22T06:35:31Z","timestamp":1705905331000},"page":"e300730","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":23,"title":["Beneficial and harmful effects of tricyclic antidepressants for adults with major depressive disorder: a systematic review with meta-analysis and trial sequential analysis"],"prefix":"10.1136","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7756-4694","authenticated-orcid":false,"given":"Caroline Barkholt","family":"Kamp","sequence":"first","affiliation":[{"name":"Copenhagen Trial Unit, Centre for Clinical Intervention Research, Copenhagen University Hospital \u2013 Rigshospitalet, Copenhagen, Denmark"},{"name":"Department of Regional Health Research, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9837-1958","authenticated-orcid":false,"given":"Johanne Juul","family":"Petersen","sequence":"additional","affiliation":[{"name":"Copenhagen Trial Unit, Centre for Clinical Intervention Research, Copenhagen University Hospital \u2013 Rigshospitalet, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pascal","family":"Faltermeier","sequence":"additional","affiliation":[{"name":"Copenhagen Trial Unit, Centre for Clinical Intervention Research, Copenhagen University Hospital \u2013 Rigshospitalet, Copenhagen, Denmark"},{"name":"MSH Medical School Hamburg, University of Applied Sciences and Medical University, Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"Juul","sequence":"additional","affiliation":[{"name":"Copenhagen Trial Unit, Centre for Clinical Intervention Research, Copenhagen University Hospital \u2013 Rigshospitalet, Copenhagen, Denmark"},{"name":"Psychotherapeutic Center Stolpeg\u00e5rd, Gentofte, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8358-6259","authenticated-orcid":false,"given":"Faiza","family":"Siddiqui","sequence":"additional","affiliation":[{"name":"Copenhagen Trial Unit, Centre for Clinical Intervention Research, Copenhagen University Hospital \u2013 Rigshospitalet, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8566-3660","authenticated-orcid":false,"given":"Marija","family":"Barbateskovic","sequence":"additional","affiliation":[{"name":"Copenhagen Trial Unit, Centre for Clinical Intervention Research, Copenhagen University Hospital \u2013 Rigshospitalet, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas Torp","family":"Kristensen","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Gentofte Hospital, Hellerup, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanna","family":"Moncrieff","sequence":"additional","affiliation":[{"name":"Division of Psychiatry, University College London (honorary for MAH), London, UK"},{"name":"Department of Research and Development, North East London NHS Foundation Trust, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1318-2029","authenticated-orcid":false,"given":"Mark Abie","family":"Horowitz","sequence":"additional","affiliation":[{"name":"Division of Psychiatry, University College London (honorary for MAH), London, UK"},{"name":"Department of Research and Development, North East London NHS Foundation Trust, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2956-2969","authenticated-orcid":false,"given":"Michael Pascal","family":"Hengartner","sequence":"additional","affiliation":[{"name":"Department of Applied Psychology, Zurich Universities of Applied Sciences, Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irving","family":"Kirsch","sequence":"additional","affiliation":[{"name":"Program in Placebo Studies, Harvard Medical School, Boston, Massachusetts, 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