{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T13:58:27Z","timestamp":1780063107539,"version":"3.54.0"},"reference-count":30,"publisher":"SAGE Publications","issue":"10","license":[{"start":{"date-parts":[[2016,10,1]],"date-time":"2016-10-01T00:00:00Z","timestamp":1475280000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["J R Soc Med"],"published-print":{"date-parts":[[2016,10]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To quantify the risk of suicidality and violence when selective serotonin and serotonin-norepinephrine reuptake inhibitors are given to adult healthy volunteers with no signs of a mental disorder.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design<\/jats:title>\n                    <jats:p>Systematic review and meta-analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Main outcome measure<\/jats:title>\n                    <jats:p>Harms related to suicidality, hostility, activation events, psychotic events and mood disturbances.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Setting<\/jats:title>\n                    <jats:p>Published trials identified by searching PubMed and Embase and clinical study reports obtained from the European and UK drug regulators.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Participants<\/jats:title>\n                    <jats:p>Double-blind, placebo-controlled trials in adult healthy volunteers that reported on suicidality or violence or precursor events to suicidality or violence.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A total of 5787 publications were screened and 130 trials fulfilled our inclusion criteria. The trials were generally uninformative; 97 trials did not report the randomisation method, 75 trials did not report any discontinuations and 63 trials did not report any adverse events or lack thereof. Eleven of the 130 published trials and two of 29 clinical study reports we received from the regulatory agencies presented data for our meta-analysis. Treatment of adult healthy volunteers with antidepressants doubled their risk of harms related to suicidality and violence, odds ratio 1.85 (95% confidence interval 1.11 to 3.08, p\u2009=\u20090.02, I\n                      <jats:sup>2\u2009<\/jats:sup>\n                      =\u200918%). The number needed to treat to harm one healthy person was 16 (95% confidence interval 8 to 100; Mantel-Haenszel risk difference 0.06). There can be little doubt that we underestimated the harms of antidepressants, as we only had access to the published articles for 11 of our 13 trials.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Antidepressants double the occurrence of events in adult healthy volunteers that can lead to suicide and violence.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/0141076816666805","type":"journal-article","created":{"date-parts":[[2016,10,11]],"date-time":"2016-10-11T19:13:32Z","timestamp":1476213212000},"page":"381-392","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":45,"title":["Precursors to suicidality and violence on antidepressants: systematic review of trials in adult healthy volunteers"],"prefix":"10.1177","volume":"109","author":[{"given":"Andreas \u00d8","family":"Bielefeldt","sequence":"first","affiliation":[{"name":"Nordic Cochrane Centre, Rigshospitalet, 2100 Copenhagen \u00d8, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pia B","family":"Danborg","sequence":"additional","affiliation":[{"name":"Nordic Cochrane Centre, Rigshospitalet, 2100 Copenhagen \u00d8, Denmark"},{"name":"Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen N, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter C","family":"G\u00f8tzsche","sequence":"additional","affiliation":[{"name":"Nordic Cochrane Centre, Rigshospitalet, 2100 Copenhagen \u00d8, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2016,10,11]]},"reference":[{"key":"bibr1-0141076816666805","doi-asserted-by":"publisher","DOI":"10.1186\/1472-6904-1-3"},{"key":"bibr2-0141076816666805","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2014-005535"},{"key":"bibr3-0141076816666805","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.g3510"},{"key":"bibr4-0141076816666805","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.g3555"},{"key":"bibr5-0141076816666805","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.i65"},{"key":"bibr6-0141076816666805","doi-asserted-by":"publisher","DOI":"10.3109\/08039480903511381"},{"key":"bibr7-0141076816666805","volume-title":"Let Them Eat Prozac: The Unhealthy Relationship Between the Pharmaceutical Industry and Depression","author":"Healy D","year":"2004"},{"key":"bibr8-0141076816666805","volume-title":"Medicines Out of Control? Antidepressants and the Conspiracy of Goodwill","author":"Medawar C","year":"2004"},{"key":"bibr9-0141076816666805","volume-title":"Anatomy of an Epidemic","author":"Whitaker R","year":"2010"},{"key":"bibr10-0141076816666805","volume-title":"Deadly Psychiatry and Organised Denial","author":"G\u00f8tzsche PC","year":"2015"},{"key":"bibr11-0141076816666805","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2012.07.004"},{"key":"bibr12-0141076816666805","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.b2880"},{"key":"bibr13-0141076816666805","unstructured":"FDA.\n                      Revisions to Product Labeling\n                      . See http:\/\/www.fda.gov\/downloads\/Drugs\/DrugSafety\/InformationbyDrugClass\/UCM173233.pdf (last checked 2 September 2016)."},{"key":"bibr14-0141076816666805","doi-asserted-by":"publisher","DOI":"10.1192\/bjp.bp.107.048371"},{"key":"bibr15-0141076816666805","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0015337"},{"key":"bibr16-0141076816666805","doi-asserted-by":"publisher","DOI":"10.1192\/bjp.bp.108.051110"},{"key":"bibr17-0141076816666805","first-page":"31","volume":"16","author":"Breggin PR","year":"2003","journal-title":"Int J Risk Saf Med"},{"key":"bibr18-0141076816666805","doi-asserted-by":"publisher","DOI":"10.1080\/00332747.1998.11024833"},{"key":"bibr19-0141076816666805","unstructured":"Higgins JP and Green S, eds. Methods for incorporating cross-over trials into a meta-analysis. In:\n                      Cochrane Handbook for Systematic Reviews of Interventions\n                      . The Cochrane Collaboration 2011."},{"key":"bibr20-0141076816666805","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/31.1.140"},{"key":"bibr21-0141076816666805","doi-asserted-by":"publisher","DOI":"10.1176\/ps.2009.60.3.384"},{"key":"bibr22-0141076816666805","unstructured":"Jacobs DG, Baldessarini RJ, Conwell Y, Fawcett JA, Horton L and Meltzer H et al. Practice guideline for the assessment and treatment of patients with suicidal behaviors. American Psychiatric Association, 2003."},{"key":"bibr23-0141076816666805","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.0030372"},{"key":"bibr24-0141076816666805","first-page":"65","volume":"4","author":"Lucire Y","year":"2011","journal-title":"Pharmgenomics Pers Med"},{"key":"bibr25-0141076816666805","doi-asserted-by":"publisher","DOI":"10.1185\/135525700543163"},{"key":"bibr26-0141076816666805","unstructured":"Lenzer J. Drug secrets: What the FDA isn\u2019t telling.\n                      Slate\n                      2005 September 27, http:\/\/www.slate.com\/articles\/health_and_science\/medical_examiner\/2005\/09\/drug_secrets.html."},{"key":"bibr27-0141076816666805","first-page":"5","volume":"16","author":"Medawar C","year":"2003","journal-title":"Int J Risk Saf Med"},{"key":"bibr28-0141076816666805","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.330.7488.396"},{"key":"bibr29-0141076816666805","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.330.7488.385"},{"key":"bibr30-0141076816666805","unstructured":"Laughren TP.\n                      Overview for December 13 Meeting of Psychopharmacologic Drugs Advisory Committee (PDAC)\n                      . See www.fda.gov\/ohrms\/dockets\/ac\/06\/briefing\/2006-4272b1-01-FDA.pdf (last checked 2 September 2016)."}],"container-title":["Journal of the Royal Society of Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/0141076816666805","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/0141076816666805","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/0141076816666805","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T05:11:16Z","timestamp":1777525876000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/0141076816666805"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,10]]},"references-count":30,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2016,10]]}},"alternative-id":["10.1177\/0141076816666805"],"URL":"https:\/\/doi.org\/10.1177\/0141076816666805","relation":{},"ISSN":["0141-0768","1758-1095"],"issn-type":[{"value":"0141-0768","type":"print"},{"value":"1758-1095","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,10]]}}}