title: Precursors to suicidality and violence on antidepressants: systematic review of trials in adult healthy volunteers.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  Systematic review and meta-analysis.
  
  
  METHODS
  Harms related to suicidality, hostility, activation events, psychotic events and mood disturbances.
  
  
  METHODS
  Published trials identified by searching PubMed and Embase and clinical study reports obtained from the European and UK drug regulators.
  
  
  METHODS
  Double-blind, placebo-controlled trials in adult healthy volunteers that reported on suicidality or violence or precursor events to suicidality or violence.
  
  
  RESULTS
  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 = 0.02, I2= 18%). 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.
  
  
  CONCLUSIONS
  Antidepressants double the occurrence of events in adult healthy volunteers that can lead to suicide and violence.
authors.affiliation: Nordic Cochrane Centre, Rigshospitalet, 2100 Copenhagen Ø, Denmark.
authors.forename: Andreas Ø
authors.initials: AØ
authors.lastname: Bielefeldt
authors.affiliation: Nordic Cochrane Centre, Rigshospitalet, 2100 Copenhagen Ø, Denmark Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen N, Denmark.
authors.forename: Pia B
authors.initials: PB
authors.lastname: Danborg
authors.affiliation: Nordic Cochrane Centre, Rigshospitalet, 2100 Copenhagen Ø, Denmark pcg@cochrane.dk.
authors.forename: Peter C
authors.initials: PC
authors.lastname: Gøtzsche
mesh_terms: D000328:Adult; D000928:Antidepressive Agents / Q000009:adverse effects*; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D008297:Male; D012306:Risk; D017367:Selective Serotonin Reuptake Inhibitors / Q000009:adverse effects*; D000068760:Serotonin and Noradrenaline Reuptake Inhibitors / Q000009:adverse effects*; D013405:Suicide; D014754:Violence
chemical_list: D000928:Antidepressive Agents; D017367:Selective Serotonin Reuptake Inhibitors; D000068760:Serotonin and Noradrenaline Reuptake Inhibitors
keywords: Psychiatry; antidepressants; depression; healthy volunteers