title: Lines of evidence on the risks of suicide with selective serotonin reuptake inhibitors.
abstract: BACKGROUND
  There has been a long-standing controversy about the possibility that selective serotonin reuptake inhibitor (SSRI) antidepressants might induce suicidality in some patients.
  
  
  METHODS
  Starting from the clinical studies that gave rise to this issue, this paper reviews an unselected cohort of randomized clinical trials (RCTs), a series of meta-analyses undertaken to investigate aspects of the problem, studies in recurrent brief depressive disorders, epidemiological studies and healthy volunteer studies using SSRIs to shed light on this issue.
  
  
  RESULTS
  The original clinical studies produced evidence of a dose-dependent link, present on a challenge, dechallenge and rechallenge basis, between SSRIs and both agitation and suicidality. Meta-analyses of RCTs conducted around this time indicate that SSRIs may reduce suicidal ideation in some patients. These same RCTs, however, yield an excess of suicides and suicide attempts on active treatments compared with placebos. This excess also appears in the best-controlled epidemiological studies. Finally, healthy volunteer studies give indications that SSRIs may induce agitation and suicidality in some individuals.
  
  
  CONCLUSIONS
  The data reviewed here, which indicate a possible doubling of the relative risk of both suicides and suicide attempts on SSRIs compared with older antidepressants or non-treatment, make it difficult to sustain a null hypothesis, i.e. that SSRIs do not cause problems in some individuals to whom they are given. Further studies or further access to data are indicated to establish the magnitude of any risk and the characteristics of patients who may be most at risk.
authors.affiliation: North Wales Department of Psychological Medicine, University of Wales College of Medicine, Bangor, UK. healy_hergest@compuserve.com
authors.forename: David
authors.initials: D
authors.lastname: Healy
mesh_terms: D000928:Antidepressive Agents / Q000009:adverse effects*; D003866:Depressive Disorder / Q000188:drug therapy* / Q000523:psychology; D006801:Humans; D012307:Risk Factors; D017367:Selective Serotonin Reuptake Inhibitors / Q000009:adverse effects*; D013405:Suicide / Q000706:statistics & numerical data
chemical_list: D000928:Antidepressive Agents; D017367:Selective Serotonin Reuptake Inhibitors