title: Antidepressants and risks of suicide and suicide attempts: a 27-year observational study.
abstract: OBJECTIVE
  The 2007 revision of the black box warning for suicidality with antidepressants states that patients of all ages who initiate antidepressants should be monitored for clinical worsening or suicidality. The objective of this study was to examine the association of antidepressants with suicide attempts and with suicide deaths.
  
  
  METHODS
  A longitudinal, observational study of mood disorders with prospective assessments for up to 27 years was conducted at 5 US academic medical centers. The study sample included 757 participants who enrolled from 1979 to 1981 during an episode of mania, depression, or schizoaffective disorder, each based on Research Diagnostic Criteria. Unlike randomized controlled clinical trials of antidepressants, the analyses included participants with psychiatric and other medical comorbidity and those receiving acute or maintenance therapy, polypharmacy, or no psychopharmacologic treatment at all. Over follow-up, these participants had 6,716 time periods that were classified as either exposed to an antidepressant or not exposed. Propensity score-adjusted mixed-effects survival analyses were used to examine risk of suicide attempt or suicide, the primary outcome.
  
  
  RESULTS
  The propensity model showed that antidepressant therapy was significantly more likely when participants' symptom severity was greater (odds ratio [OR] = 1.16; 95% CI, 1.12-1.21; z = 8.22; P < .001) or when it was worsening (OR = 1.69; 95% CI, 1.50-1.89; z = 9.02; P < .001). Quintile-stratified, propensity-adjusted safety analyses using mixed-effects grouped-time survival models indicate that the risk of suicide attempts or suicides was reduced by 20% among participants taking antidepressants (hazard ratio, 0.80; 95% CI, 0.68-0.95; z = -2.54; P = .011).
  
  
  CONCLUSIONS
  This longitudinal study of a broadly generalizable cohort found that, although those with more severe affective syndromes were more likely to initiate treatment, antidepressants were associated with a significant reduction in the risk of suicidal behavior. Nonetheless, we believe that clinicians must closely monitor patients when an antidepressant is initiated.
authors.affiliation: Department of Psychiatry, Weill Cornell Medical College, New York, NY 10065, USA. acleon@med.cornell.edu
authors.forename: Andrew C
authors.initials: AC
authors.lastname: Leon
authors.forename: David A
authors.initials: DA
authors.lastname: Solomon
authors.forename: Chunshan
authors.initials: C
authors.lastname: Li
authors.forename: Jess G
authors.initials: JG
authors.lastname: Fiedorowicz
authors.forename: W H
authors.initials: WH
authors.lastname: Coryell
authors.forename: Jean
authors.initials: J
authors.lastname: Endicott
authors.forename: Martin B
authors.initials: MB
authors.lastname: Keller
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000928:Antidepressive Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001714:Bipolar Disorder / Q000188:drug therapy / Q000523:psychology; D016001:Confidence Intervals; D003866:Depressive Disorder / Q000188:drug therapy / Q000523:psychology; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D057216:Propensity Score; D011569:Psychiatric Status Rating Scales; D011618:Psychotic Disorders / Q000188:drug therapy / Q000523:psychology; D012307:Risk Factors; D013405:Suicide / Q000523:psychology / Q000706:statistics & numerical data*; D013406:Suicide, Attempted / Q000523:psychology / Q000706:statistics & numerical data*; D055815:Young Adult
chemical_list: D000928:Antidepressive Agents