title: Antiepileptic drugs for bipolar disorder and the risk of suicidal behavior: a 30-year observational study.
abstract: OBJECTIVE
  In 2009 the U.S. Food and Drug Administration issued a warning regarding suicidality and antiepileptic drugs based on meta-analyses of 199 randomized trials (over 43,000 subjects with different illnesses) of 11 antiepileptics. The present study examines the hypothesis that the three antiepileptics approved for bipolar disorder (carbamazepine, lamotrigine, and valproate) are associated with an elevated risk of suicide attempts and suicides.
  
  
  METHODS
  A prospective observational study was conducted at five U.S. academic medical centers from 1978 to 2009. Analyses included 199 participants with bipolar disorder for whom 1,077 time intervals were classified as either exposed to an antiepileptic (carbamazepine, lamotrigine, or valproate) or not exposed to an antiepileptic, an antidepressant, or lithium during 30 years of follow-up.
  
  
  RESULTS
  Participants who had more severe manic symptoms were more likely to receive antiepileptic drugs. Mixed-effects grouped-time survival models revealed no elevation in risk of suicide attempt or suicide during periods when participants were receiving antiepileptics relative to periods when they were not (hazard ratio=0.93, 95% CI=0.45-1.92), controlling for demographic and clinical variables through propensity score matching.
  
  
  CONCLUSIONS
  In this longitudinal observational study, the risk of suicide attempts or suicides was not associated with the antiepileptics approved for bipolar disorder.
authors.affiliation: Department of Psychiatry, Weill Cornell Medical College, New York, 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: William 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; D000927:Anticonvulsants / Q000009:adverse effects / Q000627:therapeutic use*; D001714:Bipolar Disorder / Q000188:drug therapy*; D002220:Carbamazepine / Q000009:adverse effects / Q000627:therapeutic use; D005260:Female; D006801:Humans; D000077213:Lamotrigine; D018020:Lithium Compounds / Q000009:adverse effects / Q000627:therapeutic use; D008297:Male; D057216:Propensity Score; D011446:Prospective Studies; D012307:Risk Factors; D013405:Suicide / Q000706:statistics & numerical data*; D013406:Suicide, Attempted / Q000706:statistics & numerical data; D014227:Triazines / Q000009:adverse effects / Q000627:therapeutic use; D014635:Valproic Acid / Q000009:adverse effects / Q000627:therapeutic use
chemical_list: D000927:Anticonvulsants; D018020:Lithium Compounds; D014227:Triazines; D002220:Carbamazepine; D014635:Valproic Acid; D000077213:Lamotrigine