title: Suicide risk in Veterans Health Administration patients with mental health diagnoses initiating lithium or valproate: a historical prospective cohort study.
abstract: BACKGROUND
  Lithium has been reported in some, but not all, studies to be associated with reduced risks of suicide death or suicidal behavior. The objective of this nonrandomized cohort study was to examine whether lithium was associated with reduced risk of suicide death in comparison to the commonly-used alternative treatment, valproate.
  
  
  METHODS
  A propensity score-matched cohort study was conducted of Veterans Health Administration patients (n=21,194/treatment) initiating lithium or valproate from 1999-2008.
  
  
  RESULTS
  Matching produced lithium and valproate treatment groups that were highly similar in all 934 propensity score covariates, including indicators of recent suicidal behavior, but recent suicidal ideation was not able to be included. In the few individuals with recently diagnosed suicidal ideation, a significant imbalance existed with suicidal ideation more prevalent at baseline among individuals initiating lithium than valproate (odds ratio (OR) 1.30, 95% CI 1.09, 1.54; p=0.003). No significant differences in suicide death were observed over 0-365 days in A) the primary intent-to-treat analysis (lithium/valproate conditional odds ratio (cOR) 1.22, 95% CI 0.82, 1.81; p=0.32); B) during receipt of initial lithium or valproate treatment (cOR 0.86, 95% CI 0.46, 1.61; p=0.63); or C) after such treatment had been discontinued/modified (OR 1.51, 95% CI 0.91, 2.50; p=0.11). Significantly increased risks of suicide death were observed after the discontinuation/modification of lithium, compared to valproate, treatment over the first 180 days (OR 2.72, 95% CI 1.21, 6.11; p=0.015).
  
  
  CONCLUSIONS
  In this somewhat distinct sample (a predominantly male Veteran sample with a broad range of psychiatric diagnoses), no significant differences in associations with suicide death were observed between lithium and valproate treatment over 365 days. The only significant difference was observed over 0-180 days: an increased risk of suicide death, among individuals discontinuing or modifying lithium, compared to valproate, treatment. This difference could reflect risks either related to lithium discontinuation or higher baseline risks among lithium recipients (i.e., confounding) that became more evident when treatment stopped. Our findings therefore support educating patients and providers about possible suicide-related risks of discontinuing lithium even shortly after treatment initiation, and the close monitoring of patients after lithium discontinuation, if feasible. If our findings include residual confounding biasing against lithium, however, as suggested by the differences observed in diagnosed suicidal ideation, then the degree of beneficial reduction in suicide death risk associated with active lithium treatment would be underestimated. Further research is urgently needed, given the lack of interventions against suicide and the uncertainties concerning the degree to which lithium may reduce suicide risk during active treatment, increase risk upon discontinuation, or both.
authors.forename: Eric G
authors.initials: EG
authors.lastname: Smith
authors.forename: Karen L
authors.initials: KL
authors.lastname: Austin
authors.forename: Hyungjin Myra
authors.initials: HM
authors.lastname: Kim
authors.forename: Donald R
authors.initials: DR
authors.lastname: Miller
authors.forename: Susan V
authors.initials: SV
authors.lastname: Eisen
authors.forename: Cindy L
authors.initials: CL
authors.lastname: Christiansen
authors.forename: Amy M
authors.initials: AM
authors.lastname: Kilbourne
authors.forename: Brian C
authors.initials: BC
authors.lastname: Sauer
authors.forename: John F
authors.initials: JF
authors.lastname: McCarthy
authors.forename: Marcia
authors.initials: M
authors.lastname: Valenstein
mesh_terms: D018692:Antimanic Agents / Q000627:therapeutic use*; D015331:Cohort Studies; D005260:Female; D006801:Humans; D018020:Lithium Compounds / Q000627:therapeutic use*; D008297:Male; D001523:Mental Disorders / Q000188:drug therapy* / Q000523:psychology; D008875:Middle Aged; D011446:Prospective Studies; D012306:Risk; D013405:Suicide / Q000523:psychology / Q000706:statistics & numerical data*; D014481:United States; D014493:United States Department of Veterans Affairs; D014635:Valproic Acid / Q000627:therapeutic use*; D014728:Veterans / Q000523:psychology; D058014:Veterans Health / Q000706:statistics & numerical data; D000092864:Suicide Prevention
chemical_list: D018692:Antimanic Agents; D018020:Lithium Compounds; D014635:Valproic Acid