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.

BACKGROUND: Observational research frequently uses administrative codes for mental health or substance use diagnoses and for important behaviours such as suicide attempts. We sought to validate codes (International Classification of Diseases, 9th edition, clinical modification diagnostic and E-codes) entered in Veterans Health Administration administrative data for patients with depression versus a gold standard of electronic medical record text ("chart notation"). METHODS: Three random samples of patients were selected, each stratified by geographic region, gender, and year of cohort entry, from a VHA depression treatment cohort from April 1, 1999 to September 30, 2004. The first sample was selected from patients who died by suicide, the second from patients who remained alive on the date of death of suicide cases, and the third from patients with a new start of a commonly used antidepressant medication. Four variables were assessed using administrative codes in the year prior to the index date: suicide attempt, alcohol abuse/dependence, drug abuse/dependence and tobacco use. RESULTS: Specificity was high (≥ 90%) for all four administrative codes, regardless of the sample. Sensitivity was ≤75% and was particularly low for suicide attempt (≤ 17%). Positive predictive values for alcohol dependence/abuse and tobacco use were high, but barely better than flipping a coin for illicit drug abuse/dependence. Sensitivity differed across the three samples, but was highest in the suicide death sample. CONCLUSIONS: Administrative data-based diagnoses among VHA records have high specificity, but low sensitivity. The accuracy level varies by different diagnosis and by different patient subgroup.