Suicide Risk in Bipolar Disorder During Treatment With Lithium and Divalproex

CONTEXT: Several studies have suggested that lithium treatment reduces risk of suicide in bipolar disorder, but no research has examined suicide risk during treatment with divalproex, the most commonly prescribed mood-stabilizing drug in the United States. OBJECTIVE: To compare risk of suicide attempt and suicide death during treatment with lithium with that during treatment with divalproex. DESIGN AND SETTING: Retrospective cohort study conducted at 2 large integrated health plans in California and Washington. PATIENTS: Population-based sample of 20 638 health plan members aged 14 years or older who had at least 1 outpatient diagnosis of bipolar disorder and at least 1 filled prescription for lithium, divalproex, or carbamazepine between January 1, 1994, and December 31, 2001. Follow-up for each individual began with first qualifying prescription and ended with death, disenrollment from the health plan, or end of the study period. MAIN OUTCOME MEASURES: Suicide attempt, recorded as a hospital discharge diagnosis or an emergency department diagnosis; suicide death, recorded on death certificate. RESULTS: In both health plans, unadjusted rates were greater during treatment with divalproex than during treatment with lithium for emergency department suicide attempt (31.3 vs 10.8 per 1000 person-years; P<.001), suicide attempt resulting in hospitalization (10.5 vs 4.2 per 1000 person-years; P<.001), and suicide death (1.7 vs 0.7 per 1000 person-years; P =.04). After adjustment for age, sex, health plan, year of diagnosis, comorbid medical and psychiatric conditions, and concomitant use of other psychotropic drugs, risk of suicide death was 2.7 times higher (95% confidence interval CI, 1.1-6.3; P =.03) during treatment with divalproex than during treatment with lithium. Corresponding hazard ratios for nonfatal attempts were 1.7 (95% CI, 1.2-2.3; P =.002) for attempts resulting in hospitalization and 1.8 (95% CI, 1.4-2.2; P<.001) for attempts diagnosed in the emergency department. CONCLUSION: Among patients treated for bipolar disorder, risk of suicide attempt and suicide death is lower during treatment with lithium than during treatment with divalproex.