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.
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.
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.
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
Among patients treated for bipolar disorder, risk of suicide attempt
and suicide death is lower during treatment with lithium than during treatment