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Frederick K. Goodwin, MD; Bruce Fireman, MA; Gregory E. Simon, MD; Enid M. Hunkeler, MA; Janelle Lee, MHA, DrPH; Dennis Revicki, PhD

JAMA. 2003;290:1467-1473.

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.

Author Affiliations: Department of Psychiatry, George Washington University Medical Center, Washington, DC (Dr Goodwin); Best Practice LLC (Dr Goodwin) and Center for Health Outcomes Research, MEDTAP International (Dr Revicki), Bethesda, Md; Division of Research, Kaiser Permanente Medical Care Program, Oakland, Calif (Mr Fireman, Ms Hunkeler, and Dr Lee); Center for Health Studies, Group Health Cooperative, Seattle, Wash (Dr Simon).

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