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Suicide Risk Lower Among Bipolar Disorder Patients Using Lithium Compared with Divalproex

Suicide attempts and suicide death rates are lower among patients treated with lithium than among those treated with divalproex for bipolar disorder according to the findings of a retrospective study of participants in 2 integrated health plans in California and Washington, United States.

"In this population-based sample of more than 20,000 persons treated for bipolar disorder, we found that risk of suicide attempt or suicide death was 1.5 to 3 times higher during periods of treatment with divalproex and during periods of treatment with lithium," writes Frederick K. Goodwin, MD, George Washington University Medical Center, Washington, DC and colleagues. They identified suicide mortality, suicide attempts resulting in hospitalization, and suicide attempts resulting in visits to a hospital emergency department but not requiring admission among 20,638 participants treated for bipolar disorder between the beginning of 1994 and the end of 2001. The cohort was predominantly female and younger than 45 years of age.

The investigators identified 53 suicides, 338 attempts that resulted in hospitalisation, and 642 attempts requiring emergency department visits among the cohort. Mean follow up was approximately 2.9 years per individual.

Unadjusted rates (per 1000 person-years) of suicide attempts with hospitalization were 10.5 for divalproex and 4.2 for lithium, suicide attempt with emergency department visit were 31.3 for divalproex and 10.8 for lithium, and for suicide death were 1.7 for divalproex and 0.7 for lithium.

The researchers then adjusted for age, sex, health plan, date of diagnosis, comorbid conditions, and concomitant psychotropic drug use and found that the risk for each of the outcomes was still significantly higher during exposure to divalproex than exposure to lithium.

Dr. Goodwin and colleagues also found that a medication switch was associated with a higher risk of suicide attempt resulting in hospitalisation, noting a hazard ratio of 2.0 when switching from lithium to divalproex and a hazard ratio of 1.8 when switching from divalproex to lithium.

"This evidence of lower suicide risk during lithium treatment should be viewed in light of the declining use of lithium by psychiatrists in the United States, particularly among recently trained psychiatrists," the authors suggest. "At the least," they conclude, "use of lithium to treat mood disorders should be an essential component of training in psychiatry."

JAMA 2003;290:11:1467-1473.

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