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Risk Of Suicide Attempt and Death Higher With Divalproex Than With Lithium In Patients With Bipolar Disorder

Among patients being treated for bipolar disorder, the risk of suicide attempts and deaths is 1.5 to 3 times higher with divalproex than with lithium treatment, say researchers.

Several studies have suggested that lithium reduces suicide risk in patients with bipolar disorder; however, the risk with divalproex, the most commonly prescribed mood-stabilizing drug in the United States, has not been examined.

Frederick K. Goodwin, MD, with Department of Psychiatry at George Washington University Medical Center, Washington, DC, and colleagues analysed data from participants in 2 large integrated health plans in California and Washington.

The population-based sample included 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.

For both health plans, unadjusted rates were significantly higher during treatment with divalproex than with lithium for emergency department suicide attempt (p < 0.001), suicide attempt resulting in hospitalisation (p < 0.001), and suicide death (p = 0.04).

After adjustment for confounding factors, risk of suicide death was 2.7 times higher (p = 0.03) during treatment with divalproex than with lithium. Corresponding hazard ratios for nonfatal attempts were 1.7 (p = 0.002) for attempts resulting in hospitalisation and 1.8 (p < 0.001) for attempts diagnosed in the emergency department.

"This difference in risk was consistent across all outcome measures...and across the 2 study sites," the authors point out. They add that results for carbamazepine were similar to those of divalproex but perhaps less precise due to the sample size.

Dr. Goodwin and colleagues point out that "many psychiatric residents have no or limited experience prescribing lithium, largely a reflection of the enormous focus on the newer drugs in educational programs supported by the pharmaceutical industry."

"If lithium does have an anti-suicide effect not matched by currently available alternatives, then current prescribing patterns should be re-evaluated," they add.
JAMA. 2003;290:1467-1473. "Suicide Risk in Bipolar Disorder During Treatment With Lithium and Divalproex"

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