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Lithium versus Divalproex in Rapid-Cycling Bipolar Disorder

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Lithium versus Divalproex in Rapid-Cycling Bipolar Disorder

Post  Admin on Sun Jun 10, 2012 3:55 pm

A 20-month, double-blind, maintenance trial of lithium versus divalproex in rapid-cycling bipolar disorder.
Am J Psychiatry. 2005 Nov;162(11):2152-61.

The authors tested the hypothesis that divalproex would be more effective than lithium in the long-term management of patients with recently stabilized rapid-cycling bipolar disorder.

A 20-month, double-blind, parallel-group comparison was carried out in recently hypomanic/manic patients who had experienced a persistent bimodal response to combined treatment with lithium and divalproex. Sixty patients were randomly assigned to lithium or divalproex monotherapy in a balanced design after stratification for illness type (bipolar I versus bipolar II disorder).

- Of the 254 patients enrolled in the open-label acute stabilization phase, 76% discontinued the study prematurely:
* poor adherence: 28%;
* nonresponse: 26% [of whom 74% remained depressed and 26% remained in a hypomanic/manic/mixed episode],
* intolerable side effects: 19%
- Of the 60 patients (24%) randomly assigned to double-blind maintenance monotherapy, 53% relapsed (59% into depression and 41% into a hypomanic/manic/mixed episode), 22% completed the study, 10% had intolerable side effects, and 10% were poorly adherent.
- The rates of relapse into any mood episode for those given: Lithium (56%) versus divalproex (50%);
the rates for depressive relapse were Lithium (34%) and Divalproex (29%); and
for a hypomania/mania relapse were Lithium (19%) and Divalproex (22%).
- There were no significant differences in time to relapse.
- The proportion discontinuing prematurely because of side effects was 16% for lithium and 4% for divalproex.

The hypothesis that divalproex is more effective than lithium in the long-term management of rapid-cycling bipolar disorder is not supported by these data. Preliminary data suggest highly recurrent refractory depression may be the hallmark of rapid-cycling bipolar disorder.

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