A randomized, placebo-controlled 12-month trial of divalproex and lithium in treatment of outpatients with bipolar I disorder

Charles L. Bowden, Joseph R. Calabrese, Susan L. McElroy, Laszlo Gyulai, Adel Wassef, Frederick Petty, Harrison G. Pope, James C.Y. Chou, Paul E. Keck, Linda J. Rhodes, Alan C. Swann, Robert M.A. Hirschfeld, Patricia J. Wozniak

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602 Scopus citations

Abstract

Background: Long-term outcomes are often poor in patients with bipolar disorder despite treatment; more effective treatments are needed to reduce recurrences and morbidity. This study compared the efficacy of divalproex, lithium, and placebo as prophylactic therapy. Methods: A randomized, double- blind, parallel-group multicenter study of treatment outcomes was conducted over a 52-week maintenance period. Patients who met the recovery criteria within 3 months of the onset of an index manic episode (n = 372) were randomized to maintenance treatment with divalproex, lithium, or placebo in a 2:1:1 ratio. Psychotropic medications were discontinued before randomization, except for open-label divalproex or lithium, which were gradually tapered over the first 2 weeks of maintenance treatment. The primary outcome measure was time to recurrence of any mood episode. Secondary measures were time to a manic episode, time to a depressive episode, average change from baseline in Schedule for Affective Disorders and Schizophrenia-Change Version subscale scores for depression and mania, and Global Assessment of Function scores. Results: The divalproex group did not differ significantly from the placebo group in time to any mood episode. Divalproex was superior to placebo in terms of lower rates of discontinuation for either a recurrent mood episode or depressive episode. Divalproex was superior to lithium in longer-duration of successful prophylaxis in the study and less deterioration in depressive symptoms and Global Assessment Scale scores. Conclusions: The treatments did not differ significantly on time to recurrence of any mood episode during maintenance therapy. Patients treated with divalproex had better outcome than those treated with placebo or lithium on several secondary outcome measures.

Original languageEnglish (US)
Pages (from-to)481-489
Number of pages9
JournalArchives of general psychiatry
Volume57
Issue number5
DOIs
StatePublished - May 2000

ASJC Scopus subject areas

  • Arts and Humanities (miscellaneous)
  • Psychiatry and Mental health

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    Bowden, C. L., Calabrese, J. R., McElroy, S. L., Gyulai, L., Wassef, A., Petty, F., Pope, H. G., Chou, J. C. Y., Keck, P. E., Rhodes, L. J., Swann, A. C., Hirschfeld, R. M. A., & Wozniak, P. J. (2000). A randomized, placebo-controlled 12-month trial of divalproex and lithium in treatment of outpatients with bipolar I disorder. Archives of general psychiatry, 57(5), 481-489. https://doi.org/10.1001/archpsyc.57.5.481