Maintenance efficacy of divalproex in the prevention of bipolar depression

Laszlo Gyulai, Charles L. Bowden, Susan L. McElroy, Joseph R. Calabrese, Frederick Petty, Alan C. Swann, James C Y Chou, Adel Wassef, Craig S. Risch, Robert M A Hirschfeld, Charles B. Nemeroff, Paul E. Keck, Dwight L. Evans, Patricia J. Wozniak

Research output: Contribution to journalArticle

143 Citations (Scopus)

Abstract

Breakthrough depression is a common problem in the treatment of bipolar disorder. Only one, recently published, double-blind, placebo-controlled trial has examined the efficacy of divalproex in the prevention of depressive episodes in bipolar patients. This report describes, in further detail, the findings from that trial of the effect of divalproex on multiple dimensions of depressive morbidity in bipolar disorder. A randomized, double-blind, parallel-group, multicenter study was conducted over a 52-week maintenance period. Bipolar I patients, who may have been treated with open-label lithium or divalproex and who met recovery criteria within 3 months of onset of an index manic episode, were randomized to maintenance treatment with divalproex, lithium, or placebo in a 2:1:1 ratio. Adjunctive paroxetine or sertraline for breakthrough depression was allowed in maintenance phase. Outcome measures were the rate of early discontinuation for depression, time to depressive relapse, proportion of patients with depressive relapse, mean change in Depressive Syndrome Scale score, proportion of patients receiving antidepressants, and time in the study. Among patients taking an antidepressant, a higher percentage of patients on placebo than divalproex discontinued early for depression. Patients who were previously hospitalized for affective episodes or took divalproex in the open period relapsed later on divalproex than on lithium during the maintenance period. Divalproex-treated patients had less worsening of depressive symptoms than lithium-treated patients during maintenance. Indices of severity of prestudy illness course predicted worse outcome in all treatment groups. Divalproex improved several dimensions of depressive morbidity and reduced the probability of depressive relapse in bipolar disorder, particularly in patients who had responded to divabroex when manic, and among patients with a more severe course of illness.

Original languageEnglish (US)
Pages (from-to)1374-1382
Number of pages9
JournalNeuropsychopharmacology
Volume28
Issue number7
DOIs
StatePublished - Jul 2003

Fingerprint

Valproic Acid
Bipolar Disorder
Maintenance
Lithium
Depression
Placebos
Recurrence
Antidepressive Agents
Severity of Illness Index
Morbidity
Sertraline
Paroxetine
Depressive Disorder
Multicenter Studies
Therapeutics
Outcome Assessment (Health Care)

Keywords

  • Bipolar depression
  • Bipolar disorder
  • Divalproex
  • Maintenance treatment
  • Selective serotonin uptake inhibitor (SSRI)
  • Valproic acid

ASJC Scopus subject areas

  • Pharmacology

Cite this

Gyulai, L., Bowden, C. L., McElroy, S. L., Calabrese, J. R., Petty, F., Swann, A. C., ... Wozniak, P. J. (2003). Maintenance efficacy of divalproex in the prevention of bipolar depression. Neuropsychopharmacology, 28(7), 1374-1382. https://doi.org/10.1038/sj.npp.1300190

Maintenance efficacy of divalproex in the prevention of bipolar depression. / Gyulai, Laszlo; Bowden, Charles L.; McElroy, Susan L.; Calabrese, Joseph R.; Petty, Frederick; Swann, Alan C.; Chou, James C Y; Wassef, Adel; Risch, Craig S.; Hirschfeld, Robert M A; Nemeroff, Charles B.; Keck, Paul E.; Evans, Dwight L.; Wozniak, Patricia J.

In: Neuropsychopharmacology, Vol. 28, No. 7, 07.2003, p. 1374-1382.

Research output: Contribution to journalArticle

Gyulai, L, Bowden, CL, McElroy, SL, Calabrese, JR, Petty, F, Swann, AC, Chou, JCY, Wassef, A, Risch, CS, Hirschfeld, RMA, Nemeroff, CB, Keck, PE, Evans, DL & Wozniak, PJ 2003, 'Maintenance efficacy of divalproex in the prevention of bipolar depression', Neuropsychopharmacology, vol. 28, no. 7, pp. 1374-1382. https://doi.org/10.1038/sj.npp.1300190
Gyulai L, Bowden CL, McElroy SL, Calabrese JR, Petty F, Swann AC et al. Maintenance efficacy of divalproex in the prevention of bipolar depression. Neuropsychopharmacology. 2003 Jul;28(7):1374-1382. https://doi.org/10.1038/sj.npp.1300190
Gyulai, Laszlo ; Bowden, Charles L. ; McElroy, Susan L. ; Calabrese, Joseph R. ; Petty, Frederick ; Swann, Alan C. ; Chou, James C Y ; Wassef, Adel ; Risch, Craig S. ; Hirschfeld, Robert M A ; Nemeroff, Charles B. ; Keck, Paul E. ; Evans, Dwight L. ; Wozniak, Patricia J. / Maintenance efficacy of divalproex in the prevention of bipolar depression. In: Neuropsychopharmacology. 2003 ; Vol. 28, No. 7. pp. 1374-1382.
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