Divalproex sodium versus placebo in the treatment of acute bipolar depression: A systematic review and meta-analysis

David J. Bond, Raymond W. Lam, Lakshmi N. Yatham

Research output: Contribution to journalReview articlepeer-review

84 Scopus citations


Background: Bipolar disorders (BDs) are defined by mania and hypomania, but depressions occur more frequently, last longer, and lead to significant disability. Divalproex is the most frequently prescribed anticonvulsant medication for BD. While some evidence suggests that divalproex prevents depressive episodes during maintenance treatment, it is not commonly used in the treatment of acute depression, and there is a perception that there is little evidence to support its efficacy. Methods: We conducted a meta-analysis of randomized placebo-controlled trials assessing the efficacy of divalproex in acute BD depression. We searched MEDLINE and the Cochrane Database of Systematic Reviews using the search terms "divalproex AND bipolar depression", "valproate AND bipolar depression", and "valproic acid AND bipolar depression". We also accessed the databases of clinical trial registries, including www.ClinicalTrials.gov, www.who.int/ictrp, http://isrctn.org, http://www.mrw.interscience.wiley.com/cochrane/cochrane_clcentral_articles_fs.html, and www.ClinicalStudyResults.org. All English-language, randomized, double-blind, placebo-controlled trials assessing the efficacy of divalproex monotherapy in the treatment of BD depression were included in the analysis. Data were subjected to meta-analysis to determine the relative risks of response and remission, and combined to estimate average response and remission rates. Results: We identified four trials, with a total sample size of 142 patients. The relative risks of response (RR = 2.10, p = 0.02) and remission (RR = 1.61, p = 0.04) were significantly greater for divalproex than placebo. Mean response rates were 39.3% for divalproex and 17.5% for placebo, and mean remission rates were 40.6% and 24.3%, respectively. Limitations: The total sample size in the four trials was small. Conclusions: These results provide preliminary evidence that divalproex is efficacious in the treatment of BD depression.

Original languageEnglish (US)
Pages (from-to)228-234
Number of pages7
JournalJournal of Affective Disorders
Issue number3
StatePublished - Aug 2010

Bibliographical note

Funding Information:
Dr. Bond has received research grants from the Canadian Institutes of Health Research and the UBC Institute of Mental Health/Coast Capital Depression Research Fund. He has received honouraria from the Canadian Network for Mood and Anxiety Treatments and Astra-Zeneca.


  • Bipolar disorder
  • Depression
  • Divalproex
  • Meta-analysis
  • Randomized controlled trial


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