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

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_cicentral_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. (C) 2009 Elsevier B.V. All rights reserved.