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Valproate for the treatment of acute bipolar depression: systematic review and meta-analysis

By L.A. Smith, V.R. Cornelius, J.M. Azorin, G. Perugi, E. Vieta, A.H. Young and C.L. Bowden


Background: Our aim was to analyse existing data on the efficacy and tolerability of valproate<br/>for the treatment of acute bipolar depression.<br/><br/>Methods: Randomized controlled trials comparing valproate with placebo were identified using<br/>searches of electronic databases in October 2008. Outcomes investigated were depression,<br/>anxiety, hypomania, attrition, and adverse events. Trial quality was assessed, and data were<br/>summarized using meta-analyses.<br/><br/>Results: Four randomized, controlled, doubleblind trials of 142 participants were included. Trial<br/>quality was good, although individual study sample sizes were small. Study duration was six<br/>weeks (2 studies) and eight weeks (2 studies). Meta-analysis showed a significant difference in<br/>favour of valproate for reduction in depressive symptoms, both on depression symptom scales<br/>(standardized mean difference (SMD) ?0.35 (95% confidence interval, ?0.69, ?0.02)), and<br/>participants with at least 50% improvement in symptoms — relative risk (RR) 2.00 (1.13, 3.53).<br/>Effects on anxiety symptoms were small,SMD?0.32 (?0.72, 0.08) and inconclusive (p=0.12).<br/>No evidence of a difference in mania symptoms, withdrawal for any reason, lack of effectiveness<br/>or adverse events was detected. Nausea occurred more frequently with valproate compared<br/>with placebo though the difference was not significant, RR 2.01 (0.98, 4.11). Other adverse<br/>events occurring more frequently with valproate (somnolence, fatigue/muscle weakness,<br/>headache, diarrhoea and dry mouth) did not differ significantly between treatment groups.<br/><br/>Limitations: Sample sizes were small warranting a larger study to confirm or disprove these<br/>findings.<br/><br/>Conclusions: Valproate is effective for the reduction of depressive symptoms of acute bipolar<br/>depression, and was well tolerated

Topics: RC0321, RM
Year: 2010
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Provided by: e-Prints Soton
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