TY - JOUR
T1 - Valproate for the treatment of acute bipolar depression
T2 - Systematic review and meta-analysis
AU - Smith, L. A.
AU - Cornelius, V. R.
AU - Azorin, J. M.
AU - Perugi, G.
AU - Vieta, E.
AU - Young, A. H.
AU - Bowden, C. L.
N1 - Funding Information:
EV has received grants and served as consultant, advisor or speaker for the following entities: Almirall, AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Forest Research Institute, Glaxo-Smith-Kline, Janssen-Cilag, Jazz, Lundbeck, Merck, Novartis, Organon, Otsuka, Pfizer, Sanofi-Aventis, Servier, Shering-Plough, the Spanish Ministry of Science and Innovation (CIBERSAM), the Seventh European Framework Programme (ENBREC), the Stanley Medical Research Institute, United Biosource Corporation, and Wyeth.
Funding Information:
CB has received grant support from Abbott, BMS, GSK, Janssen and Repligen. He has served as a consultant for Pfizer, Sanofi-Aventis and Schering.
Copyright:
Copyright 2010 Elsevier B.V., All rights reserved.
PY - 2010/4
Y1 - 2010/4
N2 - Background: Our aim was to analyse existing data on the efficacy and tolerability of valproate for the treatment of acute bipolar depression. Methods: Randomized controlled trials comparing valproate with placebo were identified using searches of electronic databases in October 2008. Outcomes investigated were depression, anxiety, hypomania, attrition, and adverse events. Trial quality was assessed, and data were summarized using meta-analyses. Results: Four randomized, controlled, doubleblind trials of 142 participants were included. Trial quality was good, although individual study sample sizes were small. Study duration was six weeks (2 studies) and eight weeks (2 studies). Meta-analysis showed a significant difference in favour of valproate for reduction in depressive symptoms, both on depression symptom scales (standardized mean difference (SMD) - 0.35 (95% confidence interval, - 0.69, - 0.02)), and participants with at least 50% improvement in symptoms - relative risk (RR) 2.00 (1.13, 3.53). Effects on anxiety symptoms were small, SMD - 0.32 (- 0.72, 0.08) and inconclusive (p = 0.12). No evidence of a difference in mania symptoms, withdrawal for any reason, lack of effectiveness or adverse events was detected. Nausea occurred more frequently with valproate compared with placebo though the difference was not significant, RR 2.01 (0.98, 4.11). Other adverse events occurring more frequently with valproate (somnolence, fatigue/muscle weakness, headache, diarrhoea and dry mouth) did not differ significantly between treatment groups. Limitations: Sample sizes were small warranting a larger study to confirm or disprove these findings. Conclusions: Valproate is effective for the reduction of depressive symptoms of acute bipolar depression, and was well tolerated.
AB - Background: Our aim was to analyse existing data on the efficacy and tolerability of valproate for the treatment of acute bipolar depression. Methods: Randomized controlled trials comparing valproate with placebo were identified using searches of electronic databases in October 2008. Outcomes investigated were depression, anxiety, hypomania, attrition, and adverse events. Trial quality was assessed, and data were summarized using meta-analyses. Results: Four randomized, controlled, doubleblind trials of 142 participants were included. Trial quality was good, although individual study sample sizes were small. Study duration was six weeks (2 studies) and eight weeks (2 studies). Meta-analysis showed a significant difference in favour of valproate for reduction in depressive symptoms, both on depression symptom scales (standardized mean difference (SMD) - 0.35 (95% confidence interval, - 0.69, - 0.02)), and participants with at least 50% improvement in symptoms - relative risk (RR) 2.00 (1.13, 3.53). Effects on anxiety symptoms were small, SMD - 0.32 (- 0.72, 0.08) and inconclusive (p = 0.12). No evidence of a difference in mania symptoms, withdrawal for any reason, lack of effectiveness or adverse events was detected. Nausea occurred more frequently with valproate compared with placebo though the difference was not significant, RR 2.01 (0.98, 4.11). Other adverse events occurring more frequently with valproate (somnolence, fatigue/muscle weakness, headache, diarrhoea and dry mouth) did not differ significantly between treatment groups. Limitations: Sample sizes were small warranting a larger study to confirm or disprove these findings. Conclusions: Valproate is effective for the reduction of depressive symptoms of acute bipolar depression, and was well tolerated.
KW - Bipolar depression
KW - Efficacy
KW - Meta-analysis
KW - Systematic review
KW - Tolerability
KW - Valproate
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U2 - 10.1016/j.jad.2009.10.033
DO - 10.1016/j.jad.2009.10.033
M3 - Review article
C2 - 19926140
AN - SCOPUS:77649340367
VL - 122
SP - 1
EP - 9
JO - Journal of Affective Disorders
JF - Journal of Affective Disorders
SN - 0165-0327
IS - 1-2
ER -