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

Valproate for the treatment of acute bipolar depression: systematic review and meta-analysis
Valproate for the treatment of acute bipolar depression: systematic review and meta-analysis
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.
0165-0327
1-9
Smith, L.A.
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Cornelius, V.R.
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Azorin, J.M.
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Perugi, G.
d360e307-2cc8-4f96-b8c9-a5c84ee13b1c
Vieta, E.
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Young, A.H.
e00425ed-86f2-4669-814e-a7a749ba1e42
Bowden, C.L.
f9a05f37-6194-4320-8731-16dcfc4523c4
Smith, L.A.
00020fbe-f9df-4a16-b134-89ce040ca269
Cornelius, V.R.
5e9e6473-6583-45a0-a1af-ca80f2e879af
Azorin, J.M.
b61e0894-2ba4-4bb5-b428-c9ee761cab50
Perugi, G.
d360e307-2cc8-4f96-b8c9-a5c84ee13b1c
Vieta, E.
c44c1240-4590-4427-a171-1422576b49a1
Young, A.H.
e00425ed-86f2-4669-814e-a7a749ba1e42
Bowden, C.L.
f9a05f37-6194-4320-8731-16dcfc4523c4

Smith, L.A., Cornelius, V.R., Azorin, J.M., Perugi, G., Vieta, E., Young, A.H. and Bowden, C.L. (2010) Valproate for the treatment of acute bipolar depression: systematic review and meta-analysis. Journal of Affective Disorders, 122 (1-2), 1-9. (doi:10.1016/j.jad.2009.10.033).

Record type: Article

Abstract

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.

Text
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Published date: April 2010
Organisations: Community Clinical Sciences

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Local EPrints ID: 161959
URI: http://eprints.soton.ac.uk/id/eprint/161959
ISSN: 0165-0327
PURE UUID: a5ba6b08-a8d4-4d5e-88d6-797fbe5b9ec3

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Date deposited: 11 Aug 2010 15:52
Last modified: 14 Mar 2024 02:01

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Contributors

Author: L.A. Smith
Author: V.R. Cornelius
Author: J.M. Azorin
Author: G. Perugi
Author: E. Vieta
Author: A.H. Young
Author: C.L. Bowden

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