Valproate for acute mood episodes in bipolar disorder

Background

Valproate has become a leading adjunctive and alternative treatment to lithium in bipolar disorder.

Objectives

To determine the efficacy and acceptability of valproate in acute episodes of bipolar disorder.

Search strategy

Registers and databases:

Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Registrar (version 2-2002)
Cochrane Controlled Clinical Trials Register (3-2002)
Medline (1966-January 1999 )
PsychLit (1996-June 1999)
Embase (1980-January 1999)

Reference lists of relevant papers/books.

Trial authors, experts and pharmaceutical companies.

Handsearches (specialist journals and conference proceedings, listed below)

Selection criteria

Randomised controlled trials comparing valproate with placebo and other medications for any acute episode. Bipolar patients, male and female, of all ages were included.

Data collection and analysis

Data extraction and methodological quality assessment were each performed independently by two reviewers. For analysis, relative risk was used for binary efficacy outcomes and the weighted mean difference or standardised mean difference used for continuously distributed outcomes.

Main results

Ten trials compared valproate with other interventions in mania. None examined depression or mixed affective episodes. Data were extracted on 'failure to respond by the end of the study' (i.e.less than 50% reduction in Young Mania Rating Scale or SADS-S mania scale). Three trials (316 participants) compared valproate with placebo. Three trials (158 participants) compared valproate with lithium. Two trials (363 participants) compared valproate with olanzapine. One trial (36 participants) compared valproate with haloperidol. Two trials (59 patients) compared valproate with carbamazepine.

Treatment acceptability was estimated by the 'total number withdrawing from the study'. Three trials (321 patients) compared valproate and placebo, two (144 patients) compared valproate with lithium. One study (30 patients) compared valproate and carbamazepine. Pooled relative risks ( 95% confidence intervals) were calculated using fixed effect.

Valproate was more efficacious than placebo (RRR 38%; RR 0.62; 95% C.I. 0.51 to 0.77) in the treatment of mania. There was no significant difference between valproate and lithium (RRI 5%; RR 1.05; 95% C.I. 0.74-1.50) or between valproate and carbamazepine (RRR 34%; RR 0.66; 95% C.I. 0.38 to 1.16). Valproate was less effective than olanzapine (failure to achieve clinical response; RRI 25%; RR 1.25, 95% C.I. 1.01 to 1.54; average of 2.8 point less change on the Mania Rating Scale (95% CI 0.83 to 4.79). There were no significant differences in those withdrawing from the study.

Authors' conclusions

There is consistent, if limited, evidence that valproate is an efficacious treatment for acute mania. Valproate may be less efficacious than olanzapine. More, rigorously designed, trials over the full range of acute affective episodes are required.