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Valproate for schizophrenia.

Abstract

BACKGROUND

Many people with schizophrenia do not achieve a satisfactory treatment response with ordinary antipsychotic drug treatment. In these cases, various add-on medications are used, among them valproate.

OBJECTIVES

To review the effects of valproate for the treatment of schizophrenia and schizophrenia-like psychoses.

SEARCH STRATEGY

The reviewers searched the Cochrane Schizophrenia Group's register (July 2002). This register is compiled of methodical searches of BIOSIS, CINAHL, Dissertation abstracts, EMBASE, LILACS, MEDLINE, PSYNDEX, PsycINFO, RUSSMED, Sociofile, supplemented with hand searching of relevant journals and numerous conference proceedings. We also contacted a pharmaceutical company and authors of relevant studies in order to identify further trials.

SELECTION CRITERIA

All randomised controlled trials comparing valproate to antipsychotics or to placebo (or no intervention), whether as the sole agent or as an adjunct to antipsychotic medication for the treatment of schizophrenia and/or schizophrenia-like psychoses.

DATA COLLECTION AND ANALYSIS

Citations and, where possible, abstracts were independently inspected by reviewers, papers ordered, re-inspected and quality assessed. Data were extracted independently by at least two reviewers. Dichotomous data were analysed using relative risks (RR) and the 95% confidence intervals (CI). Continuous data were analysed using weighted mean differences. Where possible the number needed to treat (NNT) or number needed to harm statistics were calculated.

MAIN RESULTS

Five studies with a total of 379 participants were included. All trials examined the effectiveness of valproate as an adjunct to antipsychotics. With one exception the studies were small, short-term and incompletely reported. Adding valproate was as acceptable as adding placebo to antipsychotic drugs (n=130, RR leaving the study early 1.6 CI 0.8 to 3.1). No significant effect of using valproate as an adjunct to antipsychotic medication on the participants' global state or general mental state at the endpoint studies was evident. However, one study showed a quicker onset of action in the combination group. Participants receiving valproate more frequently experienced sedation than those in the placebo group. The effects of valproate on important subgroups such as those with schizophrenia and aggressive behaviour or those with schizoaffective disorder are unknown.

REVIEWER'S CONCLUSIONS

Based on randomised trial-derived evidence which is currently available, there are no data to support or to refute the use of valproate as a sole agent for schizophrenia. There is some evidence for a more rapid improvement with valproate augmentation, but this effect vanished over time. Given this limited evidence, further large, simple well-designed and reported trials are necessary. These might focus on people with schizophrenia and violent episodes, on those with treatment resistant forms of the disorder and on people with schizoaffective disorders.

Authors+Show Affiliations

Psychiatrische Klinik und Poliklinik der Technischen Universität München, Klinikum rechts der Isar, Ismaninger Str. 22, München, Germany.No affiliation info available

Pub Type(s)

Journal Article
Meta-Analysis
Review
Systematic Review

Language

eng

PubMed ID

14974054

Citation

Basan, A, and S Leucht. "Valproate for Schizophrenia." The Cochrane Database of Systematic Reviews, 2004, p. CD004028.
Basan A, Leucht S. Valproate for schizophrenia. Cochrane Database Syst Rev. 2004.
Basan, A., & Leucht, S. (2004). Valproate for schizophrenia. The Cochrane Database of Systematic Reviews, (1), CD004028.
Basan A, Leucht S. Valproate for Schizophrenia. Cochrane Database Syst Rev. 2004;(1)CD004028. PubMed PMID: 14974054.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Valproate for schizophrenia. AU - Basan,A, AU - Leucht,S, PY - 2004/2/20/pubmed PY - 2004/6/30/medline PY - 2004/2/20/entrez SP - CD004028 EP - CD004028 JF - The Cochrane database of systematic reviews JO - Cochrane Database Syst Rev IS - 1 N2 - BACKGROUND: Many people with schizophrenia do not achieve a satisfactory treatment response with ordinary antipsychotic drug treatment. In these cases, various add-on medications are used, among them valproate. OBJECTIVES: To review the effects of valproate for the treatment of schizophrenia and schizophrenia-like psychoses. SEARCH STRATEGY: The reviewers searched the Cochrane Schizophrenia Group's register (July 2002). This register is compiled of methodical searches of BIOSIS, CINAHL, Dissertation abstracts, EMBASE, LILACS, MEDLINE, PSYNDEX, PsycINFO, RUSSMED, Sociofile, supplemented with hand searching of relevant journals and numerous conference proceedings. We also contacted a pharmaceutical company and authors of relevant studies in order to identify further trials. SELECTION CRITERIA: All randomised controlled trials comparing valproate to antipsychotics or to placebo (or no intervention), whether as the sole agent or as an adjunct to antipsychotic medication for the treatment of schizophrenia and/or schizophrenia-like psychoses. DATA COLLECTION AND ANALYSIS: Citations and, where possible, abstracts were independently inspected by reviewers, papers ordered, re-inspected and quality assessed. Data were extracted independently by at least two reviewers. Dichotomous data were analysed using relative risks (RR) and the 95% confidence intervals (CI). Continuous data were analysed using weighted mean differences. Where possible the number needed to treat (NNT) or number needed to harm statistics were calculated. MAIN RESULTS: Five studies with a total of 379 participants were included. All trials examined the effectiveness of valproate as an adjunct to antipsychotics. With one exception the studies were small, short-term and incompletely reported. Adding valproate was as acceptable as adding placebo to antipsychotic drugs (n=130, RR leaving the study early 1.6 CI 0.8 to 3.1). No significant effect of using valproate as an adjunct to antipsychotic medication on the participants' global state or general mental state at the endpoint studies was evident. However, one study showed a quicker onset of action in the combination group. Participants receiving valproate more frequently experienced sedation than those in the placebo group. The effects of valproate on important subgroups such as those with schizophrenia and aggressive behaviour or those with schizoaffective disorder are unknown. REVIEWER'S CONCLUSIONS: Based on randomised trial-derived evidence which is currently available, there are no data to support or to refute the use of valproate as a sole agent for schizophrenia. There is some evidence for a more rapid improvement with valproate augmentation, but this effect vanished over time. Given this limited evidence, further large, simple well-designed and reported trials are necessary. These might focus on people with schizophrenia and violent episodes, on those with treatment resistant forms of the disorder and on people with schizoaffective disorders. SN - 1469-493X UR - https://www.unboundmedicine.com/medline/citation/14974054/Valproate_for_schizophrenia_ DB - PRIME DP - Unbound Medicine ER -