Valproate for schizophrenia.Cochrane Database Syst Rev. 2008 Jul 16CD
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; valproate is one of these.
To review the effects of valproate for the treatment of schizophrenia and schizophrenia-like psychoses.
We searched the Cochrane Schizophrenia Group's register (last update February 2007). This register is compiled by 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.
We included 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
We independently inspected citations and, where possible, abstracts, ordered papers and re-inspected and quality assessed these. Data were extracted independently by at least two reviewers. We analysed dichotomous data using relative risks (RR) and the 95% confidence intervals (CI). We analysed continuous data using weighted mean differences. Where possible we calculated the number needed to treat (NNT) or number needed to harm statistics.
The update search identified two further relevant studies, thus the review currently includes seven studies with a total of 519 participants. 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 (6 RCT, n=270, RR leaving the study early 1.7 CI 0.9 to 3.2). No significant effect of valproate as an adjunct to antipsychotic medication on the participants' global state or the general mental state at the endpoint was evident. However, one study showed a quicker onset of action in the combination group (Casey 2003). A single small study found the participants in the valproate group to be less aggressive than the control group (n=30, WMD -3.8, CI -5.1 to -2.5). Participants receiving valproate more frequently experienced sedation than those in the placebo group. In a single small study valproate significantly reduced tardive dyskinesia (n=30, WMD -3.3, CI -4.9 to -1.7). The effects of valproate on important subgroups such as those with schizophrenia and aggressive behaviour or those with schizoaffective disorder are unknown.