Carbamazepine for schizophrenia

Leucht S, Kissling W, McGrath J, White P

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Summary

Carbamazepine for schizophrenia

Carbamazepine is an antiepileptic drug, which is also used as an adjunct to antipsychotics for schizophrenia. Although the original patient data from eight out of ten included studies could be re-analysed, we found no significant benefit of carbamazepine, either as a sole treatment or as an adjunct to antipsychotics. However, as the total number of patients included was small, further randomised trials seem to be warranted.

This is a Cochrane review abstract and plain language summary, prepared and maintained by The Cochrane Collaboration, currently published in The Cochrane Database of Systematic Reviews 2009 Issue 4, Copyright © 2009 The Cochrane Collaboration. Published by John Wiley and Sons, Ltd.. The full text of the review is available in The Cochrane Library (ISSN 1464-780X).
This record should be cited as: Leucht S, Kissling W, McGrath J, White P. Carbamazepine for schizophrenia. Cochrane Database of Systematic Reviews 2007, Issue 3. Art. No.: CD001258. DOI: 10.1002/14651858.CD001258.pub2.

This version first published online: October 25. 1999
Last assessed as up-to-date: May 21. 2007

Abstract

Background

Many people with schizophrenia do not achieve a satisfactory treatment response with just antipsychotic drug treatment and various adjunct medications are used to promote additional response. The antiepileptic carbamazepine is one such drug.

Objectives

To evaluate the effects of carbamazepine and its derivatives for the treatment of schizophrenia and related psychoses.

Search strategy

For the original version we searched Biological Abstracts (1980-2001), The Cochrane Library (Issue 3, 2001), The Cochrane Schizophrenia Group's Register of Trials (December 2001), EMBASE (1980-2001), MEDLINE (1966-2001), PsycLIT (1886-2001) and PSYNDEX (1974-2001). For the current update we searched the Cochrane Schizophrenia Group's Register of Trials in March 2005 and in December 2006. We also inspected references of all identified studies for further trials and contacted relevant pharmaceutical companies and authors for additional data.

Selection criteria

We included all randomised controlled trials comparing carbamazepine or compounds of the carbamazepine family to placebo or no intervention, whether as sole treatment or as an adjunct to antipsychotic medication for the treatment of schizophrenia and/or schizoaffective psychoses.

Data collection and analysis

We extracted data independently. For homogenous dichotomous data we calculated random effects, relative risk (RR), 95% confidence intervals (CI) and, where appropriate, numbers needed to treat (NNT) on an intention-to-treat basis. For continuous data, we calculated weighted mean differences (WMD).

Main results

The update search did not reveal any further studies that met our inclusion criteria. The number of included studies therefore remains at ten with the number of participants randomised still 258. One study comparing carbamazepine with placebo as the sole treatment for schizophrenia was abandoned early due to high relapse rate with 26 out of 31 participants relapsing by three months. No effect of carbamazepine was evident with no difference in relapse between the two groups (1 RCT n=31, RR 4.1 CI 0.8 to 1.5).
Another study compared carbamazepine with antipsychotics as the sole treatment for schizophrenia. No differences in terms of mental state were found when comparing 50% reduction in BPRS scores (1 RCT n=38, RR 1.2 CI 0.8 to 1.9). A favourable effect for carbamazepine was found when more people who received the antipsychotic (perphenazine) had parkinsonism (1 RCT n=38, RR 0.03 CI 0.00 to 0.04, NNH 1 CI 0.9 to 1.4).
Eight studies compared adjunctive carbamazepine versus adjunctive placebo. Adding carbamazepine to antipsychotic treatment was as acceptable as adding placebo with no difference between the numbers leaving the study early from each group (8 RCTs n=182, RR 0.5 CI 0.2 to 1.4). Carbamazepine augmentation was superior compared with antipsychotics alone in terms of overall global improvement, but participant numbers were low (2RCTs n=38, RR 0.6 CI 0.4 to 0.9, NNT 2 CI 1 to 5). There were no differences for the mental state outcome of 50% reduction in BPRS scores (6 RCTs n=147, RR 0.9 CI 0.7 to 1.1). Less people in the carbamazepine augmentation group had movement disorders than those taking haloperidol alone (1 RCT n=20, RR 0.4 CI 0.1 to 1.0). No data were available for the effects of carbamazepine on subgroups of people with schizophrenia and aggressive behaviour, negative symptoms or EEG abnormalities or with schizoaffective disorder.

Authors' conclusions

Based on currently available randomised trial-derived evidence, carbamazepine cannot be recommended for routine clinical use for treatment or augmentation of antipsychotic treatment of schizophrenia. At present large, simple well-designed and reported trials are justified especially if focusing on those with violent episodes and people with schizoaffective disorders or those with both schizophrenia and EEG abnormalities.

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