Carbamazepine for schizophrenia

Leucht S, Kissling W, McGrath J, White P

Published Online:

August 8, 2010

Schizophrenia is a serious mental illness which can cause people to change the way they sense and understand the world. It can be very serious and continue to affect some people throughout their life. Although most people with this illness can be helped by taking antipsychotic medication, 5-15% will continue to suffer from debilitating symptoms. For this group of people a variety of medical options are available to reduce these symptoms, including adjusting the dose of medication, changing to another antipsychotic, or using drugs other than antipsychotics.

Carbamazepine is a drug which has been used to treat epilepsy since the 1950s. It is also used as a mood stabiliser when people alternate between very ‘high’ and depressed moods (bi-polar affective disorder). This review looks at the effectiveness of carbamazepine when compared to no active medication (placebo), an antipsychotic, or when it is used in addition to an antipsychotic in clinical trials on people who have schizophrenia both with additional mood problems (schizoaffective disorder), and without.

Ten trials were found which included a total of 258 people. All except one of these studies were carried out in a hospital setting. One small trial compared carbamazepine treatment with placebo (31 people) and found that there was no significant difference between these in respect to preventing relapse, mental state or development of adverse effects. Another single study of 38 people compared carbamazepine (as a single treatment) with the antipsychotic perphenazine (as a single treatment) and found no significant difference between the people in the two groups except that those on perphenazine were more likely to have movement side effects and be taking medication for them.

The remainder of the trials compared antipsychotic plus carbamazepine with antipsychotic plus placebo. Two of these trials (38 people) showed that when carbamazepine was taken with an antipsychotic, there was a general improvement in over half of these people. However, for the majority of the outcomes for which there was acceptable data, there was no significant difference between the two groups. Since all of these trials were small, there is not enough data to clarify whether carbamazepine reduces symptoms without giving too many adverse effects in people with schizophrenia and schizoaffective disorders who are resistant to treatment with antipsychotics alone. A larger well designed trial may provide more robust evidence to support the treatment options for these people.

(Plain language summary prepared for this review by Janey Antoniou of RETHINK, UK www.rethink.org).

Abstract (click to read)

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.

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

Assessed as up to date:

May 21, 2007

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Primary Review Group:

Schizophrenia Group

Health topics:

Mental health > Schizophrenia & psychosis > Other drug treatments

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