Zotepine versus other atypical antipsychotic drugs for schizophrenia

This review compares the effects of zotepine to other second generation antipsychotic drugs. Three trials suggest that the efficacy of zotepine may be comparable to risperidone and remoxipride. The evidence base is insufficient to provide firm conclusions as to whether zotepine is as effective or less effective than clozapine. The movement disorders and the cognitive changes appear to be similar to clozapine, risperidone and remoxipride. The need for antiparkinson medication is similar to risperidone and remoxipride, but may be associated with increased need than necessary with clozapine.

Authors' conclusions: 

The evidence base around zotepine is insufficient to provide firm conclusions on its absolute or relative effects. This is despite it being in use in Austria, France, Germany, Japan and the UK.

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In many parts of the world, particularly in industrialised countries, second generation (atypical) antipsychotic drugs have become first line treatment for people suffering from schizophrenia. The question as to whether the effects of various second generation antipsychotic drugs differ is a matter of debate.


To evaluate the effects of zotepine compared with other second generation antipsychotic drugs for people suffering from schizophrenia and schizophrenia-like psychoses.

Search strategy: 

We searched the Cochrane Schizophrenia Group Trials Register (November 2009), inspected references of all identified studies for further trials and contacted authors of trials for additional information.

Selection criteria: 

We included only randomised clinical controlled trials that compared zotepine with any forms of amisulpride, aripiprazole, clozapine, olanzapine, risperidone, sertindole or ziprasidone in people suffering from only schizophrenia or schizophrenia-like psychoses.

Data collection and analysis: 

SS and KK extracted data independently. For dichotomous data we calculated relative risks (RR) and their 95% confidence intervals (CI) on an intention-to-treat basis based on a random-effects model. For continuous data, we calculated weighted mean differences (MD) again based on a random-effects model.

Main results: 

We included three studies (total n=289; 2 RCTs zotepine vs clozapine; 1 RCT zotepine vs clozapine vs risperidone (at 4 mg, 8 mg doses) vs remoxipride. All studies were of limited methodological quality. When zotepine was compared with clozapine, it was clozapine that was found to be more effective in terms of global state (n=59, 1 RCT, RR No clinically significant response 8.23 CI 1.14 to 59.17). Mental state scores also favoured clozapine (n=59, 1 RCT, MD average score (BPRS total, high = poor) 6.00 CI 2.17 to 9.83) and there was less use of antiparkinson medication in the clozapine group (n=116, 2 RCTs, RR 20.96 CI 2.89 to 151.90). In the comparison of zotepine and risperidone, mental state scoring found no significant difference between the groups (vs 4 mg: n=40, 1 RCT, MD average endpoint score (BPRS total, high=poor) 1.40 CI -9.82 to 12.62; vs 8 mg: n=40, 1 RCT, MD -1.30 CI -12.95 to 10.35) and use of antiparkinson medication was equivocal (vs 4 mg: n=40, 1 RCT, MD 1.80 CI -0.64 to 4.24; vs 8 mg: n=40, 1 RCT, MD 2.50 CI -0.05 to 5.05). Finally, when zotepine was compared with remoxipride, again no effect was found for mental state (n=58, 1 RCT, MD average endpoint score (BPRS total, high=poor) 5.70 CI -4.13 to 15.53) and there was no significant difference between the two groups in terms of use of antiparkinson medication (n=49, 1 RCT, RR 0.97 CI 0.41 to 2.29).

Data on important other outcomes such as other adverse events, service use or satisfaction with care, quality of life were not available.