Zotepine for schizophrenia

Schizophrenia is a chronic, relapsing mental illness and has a worldwide lifetime prevalence of about 1% irrespective of culture, social class and race. Schizophrenia is characterised by positive symptoms such as hallucinations and delusions and negative symptoms such as emotional numbness and withdrawal. One quarter of those who have experienced an episode of schizophrenia recover and the illness does not recur. Another 25% experience an unremitting illness. Half of those diagnosed do have a recurrent illness but with long episodes of considerable recovery from the positive symptoms. Current medication is effective in reducing positive symptoms, but negative symptoms are fairly resistant to treatment. In addition, drug treatments are associated with adverse effects and the overall cost of the illness to the individual, their carers and the community is considerable.

Antipsychotic medications are categorised as typical antipsychotics (i.e. first generation: chlorpromazine, haloperidol, etc) and atypical antipsychotics (i.e. second generation: amisulpiride; olanzapine; risperidone etc) and both are the mainstay of treatment for people with schizophrenia. Zotepine is an atypical antipsychotic and the atypicals are thought to have a different adverse effects profile to typicals; in particular they are thought less likely to cause movement disorders.

We sought all relevant randomised controlled trials comparing zotepine with placebo and other antipsychotics but found very few. Zotepine may well be a useful drug, but currently data are sparse, and importantly this data emanates from a company with an interest in showing zotepine to be effective and safe.

Authors' conclusions: 

Zotepine may be a valuable addition to the class of atypical antipsychotic drugs. However, more data from existing studies is urgently needed to increase confidence in the findings of this review. In addition to this, new data from well planned, conducted and reported long term pragmatic randomised trials are needed. Otherwise clinical use of zotepine will be based upon speculation of short explanatory trials for everyday practice.

Read the full abstract...

Zotepine is a relatively new antipsychotic often used for the treatment of people with schizophrenia. It is claimed to be particularly effective for negative symptoms.


To determine the effects of zotepine compared with placebo, typical and other atypical antipsychotic drugs for schizophrenia and related psychoses.

Search strategy: 

For the 2006 update we searched the Cochrane Schizophrenia Group's register of trials.

Selection criteria: 

We included all randomised clinical trials comparing zotepine with other treatments for people with schizophrenia or other psychoses.

Data collection and analysis: 

We independently inspected citations and abstracts, ordered papers, re-inspected these and assessed their quality. For homogenous dichotomous data we calculated the relative risk (RR), 95% confidence intervals (CI) and, where appropriate, numbers needed to treat/harm (NNT/H) on an intention-to-treat basis. For continuous data, we calculated weighted mean differences (WMD). We inspected all data for heterogeneity.

Main results: 

The review currently includes 11 studies with 966 participants. Most outcomes were short term (4-12 weeks). We found no data for outcomes such as relapse, time in hospital, satisfaction with care and day-to-day functioning. Compared with placebo, mental state ratings favoured zotepine (n=106, 1 RCT, RR No 20% decrease in BPRS 0.44 CI 0.3 to 0.7, NNT 3 CI 2 to 6) using the last observation carried forward method. For the comparison with typical drugs, limited data suggest that zotepine may be as effective as these older medications. Mental state measures of 'no clinically important improvement' favour zotepine when compared with other active drugs (n=356, 4 RCTs, RR 0.77 CI 0.7 to 0.9, NNT 7 CI 4 to 22). About one third of people in both the zotepine and control groups left the studies before trial completion. Zotepine may result in less movement disorder adverse effects than typical antipsychotic drugs. Trials have not highlighted clear differences between zotepine and other atypical drugs.