Zotepine for schizophrenia.
BACKGROUND
Typical antipsychotic drugs are widely used as first line treatment for people with schizophrenia. The atypical class of antipsychotic drugs, however, is making important inroads into this approach and zotepine is one such compound. It is a dopamine antagonist and claimed to be to be particularly effective for negative symptoms


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


METHODS
Electronic searches of Biological Abstracts (1980-1999), CINAHL (1982-1999), The Cochrane Library (Issue 1, 1999), The Cochrane Schizophrenia Group's Register (January 1999), EMBASE (1980-1999), Dialog Corporation Datastar service (1999), MEDLINE (1966-1999), and PsycLIT (1974-1999) were undertaken. References of all identified studies were searched for further trials. Knoll Pharmaceuticals and authors of trials were contacted.


METHODS
All randomised clinical trials that compared zotepine to other treatments for people with schizophrenia or other psychoses were included.


METHODS
Citations and, where possible, abstracts were independently inspected by reviewers, papers ordered, re-inspected and quality assessed. Data were independently extracted. Data were excluded if loss to follow up was greater than 50%. For homogeneous dichotomous data the relative risk (RR), 95% confidence interval (CI) and, where appropriate, the number needed to treat (NNT) and numbers needed to harm (NNH), were calculated on an intention-to-treat basis. For continuous data, weighted mean differences were calculated (WMD). All data were inspected for heterogeneity.


RESULTS
All outcomes were short term (4-12 weeks). Limited data suggest that zotepine is an antipsychotic, at least as effective as typical drugs. Mental state measures of 'no clinically important improvement' favour zotepine when compared to other active drugs (n=356, RR 0.8 CI 0.7-0.9, NNT 7 CI 4-22). About one third of people in both 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.


CONCLUSIONS
Zotepine may be a valuable addition to the increasing ranks of atypical antipsychotic drugs. More data from already existing studies is urgently needed to increase the confidence in the findings of this review. New data from well planned, conducted and reported long term pragmatic randomised trials are necessary. Otherwise clinical use of zotepine will be based on speculation on the meaning of the findings of short explanatory trials for everyday practice.
Fenton
M
M
Trent Ward, South Tees Community and Mental Health Services Trust, St Lukes Hospital, Marton Road, Middlesborough, Cleveland, UK, TS4 3EE. rsmor@globalnet.co.uk
Morris
S
S
De-Silva
P
P
Bagnall
A
A
Cooper
S J
SJ
Gammelin
G
G
Leitner
M
M
D014150:Antipsychotic Agents / Q000627:therapeutic use*; D003988:Dibenzothiepins / Q000627:therapeutic use*; D006801:Humans; D011618:Psychotic Disorders / Q000188:drug therapy / Q000523:psychology; D012559:Schizophrenia / Q000188:drug therapy*
D014150:Antipsychotic Agents; D003988:Dibenzothiepins; C022172:zotepine