A Cochrane review included 3 studies with a total of 289 subjects with schizophrenia. Two RCTs compared zotepine vs clozapine; 1 RCT compared zotepine vs clozapine vs risperidone (at 4 mg, 8 mg doses) vs remoxipride. The follow-up time in trials was from 4 to 12 weeks. Data on other adverse events, service use, satisfaction with care or quality of life were not available.
• Zotepine vs. clozapine: Clozapine was found to be more effective in terms of global state (RR 8.23, CI 1.14 to 59.17; 1 RCT, n=59). Mental state scores also favoured clozapine (MD average score (Brief Psychiatry Rating Scale (BPRS) score total, high = poor) 6.00, CI 2.17 to 9.83; 1 RCT, n=59) and there was less use of antiparkinson medication in the clozapine group (RR 20.96, CI 2.89 to 151.90; 2 RCTs, n=116).
• Zotepine vs. risperidone: Mental state scoring found no significant difference between the groups (vs. 4 mg: MD average endpoint score (BPRS total, high=poor) 1.40, CI -9.82 to 12.62; 1 RCT, n=40; vs. 8 mg: MD -1.30, CI -12.95 to 10.35; 1 RCT, n=40) and use of antiparkinson medication was equivocal (vs. 4 mg: MD 1.80, CI -0.64 to 4.24; 1 RCT, n=40; vs. 8 mg: MD 2.50, CI -0.05 to 5.05; 1 RCT, n=40).
• Zotepine vs. remoxipride: No difference was found for mental state (MD average endpoint score (BPRS total, high=poor) 5.70, CI -4.13 to 15.53; 1 RCT, n=58) and there was no significant difference between the groups in terms of use of antiparkinson medication, either (RR 0.97, CI 0.41 to 2.29; 1 RCT, n=49).
Comment: The quality of the evidence is downgraded by study quality (inadequate allocation concealment, unclear blinding, short follow-up), imprecise results (limited study size for each comparison) and indirectness of evidence (differences in outcomes).