Clozapine Combined with Different Antipsychotic Drugs for Treatment-Resistant Schizophrenia

Summary

A Cochrane review [Abstract] 1 included 5 studies with a total of 309 subjects. The follow-up time was from 8 to 52 weeks. There was no data for service utilisation and quality of life.

• Clozapine plus aripiprazole vs. clozapine plus haloperidol (1 RCT, n=105):There was no long-term significant difference between aripiprazole and haloperidol combinations in change of mental state (MD 0.90, 95% CI -4.38 to 6.18). There was a benefit of aripiprazole for adverse effects measured by the Liverpool University Neuroleptic Side Effect Rating Scale (LUNSERS) at 12 weeks (MD -4.90, 95% CI -8.48 to -1.32) and 24 weeks (MD -4.90, 95% CI -8.25 to -1.55), but not 52 weeks (MD -4.80, 95% CI -9.79 to 0.19). Similar numbers of participants from each group left the study early (RR 1.27, 95% CI 0.72 to 2.22).
• Clozapine plus amisulpride vs. clozapine plus quetiapine (1 RCT, n=50): There was a significant benefit of amisulpride over quetiapine in the short term, for both change in global state (Clinical Global Impression (CGI): MD -0.90, 95% CI -1.38 to -0.42) and mental state (Brief Psychiatric Rating Scale (BPRS): MD -4.00, 95% CI -5.86 to -2.14). Similar numbers of participants from each group left the study early (RR 0.20, 95% CI 0.02 to 1.60)
• Clozapine plus risperidone vs. clozapine plus sulpiride (1 RCT, n = 60):There was no difference between risperidone and sulpiride for clinically significant response, defined by the study as 20% to 50% reduction in Positive and Negative Syndrome Scale (PANSS) (RR 0.82, 95% CI 0.40 to 1.68). There were similar equivocal results for weight gain (RR 0.40, 95% CI 0.08 to 1.90) and mental state (PANSS total: MD -2.28, 95% CI -7.41 to 2.85). No-one left the study early.
• Clozapine plus risperidone vs. clozapine plus ziprasidone (1 RCT):There was no difference between risperidone and ziprasidone for clinically significant response (RR 0.80, 95% CI 0.28 to 2.27; n = 24), change in global state CGI-II score (MD -0.30, 95% CI -0.82 to 0.22; n = 22), change in PANSS total score (MD 1.00, 95% CI -7.91 to 9.91; n = 16) or leaving the study early (RR 1.60, 95% CI 0.73 to 3.49; n = 24).
• Clozapine plus ziprasidone vs. clozapine plus quetiapine (1 RCT, n = 63):There was, in the medium term, a superior effect for ziprasidone combination compared with quetiapine combination for clinically significant response in mental state (> 50% reduction PANSS: RR 0.54, 95% CI 0.35 to 0.81), global state (CGI - Severity score: MD -0.70, 95% CI -1.18 to -0.22) and mental state (PANSS total score: MD -12.30, 95% CI -22.43 to -2.17). There was no effect for leaving the study early (RR 0.52, CI 0.05 to 5.41).