Melperone in the treatment of neuroleptic-resistant schizophrenia

Melperone is an effective antipsychotic drug that has been reported to have atypical properties, i.e. low extrapyramidal side effect liability at clinically effective doses. It also does not increase serum prolactin levels. Its effectiveness for patients with neuroleptic (treatment)-resistant schizophrenia has not been evaluated. In this study, melperone was administered, in an open trial design of 6 weeks' duration, to 44 patients with chronic neuroleptic-resistant schizophrenia. The Global Assessment Scale (GAS), Brief Psychiatric Rating Scale (BPRS) and measures of extrapyramidal symptoms and other clinical variables were assessed at baseline and 6 weeks. Thirty-seven patients completed the 6-week trial. Melperone significantly improved overall psychiatric status as measured by GAS score for all evaluable subjects [last value carried forward (LVCF) and a completers analysis]. No significant effects on BPRS measures of psychopathology scores were found in the LVCF or completers analysis. Patients who showed ≥ 20% decrease in the BPRS Total score (N = 7) were more likely to have high baseline psychopathology, as measured by BPRS Total and Anxiety-Depression subscales, than those who showed ≥ 20% increase in the BPRS Total score (N = 8). Non-responders to melperone generally did not respond to subsequent treatment with clozapine, indicating that this group of patients was very treatment resistant. Melperone was not associated with worsening of extrapyramidal symptoms, elevation in plasma prolactin levels, or an increase in body mass index (BMI). The results suggest that a proportion of neuroleptic-resistant patients with schizophrenia respond to melperone, which requires further controlled study.