Amisulpride augmentation in patients with schizophrenia partially responsive or unresponsive to clozapine. A randomized, double-blind, placebo-controlled trial

Introduction: Only limited data are available on the effectiveness of augmented antipsychotics to clozapine therapy in chronic schizophrenia. We conducted a randomized, double-blind, placebo-controlled pilot study to evaluate the efficacy and safety of augmentation with the atypical neuroleptic amisulpride to clozapine in a small sample group of patients. Methods: 16 patients with the DSM-IV diagnosis of chronic schizophrenia and partially responsive to clozapine participated in this pilot study. Patients on a steady dose of clozapine randomly received either clozapine and amisulpride 400 mg/day (n=7) or clozapine and amisulpride 600 mg/day (n=6) or clozapine and placebo for 6 weeks (n=3). Efficacy measures were BPRS, CGI, GAF and MADRS score. Side effects and prolactin levels were obtained. Primary outcome measure were BPRS score changes. Results: The beneficial effect of augmented amisulpride at a daily dose of 600 mg was observed in the mean scores of secondary outcome measures, as assessed by GAF, CGI and MADRS. Measures of primary objectives failed to improve significantly. No reduction in BPRS total score was achieved due to lack of power of the study, whereas the BPRS subscore activity had a tendency to improve. Amisulpride was more beneficial in a higher than a lower dose. No severe side-effects occurred, but tremor, bradykinesia, akathisia and elevated prolactin levels were recorded. Discussion: Augmented amisulpride improved the global outcome of patients suffering from chronic schizophrenia in this pilot study and tended to be a helpful treatment option in cases of partial or non-responsiveness to clozapine. Limitations emerge from the small sample size and lack of power. Further investigation requires a larger number of patients to be included.