Amisulpride compared with standard neuroleptics in acute exacerbations of schizophrenia: three efficacy studies

Abstract

Three double-blind studies that included acutely ill schizophrenic patients were undertaken to assess the efficacy of amisulpride, an atypical antipsychotic with a selective affinity for dopamine D2, and D3, receptors. In the first study fixed doses of amisulpride (400, 800 and 1200 mg/day) and 16 mg/day of haloperidol were compared with 100 mg/day of amisulpride for a 4-week period. Efficacy was assessed using the Brief Psychiatric Rating Scale (BPRS), subscales of the Positive and Negative Symptom Scales (PANSS) and the Clinical Global Evaluation (CGI). Data were obtained on 319 subjects with the revised third-edition Diagnostic and Statistical Manual of Mental Disorders (DSM-III-R) criteria for schizophrenia. The highest improvement, in terms of BPRS total scores, occurred in the two groups taking 400 mg or 800 mg amisulpride. These doses also induced less extrapyramidal disturbance compared with haloperidol. The second study compared amisulpride with haloperidol: 95 patients were treated for 6 weeks with 800 mg/day of amisulpride and 96 patients with 20 mg/day of haloperidol. Efficacy criteria were the same as in the first study. Amisulpride at 800 mg/day was at least as efficacious as 20 mg haloperidol for the positive symptoms of schizophrenia, but was significantly more effective against negative symptoms (PANSS negative subscale, P = 0.038). There was also a significantly lower incidence of parkisonism in the amisulpride group. The third study compared amisulpride with flupenthixol: 70 patients were treated with 1000 mg/day of amisulpride and 62 patients with 25 mg/day of flupenthixol for a 6-week period. The mean improvement in the BPRS total score was greater in the amisulpride group, although this difference just failed to reach statistical significance (P = 0.059). Both drugs improved negative symptoms (Scale for the Assessment of Negative Symptoms), but the effect was more marked with amisulpride. Differences were statistically different in favour of amisulpride for positive symptoms. These studies show that amisulpride has optimal efficacy at doses of between 400 and 800 mg/day. It was at least as effective as reference drugs in the treatment of positive symptoms, and also reduced negative symptoms. Furthermore, amisulpride provoked fewer extrapyramidal side effects than standard reference drugs.