A 6-week, randomized, multicentre, open-label study comparing efficacy and tolerability of amisulpride at a starting dose of 400 mg/day versus 800 mg/day in patients with acute exacerbations of schizophrenia.

BACKGROUND: It has been suggested that neither dose titration nor the use of a loading dose was required for amisulpride and that 800 mg/day could be given from the first day with a low risk of extrapyramidal symptoms (EPS). However, no direct study of the need for dose titration has been conducted.

OBJECTIVE: This study aimed to compare the efficacy, tolerability and subjective experience of amisulpride between a group receiving an initial dose of 800 mg/day (AMI-800 group) and a group titrating up from an initial dose of 400 mg/day (AMI-400 group) over a period of 6 weeks.

METHODS: A total of 68 patients with acute exacerbations of schizophrenia participated in this 6-week randomized, multicentre, open-label study of amisulpride. Thirty patients were randomly assigned to the group that received an initial dose of 400 mg/day, which was then titrated up during the first 4 weeks following a fixed schedule. Thirty-eight patients were randomly assigned to the group receiving an initial dose of amisulpride 800 mg/day, which they took until the end of the fourth week. During the fifth and sixth weeks, the doses were adjusted flexibly in both groups. Our primary outcome measures were the Clinical Global Impression (CGI) scale and the changes over time in the total and subscale scores of the Positive and Negative Syndrome Scale (PANSS).

RESULTS: We found no significant between-group differences in clinical improvement on the CGI and the PANSS. However, when responders were defined as those patients who experienced at least a 30 % reduction in the PANSS total scores obtained at baseline, a higher proportion of those in the AMI-800 group met the criterion for responsiveness from week 4 (week 4: 68.4 % vs 40.0 %, p = 0.02; week 6: 71.1 % vs 43.3 %, p = 0.02). Irrespective of treatment group, significant proportions of patients developed hyperprolactinaemia (86 %) and EPS (35 %). However, no statistically significant differences in the overall incidence of adverse events were observed between the two treatment groups. There were also no group differences in subjective quality of life and attitudes toward antipsychotic medication.

CONCLUSION: These results suggest that it may be useful to begin therapy, especially for acute exacerbations of schizophrenia, with an initial dose of amisulpride 800 mg/day to obtain maximal efficacy without any significant side effects.