Dosage finding and outcome in the treatment of schizophrenic inpatients with amisulpride. Results of a drug utilization observation study.

OBJECTIVES: Amisulpride is an unique neuroleptic drug insofar as it has a dual pharmacodynamic effect. At low doses it blocks selectively presynaptic autoreceptors, and at high doses it blocks postsynaptic D(2)/D(3) receptors. This allows the dosage to be adjusted and the treatment tailored to various clinical situations. It is unknown whether this pharmacological property has any bearing for routine treatment. The questions are: which dosages of amisulpride are chosen by physicians in the treatment of schizophrenic inpatients and does this dosage handling deviate from prescription guidelines?; which factors can explain dosage selection, and what is the treatment outcome with different dosages? The study pertains to drug management and dosage finding as principal factors in explaining positive and negative medication results.
METHODS: In a drug utilization observation study the prescribing of amisulpride for 811 schizophrenic inpatients from 240 psychiatric hospitals was monitored for 8 weeks. Standardized assessment included dosage, the positive and negative symptom scale (PANSS), the clinical global impression rating (CGI), the patients' subjective reaction to amisulpride, psychosocial functioning, EPS and other adverse events. The mean observation period was 49 days.
RESULTS: The mean initial daily dose of amisulpride was 361 mg/day. The mean daily dose at day 56 was on average 550 (SD 266) mg/d, ranging from 100 mg to 1600 mg. 17.9% of patients received a maximum dose up to 399 mg/d, 48.1% between 400 and 799 mg/d, and 25.5% 800 mg/d and higher. Higher doses were preferably prescribed for males, patients with involuntary admission, patients with paranoid schizophrenia with acute exacerbation, high CGI and high PANSS-positive scores. Patients with higher doses of amisulpride at the same time received higher rates of additional other neuroleptic drugs. Higher doses yield better results in very severe cases.
CONCLUSIONS: Prescribed dosages were in the lower range of what is recommended for acute cases. Dosage was significantly influenced by the severity of the illness. Polypharmacy was the rule rather than the exception. Efficacy rates under conditions of routine care were similar to the results from controlled clinical trials, which speaks for their generalizability. Very severe cases profit from higher doses. Copyright 2004 John Wiley & Sons, Ltd.