Effects of amperozide in schizophrenia. An open study of a potent 5-HT2 receptor antagonist

Ten male inpatients (aged 29 +/- 6 years) with a DSM-III diagnosis of schizophrenia participated in a 4-week open dose escalation study of amperozide, a novel 5-HT2 receptor antagonist. The maximum daily dose of amperozide was 20 mg. A close dose-plasma concentration relationship showed considerable interindividual variation in the steady-state plasma levels at a given dose. Approximately equal concentrations of amperozide and its metabolite, N-deethylated amperozide, were seen in plasma. The prolactin levels were not increased during amperozide treatment. No changes occurred in hematological or other laboratory parameters. ECG showed changes in T-wave morphology and a prolongation of the QTc time. One patient was withdrawn from the trial due to aggravation of psychotic symptoms, and two patients had a brief, temporary discontinuation of the drug due to somatic illness. Six patients were improved during amperozide treatment, as assessed by the Clinical Global Improvement Scale. Among the responders the total CPRS was reduced by a mean of 64% and total BPRS score by a mean of 46%. Mild tremor was a frequent side effect, but other extrapyramidal symptoms were rare. Nausea was seen in six patients and of a more pronounced character in one patient. In general, the severity of the side effects increased with increasing doses of amperozide.