Antipsychotic effects of bretazenil, a partial benzodiazepine agonist in acute schizophrenia--a study group report

The results of an open tolerability and exploratory efficacy study of bretazenil, a partial benzodiazepine-receptor agonist in hospitalized schizophrenic patients with an acute psychotic episode (DSM-III-R criteria), are presented. The duration of the study was 6 weeks, with a mandatory titration (ascending doses of 3-18 mg/day) period of 14 days. The assessment criteria for tolerability were the frequency of adverse events (including EPS), vital signs and laboratory tests. The efficacy criteria, which were only descriptively analysed, were: (a) Clinical Global Impression (CGI, percentage of "very much" and "much" improvement); and (b) change in BPRS total score (e.g. percentage of patients showing > or = 40% decrease of BPRS score at the end of the treatment). Sixty-six patients (aged 21-62 years) with acute episodes of schizophrenia of moderate to marked severity (mean BPRS score = 46.3, range 26-76) were included in the study. Of these 66 patients (68%) were reportedly non-responders (n = 10) or partial responders (n = 35) to previous neuroleptic therapy. Twenty patients (30%) terminated the trial prematurely due to therapeutic failure (no improvement or worsening after 2 weeks of treatment), 17% of patients dropped out due to other reasons (transfer to other hospitals, withdrawal of consent, intercurrent diseases) and 4.5% of patients stopped the treatment due to adverse reactions. Four patients (6%) showed early complete remission and refused to be further treated. The analysis of efficacy (intention-to-treat) revealed a sustained decrease of BPRS scores with 49% of patients showing > or = 40% BPRS score change by the end of the treatment. Forty-four per cent of patients improved "very much" or "much". Eleven patients (17%) were full responders (BPRS score decrease 75-100%) and 21 patients (32%) showed at least 40% reduction of BPRS score. The reduction of BPRS scores in completers only was 60%. All BPRS factor scores decreased in parallel and, particularly, no preferential decrease of anxiety/depression subscores was found. The analysis of tolerability showed that 59% of patients presented no complaints at all. The most frequent treatment-related adverse reactions in the remaining patients were: sedation (n = 14), dizziness (n = 4) and headache (n = 3). The results of this study suggest moderate antipsychotic efficacy of bretazenil in schizophrenic patients. They encourage further investigations of partial benzodiazepine-receptor agonists in this indication, particularly because of the excellent tolerability and lack of extrapyramidal side-effects.