[Clozapine and refractory schizophrenia. Long-term prospective study of 20 patients]

Clozapine, a dibenzodiazepine derivative, has potent antipsychotic activity. But bone marrow suppression resulting in agranulocytosis has been associated with clozapine treatment; thus its clinical development has been delayed and the administration of this drug has been restricted to treatment-resistant schizophrenic patient. This report describes an open prospective study of the effects of clozapine on symptomatology of patients who are refractory to neuroleptics. Authors prospectively followed up until 36 months, 20 DSM III-R schizophrenic patients who had failed to respond to various neuroleptics (7.7 +/- 3.0). When clozapine treatment was initiated, the mean duration of the illness was 17 +/- 10 years. Various scales were used for evaluation: total BPRS, BPRS "positive symptoms", BPRS "negative symptoms", PANSS positive and PANSS negative were realized at days 0 and 15, months 1, 2 and 3 and then every 3 months. Significative improvements in total BPRS, BPRS positive symptoms and PANSS positive were noted at day 15 (p < 0.005, p < 0.026, p < 0.02, respectively); clozapine produced significant improvement on the BPRS negative symptoms and the PANSS negative at 1 month (p < 0.03 and p < 0.008, respectively). Side effects were studied: dry mouth was more prominent in the first month after wash-out (15%), while salivation was more and more prevalent (20% within the first month; 53% beyond). There was no agranulocytosis in this cohort; 2 cases (10%) of eosinophilia occurred during the first month; 20% of the patients experienced an increase in total white blood cell count (> 12.000/mm3). Weight gain (> 5 kg) affected 32% of patients.(ABSTRACT TRUNCATED AT 250 WORDS)