L’étude présentée avait pour objectif de recueillir des données sur les modalités de prescription de la clozapine en Île-de-France, dix ans après sa réintroduction. Il s’agit d’une étude rétrospective sur une population constituée de 57 hommes et 41 femmes, d’un âge moyen de 38 ans, présentant des formes cliniques de schizophrénie variées, avec une durée moyenne du traitement neuroleptique sur la vie entière de 10,3 ans. La symptomatologie prévalente au cours de l’évolution était le plus souvent des hallucinations auditives (41 %). La principale indication de la clozapine était les schizophrénies résistantes (88,5 %) et la durée moyenne du traitement était de 2 ans et 4 mois. L’efficacité de la clozapine était évaluée comme bonne ou moyenne chez 77,9 % des patients, à des posologies moyennes de 322 mg par jour, et sa tolérance était jugée satisfaisante par la moitié des cliniciens ; 21,6 % des patients avaient arrêté la clozapine et 2/3 des sujets avaient un traitement psychotrope associé à la clozapine (benzodiazépines : 18,4 %, antidépresseurs : 15,3 %). L’efficacité de la clozapine était étudiée en fonction de différentes variables, sans différence significative de l’efficacité en fonction du sexe, des types de schizophrénie, de la symptomatologie prévalente au cours de l’évolution ou de la consommation de toxiques. De même, il était recherché si certains facteurs pouvaient influencer la survenue d’une granulopénie sans que des résultats significatifs au plan statistique ne ressortent. Cette étude témoigne de l’intérêt clinique de la clozapine dans toutes les formes de schizophrénie ; elle incite à son usage plus précoce dans l’évolution de la maladie, en respectant plus rigoureusement les restrictions en matière de coprescription avec d’autres psychotropes.

Introduction. Clozapine, synthesized in the sixties, is an atypical antipsychotic drug whose history has been marked by its haematological toxicity. The purpose of this study was, ten years after it had been replaced at French psychiatrists" disposal, to gather data on the prescription modalities of clozapine, assess whether some factors could affect its efficacy, and describe the population of schizophrenic patients concerned. Methodology. Psychiatrists in the Paris region were asked to answer a questionnaire about their patients treated with clozapine. The information collected was about socio-demographic data, history of psychiatric disorder and the way clozapine was used. It was a retrospective study concerning 98 patients. Results. Subjects were 57 men and 41 women, with a mean age of 38 years. The majority of patients came from metropolitan France. Patients suffered from various clinical subtypes of schizophrenia, as assessed according to DSM IV criteria. Predominant symptomatology during lifetime was most often auditory hallucinations (41 %). Mean duration of lifetime neuroleptic treatment was 10.3 years and breaks in follow-up were rare. Mean number of hospitalisations was 6.9 and a little less than half of the patients had been committed involuntarily. Lastly, 38 % of patients had attempted suicide at least once and 35 % had expressed hetero-agressive behavior. Main indication of clozapine was resistant schizophrenia (88.5 % of patients) and mean duration of treatment was 2 years and 4 months. Treatment efficacy was assessed as good or medium in 77.9 % of patients, at mean doses (322 mg per day) in keeping with data from the literature. Tolerance was considered on the whole as satisfactory by half of the clinicians. Among the 98 patients of the study, 21.6 % had stopped taking clozapine. The reasons for withdrawal were : inefficacy (6.2 %), granulopenia (5.2 %), epilepsy (1 %) and 8.2 % for various reasons (half of these cases being non-compliance with treatment). The study of the 5 cases of granulopenia showed that 3 patients had another associated psychotropic medication : 1 patient received only clozapine as monotherapy, 1 data was missing. Two thirds of all patients were receiving another psychotropic drug in association with clozapine, mainly benzodiazepines (18.4 %), antidepressants (15.3 %) or mood stabilizers (7.1 %). The « therapeutic efficacy » variable was compared with some variables in order to isolate factors possibly associated with a better efficacy of clozapine or, on the contrary, with a population of patients poorly responding to treatment. However, no statistically significant difference appeared according to the variables studied, such as gender or lifetime duration of neuroleptic treatment. Moreover, there was no statistically significant difference in efficacy according to schizophrenia subtype, main symptomatology during the course of illness or substance abuse. We studied whether any factor could affect the occurrence of granulopenia. No statistically significant difference was found. The mean age of patients having stopped the treatment because of granulopenia was higher than in the group with other reasons for interruption, but did not reach statistical significance. A trend also appeared towards female predominance (60 % of women in the granulopenia group) and 3/4 of patients who had stopped their treatment because of agranulocytosis received another psychotropic drug in association with clozapine. Conclusion. As expected, the main indication for prescribing clozapine was resistant schizophrenia, but contrary to data from the international literature, the efficacy profile was the same whatever the clinical subtype of schizophrenia. The tolerance to clozapine was considered on the whole as satisfactory, but the high proportion of granulopenias leading to treatment withdrawal (5.2 % of patients) confirms the need to remain cautious and stresses the importance of regular haematological monitoring. Furthermore, the study of the prescription modalities of clozapine shows that contrary to the guidelines, clozapine is often associated with other psychotropic drugs. In this study, it is striking to note that 75 % of granulopenias occured in a coprescription situation.