Clozapine does not constitute a first-line treatment due to the occurrence of
agranulocytosis. However, the benefit/risk ratio fully justifies its use in two situations: résistance to
neuroleptics; intolerance to
neuroleptics. There are no internationally recognized objective criteria to devine resistance. The ones defined in the well-restricted methodological environment of a clinical trial are generally not applicable to daily practice. In particular, the accepted criteria do not always take into account the personal factors, the social and environmental context and rehabilitation programs. May et al. for example defined in 1988 the degree of response to
therapy based on clinical improvement as well as social integration. It As was widely recognized that if the severity of residual symptoms (grade 5 response) requires the hospitalization, treatment with
clozapine is warranted. For partial responders to classical treatment (grade 4 response) who could benefit from
clozapine, the risk ratio of
clozapine needs to be further evaluated. The identification of predictive factors of response to
therapy would allow a nosel approach of this indication. According to certain authors, paranoid type responds best to
therapy. However, the evidence collected to date needs to be confirmed. In particular, the effects of
clozapine on predominantly negative symptoms require further investigations. In contrast to several european studies, intolerance to
neuroleptics is rarely a reason for initiation of
clozapine therapy. This would indicate that the appreciation of intolerance to
neuroleptics notably varies from one country to the next. Intolerance criteria to be further specified as well as the benefit/risk ratio.