Clozapine as treatment of first choice in first psychotic episodes. What do we know?

Schizophrenia is currently conceptualized as a neurodevelopmental disorder with progressive clinical, neurophysiological and neurostructural deterioration mostly occurring at early stages of the disease. During the last years, several early intervention programs have tried to modify the natural history of the disease. The choice of antipsychotic treatment adapted to the specific needs of the patient would make it possible to optimize the results of the intervention programs in first psychotic episodes. Clozapine has become a keystone in the treatment of psychosis, with multiple contributions to the treatment of schizophrenia. Clozapine has been proven superior to other antipsychotics in efficacy and effectiveness with comparable cost-effectiveness to that accepted for many medical interventions. On the other hand, recent studies indicate that the incidence and mortality of clozapine-induced agranulocytosis could be lower than previously estimated and that all-cause mortality due to clozapine is less than that associated to other antipsychotic drugs. However, inspite of clinical guideline recommendations, clozapine is used less and later than recommended. There is a lack of studies comparing clozapine with other antipsychotics in first episode psychosis patients. The aim of our paper is to review the current medical evidence about the use of clozapine as a first-line treatment for naive first episode psychosis patients.