[Atypical antipsychotics in first-episode psychosis: a review]

The management of patients with first-episode psychosis (FEP) is a difficult, but challenging task. Early and efficient treatment may influence long-term clinical outcome. Atypical antipsychotics (A-AP) are commonly prescribed in this population, but few data exist to establish their appropriate usage in the management of FEP. Our purpose is to review the literature and to summarize current data on the prescription of A-AP in FEP.

Studies assessing efficacy or safety of A-AP in FEP were identified by searches in Medline (up to April 2006). The following nine drugs were considered for this review: clozapine, olanzapine, risperidone, amisulpride, aripiprazole, quetiapine, ziprasidone, zotepine, and sertindole.

Only four A-AP (clozapine, quetiapine, olanzapine, and risperidone) were evaluated as treatment of FEP. All of them show the same efficacy as conventional antipsychotics (C-AP). Clozapine has no benefit over C-AP in the treatment of naive patients. It entails a high rate of treatment discontinuation because of the need for regular white blood cell monitoring explained by the risk of agranulocytosis. Hence, clozapine may not be a first-line treatment of FEP. Tolerance to quetiapine and olanzapine is better than C-AP regarding extrapyramidal side effects, but weight gain induced by these two A-AP may be very disabling in a young population. Considering results from head-to-head comparative studies, olanzapine may be more effective than risperidone when an affective component is associated with the FEP symptomatology, but more data are needed to demonstrate this point. Risperidone is a relatively well-tolerated compound when it is prescribed at doses lower than 4 mg/d. It is the only A-AP that showed greater efficacy than C-AP to prevent relapse in patients with FEP. Unfortunately, information regarding the preventive efficacy of the other A-AP are lacking.

Further studies, particularly longer-term studies, are needed to explore the impact of A-AP prescription in FEP on the course of psychotic disorders. The common use of A-AP as treatment of FEP is justified by a relatively better tolerance compared to C-AP, and by the hypothesis-not demonstrated-of a better effect on long-term outcome.