Optimizing outcome with antipsychotic treatment in first-episode schizophrenia: Balancing efficacy and side effects

The initial tailoring of antipsychotic medication for an individual experiencing a first episode of psychosis (FEP) is a critical empirical process with potentially far-reaching consequences. This article reviews the results of randomized treatment trials of clinically available first-generation antipsychotics (FGAs) and second-generation antipsychotics (SGAs) in individuals experiencing FEP, addressing these medications' relative therapeutic potentials and their proclivities to produce a range of unwanted side effects. The authors will argue that the best clinical long-term outcomes will be achieved with: 1) a "succeed-first" strategy of identifying those treatment-responsive individuals who will have a good response to neuroleptic threshold doses of well-tolerated FGAs (thereby avoiding weight gain, insulin resis tance, and prolactin-induced changes in gender-specific physiology); and, 2) an early trial of clozapine in treatment-nonresponsive FEP patients.