The move towards the use of second-generation antipsychotics for the treatment of schizophrenia has provoked much discussion over how to differentiate between the various second-generation agents available on the market. The aim of this review is to provide information that may help clinicians in the decision-making process. The results of comparative studies on general efficacy measures (such as the Positive and Negative Syndrome Scale [PANSS] and the Brief Psychiatric Rating Scale [BPRS]) and comparative studies on cognition do not clearly favour one second-generation agent over another. However, some differences between second-generation agents have become apparent from studies which have examined specific symptoms such as hostility, suicidal ideation and depression/anxiety. There are also differences between second-generation agents with regard to specific aspects of tolerability. For example, in a number of studies olanzapine is associated with fewer extrapyramidal symptoms (EPS) than risperidone, but treatment with risperidone or amisulpride is associated with less weight gain and somnolence. Some studies have investigated the results of switching patients from one antipsychotic agent to another. They have generally reported a successful switch to a second-generation agent.

Overall, there is not enough scientific evidence available to clearly favour one second-generation antipsychotic agent over another in terms of general efficacy or tolerability. Therefore, clinicians must make an individualised treatment decision, and select the most appropriate antipsychotic agent for each patient.