The new antipsychotics, and their potential for early intervention in schizophrenia

Over almost four decades, few fundamentally different antipsychotic drugs evolved to challenge classical neuroleptics as the mainstay of the pharmacotherapy of schizophrenia. However, the recent re-emergence of clozapine, together with the emergence of risperidone, portends an increasing number of new antipsychotics which are now either traversing the stages of regulatory approval or else well-advanced in clinical development. This article first evaluates the significance of clozapine and risperidone; it then reviews some of the new antipsychotics and how they might be classified vis-a-vis potential advantages for patients, outlines putative mechanisms and new therapeutic targets, and considers whether such agents may act on any disease process inherent to schizophrenia. One fundamental issue is the extent to which the new antipsychotics might shift materially the risk benefit balance towards intervention, not just at the earliest possible stage following the onset of psychosis but at a yet earlier, 'prodromal' phase of the disorder where there is a considerably greater likelihood of 'treating' behavioural disturbances that prove not to be the harbingers of psychotic illness.