When should clozapine be initiated in schizophrenia?: Some arguments for and against earlier use of clozapine.

Clozapine is one of the original atypical antipsychotics. It was withdrawn from the market in 1974 because of haematological safety concerns, but since 1989 has enjoyed a renaissance for the management of treatment-resistant schizophrenia under systems where case registration allows regular haematological monitoring. Clozapine continues to show enduring superiority across many aspects of the clinical pharmacology of the treatment of schizophrenia, e.g. it has specific anti-suicidal properties and recent broader trials have shown continuing superiority in wide groups of patients. This article considers some of the arguments for unshackling clozapine from its current license for schizophrenia (its superiority overall in treatment-resistant schizophrenia, its potential for use in first-episode patients, and its anti-suicidal potential), and tries to synthesise these into some of the national guidelines available for the treatment of schizophrenia.