A historical perspective of clozapine.

Having challenged the established view that extrapyramidal symptoms are an intrinsic feature of antipsychotic activity, clozapine was developed as the first atypical antipsychotic with activity against both the positive and negative symptoms of schizophrenia. Following its partial withdrawal due to concerns over agranulocytosis, clozapine was reintroduced in response to pressure from psychiatrists and is now used worldwide in patients with treatment-resistant schizophrenia, having demonstrated its superiority over typical antipsychotic agents. This, combined with its low propensity to cause tardive dyskinesia, has transformed the management of patients with schizophrenia. This article outlines the history of clozapine's development, from its discovery in 1958 to its current position as the "gold standard" therapy for treatment-resistant schizophrenia.