CLOZAPINE - A REVIEW OF ITS PHARMACOLOGICAL PROPERTIES AND THERAPEUTIC USE IN PATIENTS WITH SCHIZOPHRENIA WHO ARE UNRESPONSIVE TO OR INTOLERANT OF CLASSICAL ANTIPSYCHOTIC AGENTS

Clozapine is an atypical antipsychotic agent whose mode of action is thought to pertain to its interactions with dopamine and serotonin (5-hydroxytryptamine) neurotransmitter systems. Clinical efficacy may be related to plasma clozapine concentrations. Response rates have varied widely on short term therapy (30 to 100%); during longer term treatment, 60% of patients unresponsive to or intolerant of previous antipsychotic therapy responded to clozapine. Significant improvement in both positive and negative psychotic symptoms, quality of life, social functioning and suicidality has been demonstrated Clozapine has demonstrated superior efficacy to that of chlorpromazine, haloperidol and fluphenazine in treatment-resistant patients, and improvements were maintained with long term treatment. Economic savings may be realised after the first 1 to 2 years of clozapine therapy. Extrapyramidal symptoms occur less frequently and appear to be less severe in patients receiving clozapine than in those receiving classical antipsychotic agents. The incidence of tardive dyskinesia and neuroleptic malignant syndrome is very low. Agranulocytosis appears to occur in about 0.8% of clozapine recipients, and the incidence has been reported to decrease after the first year of therapy. Regular blood monitoring is mandatory. More frequent adverse events associated with clozapine include tachycardia, sedation, hypersalivation and orthostatic hypotension. With regular blood monitoring, clozapine is the drug of choice for patients with schizophrenia who are unresponsive to or intolerant of previous antipsychotic therapy.