OPTIMIZING TREATMENT WITH CLOZAPINE

Clozapine is the only antipsychotic agent that is effective in treatme nt-resistant schizophrenia. Despite its superior efficacy to chlorprom azine and the fact that it has fewer extrapyramidal side effects than conventional antipsychotics do, clozapine is relatively underused. Thi s may be due in part to a lack of appreciation of clozapine's favorabl e risk-benefit ratio in many patients. In addition, clozapine is only indicated for use in patients who fail to respond adequately to standa rd antipsychotic treatment. Treatment with clozapine considerably impr oves psychiatric well-being and reduces readmission to the hospital an d reduces family burden in many severely ill patients. However, clozap ine is associated with severe side effects, including weight gain, tac hycardia, sedation, seizures, and agranulocytosis. These risks must be weighed against the risks associated with schizophrenia (e.g., suicid e). The death rate attributed to clozapine-induced agranulocytosis has been low, a fact that is largely attributable to safety measures such as the Clozaril National Registry. Determining the optimal dosage for each patient will maximize the benefits of treatment while reducing s ide effects. In some patients, monitoring plasma levels of drug may ai d in optimizing treatment. The optimal plasma level of clozapine is 20 0 to 350 ng/mL. This usually corresponds to a daily dose of 200 to 400 mg, although dosage must be individualized. If patients improve signi ficantly during treatment with clozapine, they should continue to be t reated with clozapine and should be withdrawn from this treatment only when medically warranted. Psychotic relapse rates may be as high as 8 0% among patients switched from clozapine to other novel antipsychotic agents.