Optimizing treatment with clozapine.

Clozapine is the only antipsychotic agent that is effective in treatment-resistant schizophrenia. Despite its superior efficacy to chlorpromazine and the fact that it has fewer extrapyramidal side effects than conventional antipsychotics do, clozapine is relatively underused. This may be due in part to a lack of appreciation of clozapine's favorable risk-benefit ratio in many patients. In addition, clozapine is only indicated for use in patients who fail to respond adequately to standard antipsychotic treatment. Treatment with clozapine considerably improves psychiatric well-being and reduces readmission to the hospital and reduces family burden in many severely ill patients. However, clozapine is associated with severe side effects, including weight gain, tachycardia, sedation, seizures, and agranulocytosis. These risks must be weighed against the risks associated with schizophrenia (e.g., suicide). 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 side effects. In some patients, monitoring plasma levels of drug may aid in optimizing treatment. The optimal plasma level of clozapine is 200 to 350 ng/mL. This usually corresponds to a daily dose of 200 to 400 mg, although dosage must be individualized. If patients improve significantly during treatment with clozapine, they should continue to be treated with clozapine and should be withdrawn from this treatment only when medically warranted. Psychotic relapse rates may be as high as 80% among patients switched from clozapine to other novel antipsychotic agents.