Maximizing clozapine therapy: Managing side effects

Since its introduction to the United States in 1990, the benefits of clozapine use have been repeatedly validated. Clozapine remains the only antipsychotic with proven efficacy in treatment-resistant schizophrenia. Because clozapine has been part of the psychiatric pharmacopeia for considerably less time than neuroleptics, which have dominated the field for over 4 decades, its underutilization may be partly attributed to a lack of experience in managing associated side effects. Most side effects associated with clozapine are typical of antipsychotics in general, and with clozapine, these side effects are typically benign, tolerable, and manageable. It is conceivable that there remains a concern over the risk of agranulocytosis. However, the mandatory blood monitoring carried out through the Clozaril National Registry has considerably reduced the incidence of fully developed cases of agranulocytosis from premarketing values of approximately 1% to 2% to current values of 0.38% and virtually prevented mortalities. These values are likely to decrease further with the application of cytokine augmentation therapy among patients developing blood dyscrasias. Many side effects of clozapine are observed early after treatment onset and are greatly reduced by dose adjustments. Appropriate management of side effects will facilitate a maximization of the benefits of clozapine treatment. Clearly, the benefits of clozapine therapy far outweigh its risks.