Maximizing Clozapine Therapy: Managing Side Effects

Since its introduction to the United States in 1990, the benefits of clozapine use have been repeatedlyvalidated. Clozapine remains the only antipsychotic with proven efficacy in treatment-resistantschizophrenia. Because clozapine has been part of the psychiatric pharmacopeia for considerably lesstime than neuroleptics, which have dominated the field for over 4 decades, its underutilization may bepartly attributed to a lack of experience in managing associated side effects. Most side effects associatedwith clozapine are typical of antipsychotics in general, and with clozapine, these side effects aretypically benign, tolerable, and manageable. It is conceivable that there remains a concern over therisk of agranulocytosis. However, the mandatory blood monitoring carried out through the ClozarilNational Registry has considerably reduced the incidence of fully developed cases of agranulocytosisfrom premarketing values of approximately 1% to 2% to current values of 0.38% and virtually preventedmortalities. These values are likely to decrease further with the application of cytokine augmentationtherapy among patients developing blood dyscrasias. Many side effects of clozapine areobserved early after treatment onset and are greatly reduced by dose adjustments. Appropriate managementof side effects will facilitate a maximization of the benefits of clozapine treatment. Clearly,the benefits of clozapine therapy far outweigh its risks.