The Underuse of Clozapine in Schizophrenia


It has also become apparent that in many situations, clozapine is prematurely discontinued because clinicians are unfamiliar with appropriate management strategies for the variety of possible adverse effects. There is no doubt that this is a medication with a number of potentially serious side effects, but at the same time, it may be the only hope for a patient to sustain hard won gains.

We have reviewed this issue in greater detail elsewhere,6 but the key messages are that ”agranulocytosis, myocarditis, cardiomyopathy, and a QTc interval > 500 milliseconds that is confirmed and derived with the appropriate correction method warrant the immediate discontinuation of clozapine. Clozapine discontnuation with potential rechallenge (provided there is appropriate surveillence and management or prophylactic therapy) is indicated for ileus or subileus, neuroleptic malignant syndrome, venous thromboembolism and diabetic ketoacidosis or hyperosmolar coma.”

In summary, a substantial proportion of patients with schizophrenia experience poor or partial response to antipsychotic medication. Several approaches have been employed in the treatment of such individuals, but clozapine remains the most efficacious. Clozapine is associated with a number of potential adverse effects with which physicians need to be familiar. Despite perceived obstacles and concerns, patients who might benefit deserve a therapeutic trial of clozapine. Further efforts are necessary to increase the appropriate utilization of this treatment.

John M. Kane, MD, is a professor and Chairman of the Department of Psychiatry at the Hofstra North Shore-LIJ School of Medicine. He serves on the Psychiatry Advisor editorial board.


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  3. Kane J, et al. Clozapine for the treatment-resistant schizophrenic. A double-blind comparison with chlorpromazine. Arch Gen Psychiatry. 1988; 45:789.
  4. Essali A, et al. Clozapine versus typical neuroleptic medication for schizophrenia. Cochrane Database Syst Rev. 2009; CD000059.
  5. Nielsen J, et al. Psychiatrists’ attitude towards and knowledge of clozapine treatment. Journal of Psychopharmacology. 2010; 24(7):965-971.
  6. Nielsen J, et al. Termination of clozapine treatment due to medical reasons: when is it warranted and how can it be avoided? J Clin Psychiatry. 2013; 74(6):603-13.