The Underuse of Clozapine in Schizophrenia


Despite the high prevalence of treatment refractory illness, the use of clozapine — the one medication that has shown to be efficacious in a substantial proportion of such patients3,4 — remains strikingly low in many countries around the world, particularly the United States. In order to promote more appropriate levels of utilization, it is important to understand the potential obstacles. I believe that the problem starts with physicians rather than patients, as many of the former do not even present clozapine as an option to the latter.

In one survey of psychiatrists in Denmark with more than five years of clinical experience, it was reported that: 7 of the 100 individuals interviewed had never prescribed clozapine; 65 % would rather prescribe two antipsychotics than clozapine; 85 % knew that according to guidelines clozapine should be initiated after failure of two or three antpsychotics; 66 % believed that clozapine patients were less satisfied with their treatment than patients treated with other antipsychotics; and 28 % of psychiatrists would not use more than 600mg./day.5

In an unpublished survey that my colleagues and I conducted among 171 attending and resident psychiatrists on the staff of our hospital (The Zucker Hillside Hospital in New York City), we found that concern about patient adherence with the medication and with required blood monitoring, as well as potential patient refusal to try clozapine, topped the list of reasons for physician hesitation to recommend.

The unfortunate aspect of these findings is that physicians’ assumptions about patient attitudes is often not accurate and unless patients are provided an informed opportunty to participate in shared decision-making, they can be missing out on a strongly desired therapuetic benefit.

In our view, patients will have difficulty evaluating the potential benefits of clozapine until they have experienced first hand how it might effect their own illness after a three to six month therapuetic trial. Because clozapine represents the only option with proven efficacy for treatment resistant patients,  it is particularly unfortunate for us to deprive a patient of that possible choice and opportunity.