LAUSR

To the Editors: C lozapine is the only antipsychotic medication that is indicated for use in treatment-resistant schizophrenia (TRS), which has an estimated prevalence of 20% to 30%. The true level of TRSmay be lower because of issues such as subtherapeutic plasma levels and medication noncompliance. Accordingly, one would expect it to be offered to a little less than 20% to 30% of all patients with schizophrenia, but the reality is quite different. It seems to be underprescribed in many countries although there are huge geographical differences in its use. It is important to understand the reasons underlying this underprescription of clozapine in many countries. Concerns, on the part of patients, clinicians and caretakers, about the risk of agranulocytosis and the burden of neutrophil blood monitoring may be two of the major reasons why clozapine is not being prescribed more. Other reasonswhy clozapine is underprescribed may include potential adverse effects, such as seizures, constipation, ileus, sedation, weight gain, risk of diabetes, hypersalivation, and myocarditis. The therapeutic dose of clozapine can differ a lot between patients and high serum levels of clozapine increase the risk of adverse effects, especially seizures. Therefore, it is important to monitor serum clozapine to minimize adverse effects and not only focus on the neutrophil count. Most people have difficulty in working with and understanding very low risks. To make informed treatment decisions in TRS, the truly low risk of dying from agranulocytosis must be weighed against the potential benefits of clozapine, including the substantial reduction in mortality associated with clozapine treatment, which far outweighs the risk of death from agranulocytosis. The risk of developing agranulocytosis has been estimated to be approximately 0.7%, and in 3% of cases, agranulocytosis has a lethal outcome. That translates to a lethal outcome of 0.02% or 2 of every 10,000 patients. As most of the risk of agranulocytosis occurs during the first half year of treatment, a lethal outcome drops to 0.004%