Current status of clozapine in the United States.

Abstract

Clozapine is the only antipsychotic in the United States that has been approved by the Food and Drug Administration (FDA) for treatment-resistant schizophrenia. It provides effective treatment even when patients do not respond to other secondgeneration antipsychotics. [1] It also remains the most effective antipsychotic available. No existing first or second-generation antipsychotic has been consistently found to be as effective as clozapine monotherapy in treatment-resistant patients. [2-6] Among patients who entered Phase 2 of the Clinical Antipsychotic Trial of Intervention Effectiveness (CATIE) because of lack of efficacy in Phase 1 of the study, those treated with clozapine (open label) averaged significantly greater time to treatment discontinuation (10.5 months) compared to patients treated with other antipsychotic medications (2.7-3.3 months). At three months, total symptom scores also improved to a significantly greater degree in the clozapine group compared to those treated with risperidone or quetiapine. [7] Similarly, in the open-label, randomized CUtLASS (Cost Utility of the Latest Antipsychotic Drugs in Schizophrenia Study) trial, clozapine treatment was associated with significantly greater improvement in total scores of the Positive and Negative Symptom Scale (PANSS) and better patient subjective ratings compared to risperidone, olanzapine, quetiapine, and amisulpiride. [8] Another large, nonrandomized effectiveness study, the Schizophrenia Outpatient Health Outcomes (SOHO) study, also found clozapine to be superior on clinician and patient ratings at six months compared to other antipsychotics. [9] Based on clinical trials, meta-analyses, and large naturalistic studies clozapine is recommended as the most effective agent in schizophrenia, but the recommendations indicate that it should only be used when other agents fail. [5]