Differential effectiveness of clozapine for patients nonresponsive to or intolerant of first generation antipsychotic medications.

This report examines whether the gains associated with changing to clozapine are greater for people who have been intolerant of first generation antipsychotic medications versus those who have been treatment-nonresponsive to previous agents. We examined data from an open-label, randomized trial that compared clozapine to usual care with first generation agents (n = 227). While most patients (n = 173, 76%) entered that study because they were nonresponsive to at least two first generation antipsychotic medications (treatment nonresponsive [TNR]), 24 percent (n = 54) were eligible because they experienced intolerable side effects (treatment intolerant [TI]). Significantly more TI patients discontinued their clozapine trial during the 2-year study compared to TNR patients, and TI patients taking clozapine were more likely to develop agranulocytosis or severe leukopenia. However, TI patients who remained on clozapine showed significant reductions in problematic behaviors and greater movement toward independent living situations than TNR patients. Clinicians should give serious consideration to offering clozapine and other second generation antipsychotic medications to patients who have demonstrated intolerance to first generation antipsychotic medications.