To the Editor: I am writing regarding the article by G. Bondolfi, M.D., and colleagues comparing risperidone and clozapine in treatment-resistant schizophrenia. The authors state that their results should be interpreted with caution because of the limited number of patients in the study.

This study reports on a conglomeration of treatment-resistant and treatment-intolerant patients without distinguishing between the two groups. Therefore, this population is likely quite different from the densely refractory population used to prove clozapine’s efficacy. Some of these patients may not have received the standard low-potency antipsychotics to which they may respond. The lack of rigor with which patients were selected is borne out by the high response rates of over 60% of both groups in this study in the relatively short span of 8 weeks. Previous studies of truly refractory patients have not shown such robust responses. A landmark study by Kane et al. (1) revealed a 30% response rate at 6 weeks in prospectively identified refractory patients treated with clozapine.

My concern is that this study could be used to support the use of risperidone in refractory (as opposed to intolerant) patients, resulting in the delayed use of clozapine. Of greater concern could be its use as a justification to switch patients from clozapine to risperidone, which could lead to serious exacerbations of illness. It is clear that risperidone is an effective antipsychotic that is better tolerated by patients who experience extrapyramidal symptoms while taking standard agents. At present, there is no convincing evidence of its efficacy in treatment-refractory patients. Clozapine remains unique in this regard.