Clinical Response to Clozapine in Patients With Schizophrenia

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Abstract
One of the take-home messages from our recent report regarding the clinical and biological effects of the atypical neuroleptic, clozapine, was that the admixture of clozapine's effects on dopaminergic, serotonergic, and noradrenergic systems may underlie its unique efficacy in otherwise poorly responsive patients with schizophrenia.1We agree with a suggestion by R. W. Pies, MD, (unpublished communication to theArchives, May 1992) that clozapine's diverse pharmacologic properties indicate strategies for augmentation of neuroleptic drugs in treatment-resistant patients and that thioridazine or mesoridazine besylate may be particularly useful, given their relatively low incidence of extrapyramidal side effects. Whereas much attention has been given to the 5-hydroxytryptamine2(5-HT2) antagonism of clozapine, including the ratio of 5-HT2to D2affinities as a predictor of neuroleptic atypicality,2we have noted that clozapine's relatively potent α2-antagonism (putatively contributing to observed increases in norepinephrine turnover) is distinct among

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