The clinical use of clozapine plasma concentrations in the management of treatment-refractory schizophrenia.

The introduction of clozapine into clinical practice represented a major breakthrough in antipsychotic pharmacotherapy. However, in spite of 5 years of use and a extensive research, there has previously been no clinically useful means to predict response to clozapine. Six recent studies have examined the utility of clozapine plasma concentrations in predicting response in treatment-refractory patients with schizophrenia. Five of these studies found that clozapine plasma concentrations above 350 to 420 ng/ml significantly increase the likelihood of clinical response in this patient population. Thus, there is now compelling evidence that clozapine plasma concentrations may play an important role in maximizing the probability of clinical response to clozapine in treatment-refractory schizophrenia. This article provides an overview of studies investigating the relationship between clozapine plasma concentrations and clinical response. The discussion includes guidelines regarding the clinical use of clozapine plasma concentrations in the pharmacological management of persons with treatment-refractory schizophrenia.