Making sense of norclozapine levels: 3 clinical axioms

Laboratories commonly provide norclozapine concentrations when a plasma clozapine level is requested, but the appropriate use of this information for the treatment of individuals with schizophrenia is not always clear. Particularly vexing is the fact that norclozapine possesses pharmacological properties that are distinct from its parent compound and which contribute to clozapine's efficacy signal, yet the literature focuses primarily on the association of clozapine levels with symptomatic improvement. The purpose of this brief article is to highlight findings with respect to the need to track norclozapine levels, or the ratio of clozapine/norclozapine plasma levels, to optimize efficacy among inadequate responders to clozapine treatment. In addition, there will be a discussion of the specific type of information provided by the clozapine/norclozapine ratio on clozapine's clearance, and how this ratio is sometimes misinterpreted. There is clinical value from to be derived from norclozapine levels and the clozapine/norclozapine ratio for schizophrenia management, and the principles governing use of this information will be distilled into 3 succinct axioms to aid clinicians in managing their clozapine-treated patients with schizophrenia.