The Clinical Use of Plasma Clozapine Levels

Abstract

Objective: This review examines the evidence supporting the proposition that a threshold clozapine plasma level can predict clinical response. In addition, it provides a brief overview of the pharmacokinetics, side effects, drug interactions and assay methodology of clozapine.

Method: A comprehensive search of relevant literature was made with respect to the above criteria. The findings were collated and analysed to produce an overview of the usefulness of using clozapine levels in clinical practice. Results: Most researchers find that, although the correlation between dose of cloza pine and clinical effect is not high, a threshold plasma level of 350–420 ng mL of clozapine is associated with an increased probability of a good clinical response to the drug. Results vary, however, with the study design.

Conclusions: The data reviewed present a case for increasing the dose of cloz apine in non-responsive patients to achieve a plasma level of at least 350–420 ng mL⁻¹. Non-response at these levels, however, should not preclude a further upward titration of dose. This should occur unless (i) clinical response is obtained at a lower dose, (ii) intolerable side effects occur, or (iii) a daily dose of 900 mg is reached.