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 clozapine and clinical effect is not high, a threshold plasma level of 350-420 ng mL-1 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 clozapine 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.
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 clozapine and clinical effect is not high, a threshold plasma level of 350-420 ng mL-1 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 clozapine 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.
Authors: Eric Olsson; Gunnar Edman; Leif Bertilsson; Dzana Sudic Hukic; Catharina Lavebratt; Sven V Eriksson; Urban Ösby Journal: Prim Care Companion CNS Disord Date: 2015-02-19
Authors: Michael Berk; Joanna Fitzsimons; Timothy Lambert; Christos Pantelis; Jayashri Kulkarni; David Castle; Elizabeth W Ryan; Sean Jespersen; Pat McGorry; Gregor Berger; Bill Kuluris; Tom Callaly; Seetal Dodd Journal: CNS Drugs Date: 2007 Impact factor: 5.749
Authors: Oliver D Howes; Rob McCutcheon; Ofer Agid; Andrea de Bartolomeis; Nico J M van Beveren; Michael L Birnbaum; Michael A P Bloomfield; Rodrigo A Bressan; Robert W Buchanan; William T Carpenter; David J Castle; Leslie Citrome; Zafiris J Daskalakis; Michael Davidson; Richard J Drake; Serdar Dursun; Bjørn H Ebdrup; Helio Elkis; Peter Falkai; W Wolfgang Fleischacker; Ary Gadelha; Fiona Gaughran; Birte Y Glenthøj; Ariel Graff-Guerrero; Jaime E C Hallak; William G Honer; James Kennedy; Bruce J Kinon; Stephen M Lawrie; Jimmy Lee; F Markus Leweke; James H MacCabe; Carolyn B McNabb; Herbert Meltzer; Hans-Jürgen Möller; Shinchiro Nakajima; Christos Pantelis; Tiago Reis Marques; Gary Remington; Susan L Rossell; Bruce R Russell; Cynthia O Siu; Takefumi Suzuki; Iris E Sommer; David Taylor; Neil Thomas; Alp Üçok; Daniel Umbricht; James T R Walters; John Kane; Christoph U Correll Journal: Am J Psychiatry Date: 2016-12-06 Impact factor: 18.112