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Clozapine plasma levels and dosing strategies in patients with treatment-refractory schizophrenia

Published online by Cambridge University Press:  13 June 2014

Peter F Buckley
Affiliation:
Department of Psychiatry, Case Western Reserve University, University Hospitals of Cleveland, Hanna Pavilion, 2040 Abington Road, Cleveland, Ohio 44106, USA
Philip Cola
Affiliation:
Department of Psychiatry, Case Western Reserve University, School of Medicine, Cleveland, Ohio 44106, USA
Mitsuru Hasegawa
Affiliation:
Department of Psychiatry, Case Western Reserve University, School of Medicine, Cleveland, Ohio 44106, USA
Christine Lys
Affiliation:
Department of Psychiatry, Case Western Reserve University, School of Medicine, Cleveland, Ohio 44106, USA
Paul Thompson
Affiliation:
Department of Psychiatry, Case Western Reserve University, School of Medicine, Cleveland, Ohio 44106, USA

Abstract

Objective: To determine the effect on clinical response to clozapine of increasing the plasma levels of clozapine and its major metabolite N-desmethylclozapine in 19 patients with schizophrenia who had plasma clozapine levels ≤ 370ng/ml, a level previously determined to identify patients who were unlikely to have an adequate response to clozapine.

Method: The dosage of clozapine was increased by 20% in 11 patients and left unaltered in the other eight patients. Clozapine and N-desmethylclozapine plasma levels were measured after six weeks at the higher dose.

Results: Nine of the 11 patients in whom clozapine dosage was increased subsequently achieved plasma clozapine levels ≥ 370ng/ml. However, in this group of patients who already had partially responded to clozapine, increasing the dosage of clozapine did not produce additional clinical improvement.

Conclusion: Clozapine plasma levels are useful in clinical practice to guide dosage strategies. However, these results suggest that increasing the dosage of clozapine to achieve plasma levels ≥ 370ng/ml is unlikely to produce further improvement in patients who have already achieved a partial response to clozapine at plasma levels ≤ 370ng/ml.

Type
Original Papers
Copyright
Copyright © Cambridge University Press 1997

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