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4 - Discontinuing Clozapine and Management of Cholinergic Rebound

Published online by Cambridge University Press:  19 October 2021

Jonathan M. Meyer  and
Stephen M. Stahl
Jonathan M. Meyer
Affiliation:
University of California, San Diego
Stephen M. Stahl
Affiliation:
University of California, San Diego
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Summary

The need to discontinue clozapine is a lamentable but medically necessary event in certain circumstances, and at times must be accomplished abruptly. In instances when the patient can be tapered off gradually (e.g. dilated cardiomyopathy), the risk of cholinergic rebound symptoms is lessened and the clinician can focus on making an informed choice about antipsychotic treatment. Although no agent equals clozapine’s efficacy for treatment-resistant schizophrenia, 35% of a group of schizophrenia outpatients with poor antipsychotic response (n = 99) who were considered candidates for clozapine had subtherapeutic plasma levels of their current antipsychotic. Thus, a certain fraction of patients who end up on clozapine were failures due to inadequate dosing of prior antipsychotics, poor adherence or kinetic issues. As will be discussed below, this is an important consideration for patients deemed treatment-resistant but who did not experience adverse effects of prior antipsychotic treatment, particularly those related to D2 antagonism. This understanding may open the door to revisiting prior antipsychotics, but with careful monitoring of adherence and drug exposure via use of plasma levels.

Type
Chapter
Information
The Clozapine Handbook
Stahl's Handbooks
 , pp. 78 - 89
Publisher: Cambridge University Press
Print publication year: 2019

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