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4 - Discontinuing Clozapine and Management of Cholinergic Rebound

Published online by Cambridge University Press:  19 October 2021

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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References

McCutcheon, R., Beck, K., D’Ambrosio, E., et al. (2018). Antipsychotic plasma levels in the assessment of poor treatment response in schizophrenia. Acta Psychiatrica Scandinavica, 137, 3946.Google Scholar
Horvitz-Lennon, M., Mattke, S., Predmore, Z., et al. (2017). The role of antipsychotic plasma levels in the treatment of schizophrenia. American Journal of Psychiatry, 174, 421426.Google Scholar
Brooks, G. W. (1959). Withdrawal from neuroleptic drugs. American Journal of Psychiatry, 115, 931932.CrossRefGoogle ScholarPubMed
Luchins, D. J., Freed, W. J. and Wyatt, R. J. (1980). The role of cholinergic supersensitivity in the medical symptoms associated with withdrawal of antipsychotic drugs. American Journal of Psychiatry, 137, 13951398.Google Scholar
Lieberman, J. (1981). Cholinergic rebound in neuroleptic withdrawal syndromes. Psychosomatics, 22, 253254.Google Scholar
Shiovitz, T. M., Welke, T. L., Tigel, P. D., et al. (1996). Cholinergic rebound and rapid onset psychosis following abrupt clozapine withdrawal. Schizophrenia Bulletin, 22, 591595.Google Scholar
Eden Evins, A., Demopulos, C., Nierenberg, A., et al. (2006). A double-blind, placebo-controlled trial of adjunctive donepezil in treatment-resistant mania. Bipolar Disorders, 8, 7580.Google Scholar
Stanilla, J. K., de Leon, J. and Simpson, G. M. (1997). Clozapine withdrawal resulting in delirium with psychosis: A report of three cases. Journal of Clinical Psychiatry, 58, 252255.CrossRefGoogle ScholarPubMed
de Leon, J., Odom-White, A., Josiassen, R. C., et al. (2003). Serum antimuscarinic activity during clozapine treatment. Journal of Clinical Psychopharmacology, 23, 336341.Google Scholar
de Leon, J. (2005). Benztropine equivalents for antimuscarinic medication. American Journal of Psychiatry, 162, 627.Google Scholar
Conley, R. R., Tamminga, C. A., Bartko, J. J., et al. (1998). Olanzapine compared with chlorpromazine in treatment-resistant schizophrenia. American Journal of Psychiatry, 155, 914920.CrossRefGoogle ScholarPubMed
Lindenmayer, J. P., Czobor, P., Volavka, J., et al. (2002). Olanzapine in refractory schizophrenia after failure of typical or atypical antipsychotic treatment: An open-label switch study. Journal of Clinical Psychiatry, 63, 931935.Google Scholar
Chengappa, K. N., Pollock, B. G., Parepally, H., et al. (2000). Anticholinergic differences among patients receiving standard clinical doses of olanzapine or clozapine. Journal of Clinical Psychopharmacology, 20, 311316.Google Scholar
Delassus-Guenault, N., Jegouzo, A., Odou, P., et al. (1999). Clozapine–olanzapine: A potentially dangerous switch. A report of two cases. Journal of Clinical Pharmacy and Therapeutics, 24, 191195.Google Scholar
Simpson, G. M. and Meyer, J. M. (1996). Dystonia while changing from clozapine to risperidone. Journal of Clinical Psychopharmacology, 16, 260261.CrossRefGoogle ScholarPubMed
Meltzer, H. Y., Elkis, H., Vanover, K., et al. (2012). Pimavanserin, a selective serotonin (5-HT)2A-inverse agonist, enhances the efficacy and safety of risperidone, 2 mg/day, but does not enhance efficacy of haloperidol, 2 mg/day: Comparison with reference dose risperidone, 6 mg/day. Schizophrenia Research, 141, 144152.CrossRefGoogle Scholar
Hieber, R., Dellenbaugh, T. and Nelson, L. A. (2008). Role of mirtazapine in the treatment of antipsychotic-induced akathisia. Annals of Pharmacotherapy, 42, 841846.CrossRefGoogle ScholarPubMed
Kelly, D. L., Richardson, C. M., Yu, Y., et al. (2006). Plasma concentrations of high-dose olanzapine in a double-blind crossover study. Human Psychopharmacology, 21, 393398.Google Scholar
Meyer, J. M. (2014). A rational approach to employing high plasma levels of antipsychotics for violence associated with schizophrenia: Case vignettes. CNS Spectrums, 19, 432438.Google Scholar
Cummings, J., Isaacson, S., Mills, R., et al. (2014). Pimavanserin for patients with Parkinson’s disease psychosis: A randomised, placebo-controlled phase 3 trial. Lancet, 383, 533540.Google Scholar
Parkinson Study Group. (1999). Low-dose clozapine for the treatment of drug-induced psychosis in Parkinson’s disease. New England Journal of Medicine, 340, 757763.Google Scholar
The French Clozapine Parkinson Study Group. (1999). Clozapine in drug-induced psychosis in Parkinson’s disease. The French Clozapine Parkinson Study Group. Lancet, 353, 20412042.Google Scholar
Weintraub, D., Chiang, C., Kim, H. M., et al. (2016). Association of antipsychotic use with mortality risk in patients with Parkinson Disease. JAMA Neurology, 73, 535541.Google Scholar
Borek, L. L. and Friedman, J. H. (2014). Treating psychosis in movement disorder patients: A review. Expert Opinion on Pharmacotherapy, 15, 15531564.CrossRefGoogle ScholarPubMed
Usui, C., Hatta, K., Doi, N., et al. (2011). Improvements in both psychosis and motor signs in Parkinson’s disease, and changes in regional cerebral blood flow after electroconvulsive therapy. Progress in Neuropsychopharmacology and Biological Psychiatry, 35, 17041708.CrossRefGoogle ScholarPubMed
Lindenmayer, J. P., Citrome, L., Khan, A., et al. (2011). A randomized, double-blind, parallel-group, fixed-dose, clinical trial of quetiapine at 600 versus 1200 mg/d for patients with treatment-resistant schizophrenia or schizoaffective disorder. Journal of Clinical Psychopharmacology, 31, 160168.Google Scholar
Honer, W. G., MacEwan, G. W., Gendron, A., et al. (2012). A randomized, double-blind, placebo-controlled study of the safety and tolerability of high-dose quetiapine in patients with persistent symptoms of schizophrenia or schizoaffective disorder. Journal of Clinical Psychiatry, 73, 1320.Google Scholar
Tonin, F. S., Wiens, A., Fernandez-Llimos, F., et al. (2016). Iloperidone in the treatment of schizophrenia: An evidence-based review of its place in therapy. Core Evidence, 11, 4961.CrossRefGoogle ScholarPubMed
Miyamoto, S., Jarskog, L. F. and Fleischhacker, W. W. (2015). Schizophrenia: When clozapine fails. Current Opinion in Psychiatry, 28, 243248.Google Scholar
Meyer, J. M. (2017). Converting oral to long acting injectable antipsychotics: A guide for the perplexed. CNS Spectrums, 22, 1428.CrossRefGoogle Scholar

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