Cited by 105Schizophrenia research and treatmentNeurotransmitter Receptor Influence on BehaviorTreatment of Major Depression

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Cholinergic Rebound and Rapid Onset Psychosis Following Abrupt Clozapine Withdrawal

Shiovitz, T. M., Welke, T. L., Tigel, P. D., Anand, R., Hartman, R. D., Sramek, J. J., Kurtz, N. M., Cutler, N. R.·1996·Schizophrenia Bulletin

DOI 10.1093/schbul/22.4.591

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Abstract

Following the conduct of a 28-day inpatient bioequivalence study of clozapine in schizophrenia patients, withdrawal effects after abrupt discontinuation from clozapine were assessed. Thirty patients who met DSM-III-R criteria for schizophrenia, residual type, or schizophrenia in remission were enrolled in the study. Patients were evaluated for symptoms of withdrawal effects for 7 days after clozapine 200 mg/day was abruptly withdrawn. Of 28 patients who completed the study, 11 had no withdrawal symptoms; 12 had mild withdrawal adverse events of agitation, headache, or nausea; four patients experienced moderate withdrawal adverse events of nausea, vomiting, or diarrhea; and one patient experienced a rapid-onset psychotic episode requiring hospitalization. Cholinergic rebound is a likely explanation for the mild to moderate withdrawal symptoms and is easily treated with an anticholinergic agent. Mesolimbic supersensitivity, as well as specific properties of clozapine, are discussed as likely causes for rapidonset psychosis. Our findings are consistent with previous reports of withdrawal reactions associated with clozapine, further reminding clinicians to monitor patients closely following abrupt discontinuation of clozapine.

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Wong, O., Fung, H., & Lam, T. (2010) · Hong Kong Journal of Emergency Medicine · doi:10.1177/102490791001700210 · Cited by 2
“For those patients with moderate or severe symptoms, the onset time ranged from 24 hours to 3 days.(23) Rapid improvement of delirium and psychotic symptoms”
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Amisülpirid Kesilmesini İzleyen Okülerjik Krizin Eşlik Ettiği Psikotik Alevlenme: Olgu Sunumu
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McCullough, A., Stroup, J. S., & Brahm, N. C. (2013) · Journal of Pharmacy Technology · doi:10.1177/8755122513500917 · Cited by 1
“Symptoms include gastric upset (nausea, vomiting, and diarrhea), agitation, psychosis, sialorrhea, and diaphoresis.(11) These were not noted in our patient.”
Background
Antipsychotics: Clinical Effectiveness
Freudenreich, O. (2019) · Current clinical psychiatry · doi:10.1007/978-3-030-29450-2_16 · Cited by 1
Use of Clozapine in the General Hospital
Mustafa, F. A. (2025) · Psychopharmacology Bulletin · doi:10.64719/pb.4617 · Cited by 1
Rapid-Onset Psychosis and Cholinergic Rebound After Abrupt Discontinuation of Clozapine
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Overdiagnosis and Underdiagnosis of Bipolar Disorder
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Schizophrenia Bulletin Index: 1996-97
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Discontinuing Clozapine and Management of Cholinergic Rebound
Meyer, J. M., & Stahl, S. M. (2019) · Cambridge University Press eBooks · doi:10.1017/9781108553575.006

Authors: Shiovitz, T. M., Welke, T. L., Tigel, P. D., Anand, R., Hartman, R. D., Sramek, J. J., Kurtz, N. M., & Cutler, N. R.
Affiliations: Clinical Trials of Texas (US)
Worldwide Clinical Trials (United States) (US)
Corresponding author: Shiovitz, T. M.
Cutler, N. R.
ORCID: Anand, R.
Hartman, R. D.
Sramek, J. J.
Cutler, N. R.
Venue: Schizophrenia Bulletin
Publisher: Oxford University Press (OUP)
Published: 1996-01-01
Volume: 22
Issue: 4
Pages: 591-595
ISSN: 0586-7614 (ISSN-L)
1745-1701
DOI: 10.1093/schbul/22.4.591
OpenAlex: W2137941062
Semantic Scholar: f2d25e1e9ea9112b298df79e9e1d15f8eafa939c
Cited by: 104
References: 2
Citations by year: 2026: 3 · 2025: 4 · 2024: 3 · 2023: 5 · 2022: 2 · 2021: 7 · 2020: 3 · 2019: 8 · 2018: 2 · 2017: 4 · 2016: 1 · 2015: 4 · 2013: 5 · 2012: 2
FWCI: 2.84
Type: journal article
Language: en
Open access: closed
Locations: Schizophrenia Bulletin (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
Keywords: clozapine, drug withdrawal
MeSH terms: Adolescent, Adult, Clozapine, Diarrhea, Dose-Response Relationship, Drug, Female, Humans, Male, Middle Aged, Nausea, Neurologic Examination, Psychoses, Substance-Induced, Receptors, Cholinergic, Schizophrenia, Schizophrenic Psychology, Substance Withdrawal Syndrome, Antipsychotic Agents, Vomiting, Akathisia, Drug-Induced

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Cholinergic Rebound and Rapid Onset Psychosis Following Abrupt Clozapine Withdrawal

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