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Objective: Clozapine is a potent antipsychotic medication with a complex receptor profile. It is reserved for treatment-resistant schizophrenia. We systematically reviewed studies of non-psychosis symptoms of clozapine withdrawal., Methods: CINAHL, Medline, PsycINFO, PubMed, and the Cochrane Database of Systematic Reviews were searched using the keywords 'clozapine,' and 'withdrawal,' or 'supersensitivity,' 'cessation,' 'rebound,' or 'discontinuation'. Studies related to non-psychosis symptoms after clozapine withdrawal were included., Results: Five original studies and 63 case reports / series were included in analysis. In 195 patients included in the five original studies, approximately 20% experienced non-psychosis symptoms following discontinuation of clozapine. In 89 patients in four of the studies, 27 experienced cholinergic rebound, 13 exhibited extrapyramidal symptoms (including tardive dyskinesia), and three had catatonia. In 63 case reports / series included, 72 patients with non-psychosis symptoms were reported, which were catatonia (n=30), dystonia or dyskinesia (n=17), cholinergic rebound (n=11), serotonin syndrome (n=4), mania (n=3), insomnia (n=3), neuroleptic malignant syndrome (NMS) [n=3, one of them had both catatonia and NMS], and de novo obsessive compulsive symptoms (n=2). Restarting clozapine appeared to be the most effective treatment., Conclusions: Non-psychosis symptoms following clozapine withdrawal have important clinical implications. Clinicians should be aware of the possible presentations of symptoms to ensure early recognition and management. Further research is warranted to better characterise the prevalence, risk factors, prognosis, and optimal drug dosing for each withdrawal symptom., Competing Interests: As an editor of the journal, SKW Chan was not involved in the peer review process. Other authors have disclosed no conflicts of interest.

Abstract: In our brief literature review, we discuss the changes in the concept of catatonia as well as its various types and symptoms. We also succinctly review the possible symptoms of clozapine withdrawal. In addition, we analyze the main features of the very few published cases of clozapine withdrawal-induced catatonia and the relationship between neuroleptic malignant syndrome and the malignant subtype of catatonia. Furthermore, we present the case of a 29-year-old male patient with schizophrenia in whom a malignant catatonic episode/neuroleptic malignant syndrome (with negativism, stupor, mutism, autonomic signs [eg, fever, hyperhidrosis], and elevated creatine kinase levels) began 5 days after the patient decided arbitrarily to cease his clozapine treatment. His catatonic symptoms quickly (ie, within a few days) resolved after the reinstitution of clozapine. Finally, we attempt to provide a theoretical explanation for the surprising finding in the literature that the withdrawal of clozapine, unlike the withdrawal of any other antipsychotics, may be associated with catatonia (frequently its malignant subtype). The take-home message of our case is that clinicians should bear in mind the risk of catatonia (especially the malignant subtype of it) after the prompt withdrawal of clozapine therapy., Competing Interests: Conflicts of Interest and Source of Funding: The authors have no conflicts of interest to declare., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

This article presents a case of a 14-year-old female twin with schizophrenia who developed severe catatonia following treatment with olanzapine. Under a combined treatment with amantadine, electroconvulsive therapy (ECT), and (currently) ziprasidone alone she improved markedly. Severity and course of catatonia including treatment response were evaluated with the Bush-Francis Catatonia Rating Scale (BFCRS). This case report emphasizes the benefit of ECT in the treatment of catatonic symptoms in an adolescent patient with schizophrenic illness.

Background: Case reports in which abrupt clozapine discontinuation led to a return of psychosis, autonomic instability, or catatonia have been previously presented in the literature., Objective: The authors report on symptom presentation and resolution in a case of abrupt withdrawal of clozapine medication., Method: The authors describe the condition and history of the patient, a 49-year-old woman with schizophrenia, the medical support she received, and the re-initiation of her clozapine medication., Results: Symptoms of catatonia and autonomic instability resolved by Day 4 of treatment., Conclusion: Patients and their caregivers need to be educated about the effects of abrupt cessation of clozapine administration.

Catatonia as a clozapine withdrawal syndrome has not been documented. We report a case of excited catatonia with fever, autonomic instability, and delirium--a picture of malignant catatonia (lethal catatonia) after abrupt clozapine withdrawal. The use of conventional neuroleptics transformed the excited malignant catatonia into a stuporous state resembling neuroleptic malignant syndrome (NMS). Such a transformation of excited lethal catatonia into NMS has been described in the literature, providing support for the hypothesis that NMS is a variant of catatonia. Opinions, however, have been conflicting whether lethal catatonia and NMS are indistinguishable. We argue that NMS may be regarded as a neuroleptic-induced retarded (stuporous) subtype of malignant catatonia, clinically indistinguishable from nonneuroleptic retarded malignant catatonia but different from the excited form. To differentiate between the two subtypes of malignant catatonia would help resolve the controversy. The nosological status of excited catatonia, a poorly studied condition, remains unclear. The two subtypes of catatonia may differ in pathophysiology and responses to treatment. Clinicians should be alert to catatonia as a possible clozapine withdrawal phenomenon, and excited catatonia deserves more research attention.

We report a case of neuroleptic malignant syndrome where the catatonia clearly followed the administration of neuroleptics and where the neurovegetative disturbance was remarkably severe, including episodes of tracheal spasm, apnoea and episodes of bradycardia, and sinus arrest requiring insertion of a temporary external pacing wire. To our knowledge, such severe disturbance has not previously been reported.