Recurrent clozapine and lorazepam withdrawal psychosis with catatonia

Wang, Bob Z.; Gupta, Arun; Bastiampillai, Tarun; Sani, Fariza

doi:10.1177/0004867412444992

Cited by 14 publications

(8 citation statements)

References 7 publications

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“…Twenty articles 29 , 30 , 44 , 46 , 49 – 64 described 20 cases of clozapine withdrawal catatonia (Table 2 ). The average patient age was 41 years old (range 22−61 years) and the male to female ratio was 1.22:1.…”

Section: Resultsmentioning

confidence: 99%

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Review of withdrawal catatonia: what does this reveal about clozapine?

2018

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Withdrawal symptoms are common upon discontinuation of psychiatric medications. Catatonia, a neuropsychiatric condition proposed to be associated with gamma-aminobutyric acid (GABA) hypoactivity due to its robust response to benzodiazepines, has been described as a withdrawal syndrome in case reports but is not a well-recognized phenomenon. The authors undertook a review of withdrawal catatonia with an aim to understand its presentation as well as the medications and psychoactive substances it is associated with. The review identified 55 cases of withdrawal catatonia, the majority of which occurred upon discontinuation of benzodiazepines (24 cases) and discontinuation of clozapine (20 cases). No other antipsychotic medications were identified as having been associated with the onset of a catatonic episode within 2 weeks following their discontinuation. Increasing GABA activity and resultant GABA receptor adaptations with prolonged use is postulated as a shared pharmacological mechanism between clozapine and benzodiazepines that underlie their association with withdrawal catatonia. The existing evidence for clozapine’s activity on the GABA system is reviewed. The clinical presentations of benzodiazepine withdrawal catatonia and clozapine withdrawal catatonia appear to differ and reasons for this are explored. One reason is that benzodiazepines act directly on GABAA receptors as allosteric agonists, while clozapine has more complex and indirect interactions, primarily through effects on receptors located on GABA interneurons. Another possible reason for the difference in clinical presentation is that clozapine withdrawal catatonia may also involve receptor adaptations in non-GABA receptors such as dopamine and acetylcholine. The findings from our review have implications for the treatment of withdrawal catatonia, and treatment recommendations are provided. Further research understanding the uniqueness of clozapine withdrawal catatonia among antipsychotic medication may give some insight as to clozapine’s differential mechanism of action.

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Section: Resultsmentioning

confidence: 99%

“…One case report described a patient who experienced catatonia on withdrawal of clozapine and later on withdrawal of benzodiazepines independent of each other 44 . It was therefore included in both sections of the results.…”

Section: Resultsmentioning

confidence: 99%

Review of withdrawal catatonia: what does this reveal about clozapine?

2018

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“…In 2 of the 9 cases, we were unable to make the catatonia diagnosis for the reduced number of symptoms described in the published articles [22, 23]. In the remaining 7 cases [15–21], the authors described ≥3 DSM-5 catatonia symptoms (Table 2). …”

Section: Discussionmentioning

confidence: 99%

Catatonia Secondary to Sudden Clozapine Withdrawal: A Case with Three Repeated Episodes and a Literature Review

Bilbily

McCollum

Leon

2017

Case Reports in Psychiatry

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A literature search identified 9 previously published cases that were considered as possible cases of catatonia secondary to sudden clozapine withdrawal. Two of these 9 cases did not provide enough information to make a diagnosis of catatonia according to the Diagnostic and Statistical Manual, 5th Edition (DSM-5). The Liverpool Adverse Drug Reaction (ADR) Causality Scale was modified to assess ADRs secondary to drug withdrawal. From the 7 published cases which met DSM-5 catatonia criteria, using the modified scale, we established that 3 were definitive and 4 were probable cases of catatonia secondary to clozapine withdrawal. A new definitive case is described with three catatonic episodes which (1) occurred after sudden discontinuation of clozapine in the context of decades of follow-up, (2) had ≥3 of 12 DSM-5 catatonic symptoms and serum creatinine kinase elevation, and (3) required medical hospitalization and intravenous fluids. Clozapine may be a gamma-aminobutyric acid (GABA) receptor agonist; sudden clozapine withdrawal may explain a sudden decrease in GABA activity that may contribute to the development of catatonic symptoms in vulnerable patients. Based on the limited information from these cases, the pharmacological treatment for catatonia secondary to sudden clozapine withdrawal can include benzodiazepines and/or restarting clozapine.

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“…It was here confirmed, on a large-scale basis, that, following the abrupt reduction of clozapine dosage a discontinuation/withdrawal syndrome may occur. This may involve possible severe and long-lasting symptoms [10,59,67,84]. Moreover, although this may be an unusual event, it is here suggested that cases of misuse/abuse/dependence could occur in patients with a concomitant SUD and this is despite clozapine being of clinical value for the treatment of dual diagnosis.…”

Section: Discussionmentioning

confidence: 82%

“…The clozapine multi-receptor agonism/antagonism is likely responsible for the occurrence of discontinuation/withdrawal symptoms. Indeed, the clozapine pharmacodynamic profile may well include: (a) a dopaminergic super-sensitivity, with the risk of a dopaminergic psychosis and symptoms such as dystonias, dyskinesias, and catatonia [38,[56][57][58][59]; (b) a cholinergic rebound, inducing in vulnerable patients a rapid worsening of psychosis, agitation, confusion, insomnia, and symptoms including nausea, vomiting, diarrhea, headache, diaphoresis, and abnormal movements, such as dystonias and dyskinesias [6,54,56,57,[60][61][62][63][64]. Consistent with this, symptoms appear to regress rapidly with the help of anti-cholinergic drugs; (c) a serotonergic syndrome, which may occur even without the concomitant use of a serotonergic agent [10,39,61].…”

Section: Discussionmentioning

confidence: 99%

Focus on Clozapine Withdrawal- and Misuse-Related Cases as Reported to the European Medicines Agency (EMA) Pharmacovigilance Database

et al. 2020

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Background: Clozapine is of high clinical relevance for the management of both treatment-resistant schizophrenia and psychotic disturbances with concurrent drug misuse. Although the molecule presents with a range of well-known side-effects, its discontinuation/withdrawal syndrome has been only anecdotally described. Aims: the 2005–2018 European Medicines Agency (EMA) dataset of Adverse Drug Reactions (ADRs) was analyzed to identify and describe possible clozapine withdrawal- and misuse-/abuse-/dependence-related issues. Method: A descriptive analysis of clozapine-related ADRs was performed when available, data on ADRs’ outcome, dosage, and possible concomitant drug(s) were considered. Results: Out of 11,847 clozapine-related ADRs, some 599 (5.05%) were related to misuse/abuse/dependence/withdrawal issues, including 258 withdrawal-related (43.1%); 241 abuse-related (40.2%); and 80 intentional product misuse-related (13.3%) ADRs. A small number of overdose- and suicide-related ADRs were reported as well. Clozapine was typically (69.2%) identified alone, and most (84.7%) fatalities/high-dosage intake instances were reported in association with a history of substance abuse. Conclusions: Previous suggestions about the possibility of a clozapine discontinuation/withdrawal occurrence are here supported, but further studies are needed. However, the misuse/abuse cases here identified might be difficult to interpret, given the lack of studies highlighting the possible recreational use of clozapine. The high-dosage intake, fatal outcomes and clozapine/polydrug abuse issues reported here may, however, be a reason for concern.

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Recurrent clozapine and lorazepam withdrawal psychosis with catatonia

Cited by 14 publications

References 7 publications

Review of withdrawal catatonia: what does this reveal about clozapine?

Review of withdrawal catatonia: what does this reveal about clozapine?

Catatonia Secondary to Sudden Clozapine Withdrawal: A Case with Three Repeated Episodes and a Literature Review

Focus on Clozapine Withdrawal- and Misuse-Related Cases as Reported to the European Medicines Agency (EMA) Pharmacovigilance Database

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