Clozapine withdrawal emergent myoclonus: A case series

Background: Catatonia has been reported with withdrawal of medications. Among the various psychotropics, clozapine has been implicated to cause catatonia when abruptly withdrawn. The data regarding clozapine withdrawal catatonia are scarce and are mostly available in the form of case reports and series. Aim: In this case series, we present three cases of clozapine withdrawal catatonia and review the available literature on clozapine withdrawal clozapine. Results: All the three patients developed catatonia within 48 h to 14 days of stoppage of clozapine in the doses of 100–350 mg/day. Two of the patients experiencing clozapine withdrawal improved with reinstitution of clozapine in the previous doses along with benzodiazepines. However, one patient additionally required electroconvulsive therapy (ECT) for the management of withdrawal catatonia. A review of literature showed that clozapine withdrawal catatonia has male preponderance and has been reported with withdrawal of clozapine doses of 50–550 mg/day. The catatonia usually starts in 48 h to 2 weeks of stopping clozapine. Available literature suggests that most of the patients have been managed with restarting of clozapine, along with lorazepam and occasional patients require ECT. Conclusions: To conclude our case series and the available review of literature suggests that sudden discontinuation of clozapine can lead to withdrawal catatonia. Our cases also highlight the importance of reviewing treatment history, especially of abrupt discontinuation of clozapine when a patient on clozapine present with catatonia. This can be very helpful in deciding about further management.

Catatonia is a neuropsychiatric disorder characterised by altered movement, speech, and behaviour. Clozapine is an established therapy for treatment-resistant schizophrenia, but its role in catatonia has not been systematically examined. In this systematic review, we aimed to assess the evidence for clozapine as a treatment for catatonia.Full text original research articles in English where at least one patient with catatonia was treated with clozapine were included, provided catatonia did not occur solely in the context of neuroleptic malignant syndrome. Results were tabulated with calculations of summary statistics presented. Risk of bias was assessed with the Tool for Evaluating the Methodological Quality of Case Reports and Case Series.182 patients were included, 81 from cohort studies and 101 from case reports or case series. 119/182 patients (65 %) had a specified underlying diagnosis of schizophrenia. Over 80 % of reported patients with catatonia had at least partial remission following treatment with clozapine across both cohort studies and case reports and case series. Among the case reports and series, 24/101 patients (23.8 %) followed clozapine withdrawal. Overall, 25 studies were of low quality, 60 of moderate quality and 8 of high quality.Our findings should be interpreted with caution, as the reliance on case reports, case series and small cohort studies is susceptible to reporting biases, regression to the mean and confounding by other treatments. Future research could use large healthcare databases to ascertain outcomes in those on clozapine with a history of catatonia given the difficulty and expense of conducting randomised controlled trials.

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