Management of rhabdomyolysis in a patient treated with Clozapine: a case report and clinical recommendations
Laurent Bechard 1, 2*, Olivier Corbeil 1, 2, Marc-Andre Thivierge 1, Ibrahim Assaad 1, Camille Boulanger 1, Marie-Pierre Mailhot 2, 4, Alexis Turgeon-Fournier 5, 6, Marc-Andre Roy 2, 3, 4, Marie-France Demers 1, 2, 3
1Faculty of pharmacy, Université Laval, 1050, avenue de la Médecine, G1V 0A6, Québec City (Québec), Canada., 2Clinique Notre-Dame-des-Victoires, Institut universitaire en santé mentale de Québec, 2525, chemin de la Canardière, Entrée #A-1-2, G1J 2G3, Québec City (Québec), Canada., 3CERVO research center, 2601, chemin de la Canardière, G1E 1T2, Québec City (Québec), Canada., 4Department of psychiatry et neurosciences, Faculté de médecine, Université Laval, 1050, avenue de la Médecine, G1V 0A6, Québec City (Québec), Canada., 5Department of Anesthesiology and Critical Care Medicine, Division of Critical Care Medicine, Université Laval, G1J 1Z4, Québec City (Québec), Canada., 6Department of Anesthesiology & Department of Medicine, Population Health and Optimal Health Practices Research Unit (Trauma - Emergency - Critical Care Medicine), CHU de Québec - Université Laval Research Center, G1S 4L8, Québec, Canada
Received: February 12, 2021; Revised: April 8, 2021; Accepted: June 14, 2021; Published online: June 14, 2021.
© The Korean College of Neuropsychopharmacology. All rights reserved.

Abstract
Clozapine has a unique efficacy in treatment-resistant schizophrenia. Its use is, however, associated with potential adverse events. Among those, clozapine induced rhabdomyolysis can compromise clozapine treatment. Recommendations surrounding the management of this rare adverse event are limited. We present a case of clozapine-induced rhabdomyolysis. A 20-year-old Caucasian male diagnosed with resistant schizophrenia developed, after a 5-month total exposition and a significant response to treatment, a marked creatine kinase (CK) elevation and important myalgia in the weeks following an increment from 175 to 200 mg of the daily dose of clozapine. This event also coincided with weight training as reported by the patient. The patient was hospitalized, and the clozapine was stopped following the diagnosis of rhabdomyolysis (CK 45564 U/L). The cause of rhabdomyolysis was thoroughly investigated, and clozapine was held accountable for most. Clozapine cessation led to a severe psychotic relapse. Clozapine rechallenge while strictly monitoring CK was then performed allowing a significant clinical response. Clozapine was pursued despite two other episodes of mild CK elevations observed following weight training. Rhabdomyolysis comes as a rare adverse event of clozapine and its mechanism is poorly understood. Evidence on clozapine rechallenge following this adverse event is lacking and the innocuity of such practice is unknown. The unique aspect of our case report is that a shared decision with the medical team, patient and family led to a proactive clozapine rechallenge. More research is needed to provide robust guidelines and evidenced based approaches for clinicians in such a clinical dilemma.
Keywords: Rhabdomyolysis, Clozapine, Creatine Kinase, Schizophrenia, Rechallenge


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