Case Report

An uncommonly recognized cause of rhabdomyolysis after quetiapine intoxication

Abstract

Antipsychotics can cause acute rhabdomyolysis (RM) as part of a neuroleptic malignant syndrome or via a direct toxic effect on myocytes. Such a serious adverse effect has been rarely linked to quetiapine treatment. This report highlights a different pathophysiology of RM after quetia- pine overdosing with suicidal intent. The 44-year-old patient had schizophrenia and took 9000 mg, 10 times his daily dosage. He became somnolent and later unconscious. After lying for 14 hours on a firm mattress probably motionless, he was difficult to arouse next morning and could hardly walk. In the emergency department (ED), brown urine and a Creatinine kinase (CK) of 30 660 U/L were detected. Rhabdomyolysis was treated successfully with plasma expansion. A compartment syndrome led to bilateral peroneal paresis. A direct toxic effect of quetiapine on myocytes as claimed in the past is unlikely because, after reexposure to quetiapine 3 months later, CK remained normal. It is recommended that every patient who overdosed on quetiapine should be thoroughly assessed in ED including measurement of CK to detect RM due to long immobility early and avoid acute renal failure.

Quetiapine is the number one antipsychotic used for overdosing with suicidal intent in Wales (clozapine excluded) [1]. All atypical antipsychotics including quetia- pine can cause rhabdomyolysis (RM) in the neuroleptic malignant syndrome (NMS). One suggested mechanism for RM in the absence of NMS is an increase of skeletal muscle cell membrane permeability in Vulnerable subjects [2]. This report describes a 44-year-old man of Turkish descent who took 9000 mg of quetiapine with suicidal intent. He had been treated for 22 years for schizophrenia with different antipsychotics until he was started at the age of 40 years on quetiapine monotherapy. Before he overdosed, his prescribed dosage varied between 300 and 600 mg twice daily, which he took irregularly without symptoms of myalgia. One day before admission to the emergency department (ED), he took 30 tablets of quetiapine 300 mg to end his suffering. He became

somnolent, lay down on his firm couch, and became unconscious at around 7:00 PM. Next morning, he was found motionless and difficult to arouse. A psychiatric nurse initially thought that observation and outpatient treatment might suffice, but the psychiatrist advised to take him to the ED. After probably lying motionless for 17 hours, he stood up and staggered to the ambulance at noon. In the ED, his brown urine was noted; and a massive elevation of creatinine kinase (CK) to 11 000 U/L was detected. He was given intravenous isotonic saline to expand plasma volume, but the CK continued to rise during the next 12 hours to 30 660 U/L until it dropped to 224 U/L over the next 2 days. Renal failure did not occur.

No clinical signs of an NMS were found. A prominent swelling of both lower legs with tense overlying skin and bilateral peroneal nerve palsy led to a diagnosis of compartment syndrome. The patient’s mental status showed his unchanged paranoid-hallucinatory syndrome. He was able to walk with assistance with typical bilateral foot drop. A diagnosis of RM due to immobilization in coma was made. Ten days after admission, the CK was back to normal. He was started on amisulpride up to 200 mg twice daily and, later, aripiprazole 30 mg once daily. Four months after hospital admission, aripiprazole was stopped; and quetiapine 900 mg daily was restarted. During 3 months of quetiapine treatment, CK remained normal.

This case report illustrates a probably unrecognized complication of quetiapine overdosing. Quetiapine has a strong sedating effect. Although quetiapine is regarded as a safe drug with low toxicity, one case of death after ingestion of 6000 mg has been reported. However, survival after 30 000 mg has also been reported [3].

A dose of 9000 mg can certainly lead to a stupor with immobility. It is well known that immobility for many hours is a cause of RM.

Smith et al [4] reported on a similar case where a young man lay unconscious on the floor after ingesting 12 000 mg of quetiapine with an increase of CK to 47 663 U/l, but attributed the RM to a direct toxic effect of quetiapine because they believed such high CK peaks to be uncommon due to immobility in coma. Melli et al [5] calculated the mean increase of CK in drug-induced RM as 12 936 U/L and in immobility-associated RM as 17 163 IU/L.

It is recommended that every patient who overdosed on quetiapine should be thoroughly assessed in ED including

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1060.e2 Case Report

measurement of CK to detect RM due to long immobility early and avoid acute renal failure.

Julian Robert Mario Dickmann Brasenose College, Oxford, OX1 4AJ, United Kingdom E-mail address: [email protected]

Laura Maria Dickmann Goethe Universitat Frankfurt am Main 60528 Frankfurt am Main, Germany

doi:10.1016/j.ajem.2010.01.025

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