Quetiapine and Elevated Creatine Phosphokinase (CK)

There is only one report of severe rhabdomyolysis associated with quetiapine overdose and one report of a possible association [3] [5]. Only few reports about the serious consequences following quetiapine overdose exist [1] [4] [6]. Here, we report a case of suspected rhabdomyolysis following quetiapine overdose.

A 29-year-old man with schizophrenia was admitted to the hospital after overdosing with quetiapine. He reported ingestion of 12,000 mg of quetiapine with no other drugs, as later also confirmed by his mother, and then slept for 32 hours. After waking up he had severe pain, tenderness and weakness in the muscles of his lower extremities, and could walk only with sticks. On examination nine hours after awakening, he still had the same symptoms, with bruising on the thighs, with no other pathological and/or neurological signs; he was conscious and alert but felt tired and also worried about his condition. His blood pressure was 125/85 mm Hg, heart rate was 88 beats/min, body temperature and ECG were normal. The QTc interval was 433 msec, his chest X-ray was normal and no obvious signs for infectious diseases were present. Laboratory tests at admission revealed severe elevation of creatine phosphokinase to 13353 U/L (normal values up to 170 U/L), elevation of lactate dehydrogenase to 570 U/L (normal values up to 247 U/L), aspartate aminotransferase to180 U/L and alanine aminotransferase to 66 U/L. Sodium was 137 mmol/L, potassium 4.5 mmol/L, creatinine 1.3 mg/dL, C-reactive protein 138 mg/L and WBC 22.5×10⁹/L; other laboratory values were within normal ranges. Urine screens for illicit drugs and blood alcohol level were negative. Urine or serum myoglobin tests could not be performed because of technical difficulties.

After 12 hours of extensive hydration with saline solution, creatine phosphokinase decreased to 6646 U/L and lactate dehydrogenase to 353 U/L. Aspartate aminotransferase was 179 U/L, alanine aminotransferase 70 U/L, C-reactive protein 127 mg/L, sodium 134 mmol/L, potassium 3.89 mmol/L, WBC 16.08×10⁹/L, and the urine myoglobin test was negative. Quetiapine serum concentration was 0.03 mg/L, 53 hours after ingestion, at the end of hydration. The patient was discharged after 10 days with the diagnosis of probable rhabdomyolysis, with no pathological sequelae and with all laboratory values within normal ranges.

The most common causes of rhabdomyolysis are alcohol abuse, muscle exertion, muscle compression, the use of certain medications or illicit drugs and causes may also be of traumatic, heat-related, ischemic, infectious, inflammatory, metabolic and endocrinological origin. In our case we could not determine whether the rhabdomyolysis was due to the direct toxicity of the quetiapine overdose or was a consequence of immobilization during sleep. It could be also connected with an infectious cause because of the elevated level of WBC and C-reactive protein even with no obvious symptoms of infectious disease. There is one report of diffuse muscle pain with quetiapine in therapeutic dosage [2]. We should consider a risk of rhabdomyolysis with quetiapine, especially in overdose, and be proactive if there is a patient complaining about muscle pain during therapy with quetiapine.

References

• 1 Harmon TJ, Benitez JG, Krenzelok EP. Loss of consciousness from acute quetiapine overdosage.  J Toxicol Clin Toxicol. 1998;  36 599-602
• 2 Fountoulakis KN, Iacovides A, Kaprinis SG, Kaprinis GS. Diffuse muscle pain with quetiapine.  Br J Psychiat. 2003;  182 81
• 3 Himmerich H, Ehrlinger M, Hackenberg M, Lohr B, Nickel T. Possible case of quetiapine-induced rhabdomyolysis in a patient with depression treated with fluoxetine.  J Clin Psychopharmacol. 2006;  26 676-677
• 4 Pollack PT, Zbuk K. Quetiapine fumarate overdose: clinical and pharmacological lessons from extreme conditions.  Clin Pharmacol Ther. 2000;  68 92-97
• 5 Smith R, Puckett BN, Crawford J, Elliott RL. Quetiapine overdose and severe rhabdomyolysis.  J Clin Psychopharmacol. 2004;  24 343
• 6 Fernandes PP, Marcil WA. Death associated with quetiapine overdose.  Am J Psychiat. 2002;  159 2114

Correspondence