A case of clozapine intoxication presenting with atypical NMS symptoms

Abstract

Clozapine is an antipsychotic drug indicated for treatment-resistant schizophrenia. Clozapine at toxic doses may cause hyperthermia, alterations in consciousness, seizures, cardiac arrhythmias, excessive mucus production in bronchi, hypersalivation, miosis, blood dyscrasias, pancreatitis and hepatitis (Sartorius et al., 2002). Clozapine blood levels are influenced by age, gender, ethnicity, physical illnesses like liver failure, changes in the activity of the cytochrome oxidase enzymes due to genetic variability, concurrent medication use, smoking or caffeine consumption (Greenwood-Smith et al., 2003). Generally, plasma levels of over 1000 ng/ml are associated with central nervous system adverse effects (Varma et al., 2011). One potentially lethal side effect of antipsychotics including clozapine is neuroleptic malignant syndrome (NMS). Neuroleptic malignant syndrome is typically characterized by fever, altered mental status, leukocytosis, autonomic dysfunction and rigidity. Atypical antipsychotics including clozapine are associated less with NMS than typical antipsychotics, and when NMS occurs during treatment with atypical antipsychotics, associated symptoms are less typical (Trollor et al., 2012). In this case report, we present a patient using clozapine for treatment of schizophrenia who was admitted to the Emergency Room with NMS-like symptoms. We present a 53 yr old, female patient diagnosed with schizophrenia, who was on clozapine 500 mg/d for the past 3 yr. She had hyperlipidemia and chronic obstructive pulmonary disease (COPD) and was using rosuvastatin 20 mg/d. She was admitted to the Emergency Room (ER) with acute onset-confusion, shivering, meaningless talk and urinary incontinence. Her body temperature was 39.2°C, blood pressure 90/50 mmHg, pulse rate 117/min, RR: 17/min, SaO2:%96. Electrocardiogram (ECG) was normal. Her Glasgow Coma Score was 15. Blood tests showed hyponatremia (133.2 mEq/l), increased levels of creatinine (1.52 mg/dl), BUN (23.68 mg/dl), uric acid (7.07 mg/dl) and decreased levels of phosphorus (2.50 mg/dl). Liver and thyroid function tests and potassium, chloride and calcium levels were within normal range. Complete …