Neuroleptic malignant syndrome associated with long-term clozapine treatment: report of a case and results of a clozapine rechallenge.

Clozapine has recently been found to be associated with neuroleptic malignant syndrome (NMS) after long-term treatment. Here, I report on a 34-year-old Taiwanese woman who had been diagnosed with schizophrenic disorder 17 years previously. She had received clozapine 250 mg/day monotherapy for 7 years. She had sudden onset of NMS signs with high fever, profuse diaphoresis, severe muscular rigidity, elevated creatine phosphokinase level and consciousness disturbance. Brain computed tomography, blood culture and cerebral spinal fluid studies were negative. She had no muscle rigidity and fever after treatment with normal saline 1500 ml/day and diazepam 30 mg/day for 8 days. On day 15, a rechallenge with clozapine was done with caution because the patient was experiencing auditory hallucinations and delusions of persecution. The dose was slowly increased to 250 mg/day over 18 days. She had no active psychotic symptoms or NMS again in the following year. I reported this case to remind readers of the possibility of induced NMS with long-term use of clozapine and successful clozapine rechallenge.