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A 22-year-old, white, nonsmoking man was admitted to the psychiatric ward with symptoms of psychosis. In the previous year he had been experiencing auditory hallucinations. At the time of admission, he endorsed tactile hallucinations, somatic delusions and delusions of reference. He had been using marijuana daily and inhaling solvents frequently. He underwent a thorough psychiatric evaluation, including an electroencephalogram (EEG) and head computed tomography. Initially there was insufficient information to differentiate between schizo phrenia and drug-induced psychosis; however, with time and sobriety, the diagnosis of schizophrenia became clear. The patient was started on risperi-done, but severe extrapyramidal symptoms developed. He then underwent trials of olanzapine and aripriprazole, but was unable to tolerate these owing to extrapyramidal symptoms and poor control of psychotic symptoms, respectively. A family meeting was held to discuss clozapine. The risks, side effects and benefits of the medication were explained, and the decision was made to initiate a trial. He was started at 12.5 mg daily and titrated to 100 mg twice daily over 10 days. On day 14, a fever of 39.1°C developed. The on-call psychiatrist stopped the clozapine, but the treating psychiatrist restarted it at a low dose (25 mg twice daily) the next day. A thorough medical workup was completed; his blood counts, blood cultures , urine culture, troponins, creatine kinase and chest radiograph were all normal. The patient felt unwell, and his blood indicated dehydration and elevated creatinine. The patient tolerated the clozapine well, and was at a dose of 100 mg twice daily 10 days later, with good control of his psychotic symptoms. Clozapine and norcloza-pine levels at this dose were 1764 and 990, respectively. The fever persisted for 5 days after the initial spike and then dissipated along with his systemic symptoms. The highest recorded temperature was 40.1°C. This case illustrates a difficult clinical decision when fever appears during clozapine treatment: continue cloza-pine while determining the source of the fever, as in this case, or stop cloza-pine while completing the workup and, if appropriate, rechallenge. Because fever is also an early sign of neuro leptic malignant syndrome, myo-carditis or infection in the presence of agranulocytosis, all rare but potentially fatal side effects of clozapine, the latter choice is often made. However, this choice also creates the potential for emergent symptoms, a prolonged hospital stay and a rechallenge of reduced efficacy. As fever is also a common and benign side effect of …

Management of clozapine-induced fever: a case of continued therapy throughout fever