Fatal neuroleptic malignant syndrome in a previously long-term user of clozapine following its reintroduction in combination with paroxetine

A 77-year-old patient with initial behavioral and psychological symptoms of dementia was treated with clozapine (50 mg/daily). Since no clinical benefit was apparent, clozapine was discontinued after six weeks and the patient started on paroxetine (20 mg/daily). After three weeks on paroxetine, he was given another trial of clozapine at a starting dosage of 25 mg/daily. While clozapine had previously been well tolerated, this time he rapidly developed fever, mental confusion, lethargy, muscle spasms and rigidity. The diagnosis of neuroleptic malignant syndrome was delayed, because there was no leukocytosis and serum creatine phosphokinase was initially not elevated. Subcutaneous apomorphine was then given but, after an initial improvement, the patient developed a multiple organ failure syndrome and died.