Fever, rigidity and confusion in a 28-year-old man

A 28-year-old man was admitted to the psychiatric inpatient unit with a four-day history of worsening agitation and paranoid delusions. He had a background history of major depressive disorder, for which he had been taking fluoxetine 20 mg once daily for the past six months. On admission, his general practitioner had also prescribed haloperidol 5 mg twice daily and lorazepam 1 mg twice daily as required for agitation. Over the next two weeks, his agitation settled, but on day 14 he became acutely unwell. He was noted to be confused and disoriented, with a temperature of 38.9°C, profuse sweating, and severe generalised muscle rigidity. He was unable to speak coherently and was incontinent of urine. His blood pressure was labile, ranging from 200/110 mmHg to 90/50 mmHg, and his heart rate was 130 beats per minute. Laboratory investigations on the same day showed a creatine kinase of 12,000 U/L, a white blood cell count of 15.0 × 10^9/L, and a serum creatinine of 120 μmol/L (baseline 80 μmol/L). Blood cultures, urine cultures, and a chest X-ray were unremarkable. A computed tomography scan of the head showed no acute abnormality. The on-call team considered a diagnosis of sepsis; however, the absence of a focus of infection and negative cultures made this unlikely. Serotonin syndrome was also considered because of the concurrent use of fluoxetine, but the marked rigidity and the very high creatine kinase were more consistent with neuroleptic malignant syndrome. Haloperidol and lorazepam were discontinued on day 15. Fluoxetine was continued. After withdrawal of haloperidol, the patient's temperature settled within 24 hours, and his rigidity improved gradually over 48 hours. He required supportive care in the intensive care unit for four days. His creatine kinase had fallen to 3,000 U/L by day 17 and returned to normal by day 21. His cognitive function improved more slowly, and he was discharged from the psychiatric unit after a further two weeks. He was not rechallenged with haloperidol because of the risk.