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Increases in C-Reactive Protein May Predict Recurrence of Clozapine-Induced Fever

Staff Psychiatrist, Geriatric Psychiatry Division, North Shore–Long Island Jewish Health System, The Zucker Hillside Hospital, Glen Oaks, NY; Assistant Professor of Psychiatry and Behavioral Sciences, Albert Einstein College of Medicine, Bronx, NY

Noman Afzal, MD

Psychiatry Extern, North Shore – Long Island Jewish Health System, The Zucker Hillside Hospital

Saira Hussain, MD

Psychiatry Resident, North Shore – Long Island Jewish Health System, The Zucker Hillside Hospital

Peter Manu, MD

Director of Medical Services, North Shore – Long Island Jewish Health System, The Zucker Hillside Hospital

Reprints: Dr. Kohen, Ambulatory Care Pavilion – Room 2106, Geriatric Psychiatry Division, North Shore – Long Island Jewish Health System, 75-59 263rd St., Glen Oaks, NY 11004, fax 718/962-7712, ikohen{at}nshs.edu

OBJECTIVE: To report a case of recurrent clozapine-induced fever that was associated with a rise in C-reactive protein (CRP).

CASE SUMMARY: A 73-year-old man with Lewy Body dementia was admitted for psychosis. He was treated with clozapine (initial dose 12.5 mg/day, titrated to 75 mg/day over 15 days). On day 15 of clozapine therapy, he developed a benign fever (maximum 38.4 °C) that was associated with a rise in the CRP level (3.96 mg/dL). The level normalized when clozapine was discontinued. However, when the patient was rechallenged with clozapine, the CRP level became elevated (4.36 mg/dL) after 3 days of therapy, with a subsequent recurrence of fever (38.7 °C).

DISCUSSION: We postulate that the elevation in CRP levels and the subsequent fever were caused by the effects of clozapine on the cytokine system via interleukin-6 and tumor necrosis factor-, resulting in an inflammatory response with an acute phase reaction. This case is unique, as it is the first reported in the literature associating a recurrence of clozapine-induced fever with the known immunomodulatory effects of clozapine on cytokines and CRP level. According to the Naranjo probability scale, this adverse effect is probably associated with clozapine.

CONCLUSIONS: Clozapine-related fever is generally benign but difficult to assess and manage, as it can be confused with much more serious conditions. Further research is needed to study whether CRP is a useful tool in predicting and managing clozapine fever.

Key Words: clozapine, C-reactive protein, immunomodulatory

Published Online, January 6, 2009. www.theannals.com, DOI 10.1345/aph.1L467