Objectives: To identify the clinical determinants of fever in clozapine users and their impact on management of clozapine treatment. Methods: Articles published in English or French identified with a MEDLINE, Web of Sciences, Cochrane Library and PsycINFO search, from inception through February 2019, using the term “clozapine” in combination with “fever” OR “hyperthermia” OR “body temperature” OR “pyrexia” OR “febrile” OR “heat” OR “thermoregulation”. Information extracted for each medical condition were frequency, time to onset after initiation of clozapine treatment, characteristics of fever, associated symptoms, laboratory tests used for diagnosis, course, lethality, discontinuation of clozapine. Data were synthesized narratively. Results: Our search yielded 394 unique hits published from 1993 to 2018. We included 73 articles in the review: two meta-analyses, 14 reviews, six epidemiological studies, 11 clinical studies and 40 case reports. During clozapine initiation, fever is most frequently benign and transient but should be closely monitored as it may be the first stage of potentially life-threatening adverse drug reactions (ADR) (agranulocytosis, neuroleptic malignant syndrome myocarditis, hepatitis, pancreatitis, nephritis, colitis, etc.). Other ADR associated with fever are independent of duration of exposure to clozapine (heat stroke, pneumonia, pulmonary embolism, necrotizing colitis). If fever is due to intercurrent infection, therapeutic drug monitoring is recommended to adjust clozapine daily dosage. Conclusion: Benign causes of fever are much more frequent than life-threatening ADR during clozapine treatment. Discontinuation should not be considered as automatic in the event of fever, especially during the early phase of clozapine initiation.
|Number of pages||9|
|State||Published - Sep 2019|
Bibliographical noteFunding Information:
This is an independent study funded by the autonomous resources of INSERM (Institut National de la Santé et de la Recherche Médicale), Bordeaux Population Health Research Center, team pharmacoepidemiology, UMR 1219.
This is an independent study funded by the autonomous resources of INSERM (Institut National de la Sant? et de la Recherche M?dicale), Bordeaux Population Health Research Center, team pharmacoepidemiology, UMR 1219. The authors thank Ray Cooke for copyediting the manuscript.
© 2019 Elsevier B.V.
- Adverse drug reaction
ASJC Scopus subject areas
- Psychiatry and Mental health
- Biological Psychiatry