Clinical determinants of fever in clozapine users and implications for treatment management: A narrative review

Hélène Verdoux, Clélia Quiles, Jose de Leon

Research output: Contribution to journalReview articlepeer-review

24 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)1-9
Number of pages9
JournalSchizophrenia Research
Volume211
DOIs
StatePublished - Sep 2019

Bibliographical note

Funding 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.

Funding Information:
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.

Publisher Copyright:
© 2019 Elsevier B.V.

Keywords

  • Adverse drug reaction
  • Clozapine
  • Fever
  • Infection
  • Inflammation

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Biological Psychiatry

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