Hélène Verdoux1, Clélia Quiles2, Jose de Leon3. 1. Univ. Bordeaux, Inserm, Bordeaux Population Health Research Center, Team Pharmacoepidemiology, UMR 1219, F-33000 Bordeaux, France; Centre Hospitalier Charles Perrens, F-33000 Bordeaux, France. Electronic address: helene.verdoux@u-bordeaux.fr. 2. Centre Hospitalier Charles Perrens, F-33000 Bordeaux, France. 3. Mental Health Research Center at Eastern State Hospital, Lexington, KY and Psychiatry and Neurosciences Research Group (CTS-549), USA; Institute of Neurosciences, University of Granada, Granada, Spain; Biomedical Research Centre in Mental Health Net (CIBERSAM), Santiago Apostol Hospital, University of the Basque Country, Vitoria, Spain.
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.
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.
Authors: H Javelot; P-M Llorca; D Drapier; E Fakra; C Hingray; G Meyer; S Dizet; A Egron; C Straczek; M Roser; M Masson; R Gaillard; P Fossati; E Haffen Journal: Encephale Date: 2020-05-04 Impact factor: 1.291
Authors: H Javelot; C Straczek; G Meyer; C Gitahy Falcao Faria; L Weiner; D Drapier; E Fakra; P Fossati; S Weibel; S Dizet; B Langrée; M Masson; R Gaillard; M Leboyer; P M Llorca; C Hingray; E Haffen; A Yrondi Journal: Encephale Date: 2021-09-02 Impact factor: 1.291
Authors: Jose de Leon; Can-Jun Ruan; Georgios Schoretsanitis; Christopher Rohde; Elif Anıl Yağcıoğlu; Trino Baptista; Oleg O Kirilochev; Carlos De Las Cuevas; Christoph U Correll Journal: Gen Psychiatr Date: 2022-06-29
Authors: Jose de Leon; Can-Jun Ruan; Georgios Schoretsanitis; Carlos De Las Cuevas Journal: Psychother Psychosom Date: 2020-04-14 Impact factor: 17.659