Role of cytokine changes in clozapine‐induced fever: A cohort prospective study

Hung, Yuan‐Pin; Wang, Carol Sheei‐Meei; Yen, Chia‐Nan; Chang, Hsun‐Cheng; Chen, Po See; Lee, I Hui; Chen, Kao Chin; Yang, Yen Kuang; Lu, Ru‐Band; Wang, Tzu Yun

doi:10.1111/pcn.12508

Cited by 25 publications

(26 citation statements)

References 33 publications

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“…For instance, nine patients with diagnosed schizophrenia or schizoaffective disorder, who were treated with clozapine 100-400 mg/day, showed increased risk of developing fever after the first intake, and IL-6 might play a specific role in the interaction effect between treatment duration and fever development (94,95). Clozapine has also been shown to increase soluble IL-2 receptor (sIL-2R) and IL-6 levels (96,97). Similarly, the adipokine resistin was associated with several acute and chronic inflammatory states and promoted the expression of TNF-α and IL-6 by human mononuclear cells (97) (see Table 2).…”

Section: Clozapinementioning

confidence: 99%

Immunoendocrine Peripheral Effects Induced by Atypical Antipsychotics

et al. 2020

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Atypical antipsychotics (AAP) or second-generation antipsychotics are the clinical option for schizophrenia treatment during acute psychoses, but they are also indicated for maintenance during lifetime, even though they are being used for other psychiatric conditions in clinical practice such as affective disorders and autism spectrum disorder, among others. These drugs are differentiated from typical antipsychotics based on their clinical profile and are a better choice because they cause fewer side effects regarding extrapyramidal symptoms (EPS). Even though they provide clear therapeutic benefits, AAP induce peripheral effects that trigger phenotypic, functional, and systemic changes outside the Central Nervous System (CNS). Metabolic disease is frequently associated with AAP and significantly impacts the patient's quality of life. However, other peripheral changes of clinical relevance are present during AAP treatment, such as alterations in the immune and endocrine systems as well as the intestinal microbiome. These less studied alterations also have a significant impact in the patient's health status. This manuscript aims to revise the peripheral immunological, endocrine, and intestinal microbiome changes induced by AAP consumption recommended in the clinical guidelines for schizophrenia and other psychiatric disorders.

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Section: Clozapinementioning

confidence: 99%

Immunoendocrine Peripheral Effects Induced by Atypical Antipsychotics

et al. 2020

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“…Even in the absence of frank NMS, some antipsychotics have been noted to cause fever, with clozapine being the most notable. In reference to clozapine, fever is most commonly seen within the first 3 weeks of therapy, and has a very wide reported incidence (0.5-55%) [26,30,31]. While clozapine-induced fevers are generally noted to be transient (lasting between 2 and 4 days on average) and benign, they may necessitate discontinuation, or at the very least further investigation to rule out alternative pathophysiology [26,27,32].…”

Section: Literature Reviewmentioning

confidence: 99%

“…In the instance where clozapine is restarted after discontinuation, case reports determine it is well-tolerated with no further episodes of fever; however, Chung et al found 1 out of 7 patients (14.3%) had fever on rechallenge [28,33]. It is unclear if fever from clozapine is related to dose or the rate of titration, though it has been noted to occur with titration rates of > 50 mg/week, and when given concomitantly with valproic acid [28,31]. Studies have demonstrated that the pro-inflammatory cytokine interleukin-6 may have a specific role in mediating clozapine-induced fevers [31].…”

Section: Literature Reviewmentioning

confidence: 99%

A case report of acute hypothermia during initial inpatient clozapine titration with review of current literature on clozapine-induced temperature dysregulations

2020

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Background: Here we describe a unique case of clozapine-associated hypothermia during initial titration of this medication in an acute inpatient psychiatry setting. Only a handful of cases on this topic have been published. We discuss possible pharmacologic mechanisms supporting or refuting the propensity of clozapine to induce hypothermia, as well as risk factors for clozapine-induced hypothermia, and a comparison to clozapine-induced hyperthermia. Case presentation: A 70 year-old African American female with treatment-refractory schizoaffective disorder developed hypothermia with a nadir temperature of 89°F (31.7°C) after 7 days on clozapine, on a total dose of 50 mg twice daily. Accompanying symptoms included bradycardia, hypotension, QTc prolongation, tachypnea, hypoxemia, and an absence of shivering. The patient was transferred to the ICU, and rewarmed within 10 h with the discontinuation of her clozapine, ziprasidone, and carvedilol. Broad spectrum antibiotics were initiated, but discontinued shortly after, as the patient had no leukocytosis, and blood cultures were negative. Discussion: While hypoglycemia, hypothyroidism, sepsis, and stroke were effectively ruled out, alternative drugdisease (including chronic kidney disease), and drug-drug interactions were considered possible contributing features. Benzodiazepines, valproic acid, ziprasidone, and the numerous antihypertensive agents the patient was taking were considered as either primary or compounding factors for hypothermia. After exclusion or inclusion of these alternative causes, we calculated a score of 4 (possible) for clozapine-induced hypothermia on the Naranjo Scale. Conclusions: Clozapine-induced hypothermia may occur more commonly than clinicians believe. Practitioners should be cognizant of this potentially fatal phenomenon, and monitor for temperature dysregulations while on clozapine, especially during initial titration, in those with multiple comorbid factors, and on additional medications that may contribute to hypothermia.

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“…Clinical response and the presence of adverse events vary among individuals taking clozapine. Although the molecular mechanisms of clozapine action are still unclear (Yamamori et al, 2013 , 2014 ; Hung et al, 2017 ; Kinoshita et al, 2017 ; Lee et al, 2017 ; Nakazawa et al, 2017 ), twin studies suggest that genetic factors may contribute to the variance in therapeutic and adverse effects of clozapine (Vojvoda et al, 1996 ; Horácek et al, 2001 ; Theisen et al, 2001 ; Wehmeier et al, 2005 ; Anil Yagcioglu et al, 2011 ).…”

Section: Introductionmentioning

confidence: 99%

Clozapine Pharmacogenetic Studies in Schizophrenia: Efficacy and Agranulocytosis

et al. 2018

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Clozapine is an efficacious atypical antipsychotic for treatment-refractory schizophrenia. Clinical response and appearance of adverse events vary among individual patients receiving clozapine, with genetic and non-genetic factors potentially contributing to individual variabilities. Pharmacogenetic studies investigate associations between genetic variants and drug efficacy and toxicity. To date, most pharmacogenetic studies of clozapine have been conducted through candidate gene approaches. A recent advance in technology made it possible to perform comprehensive genetic mapping underlying clinical phenotypes and outcomes, which allow novel findings beyond biological hypotheses based on current knowledge. In this paper, we will summarize the studies on clozapine pharmacogenetics that have extensively examined clinical response and agranulocytosis. While there is still limited evidence on clozapine efficacy, recent genome-wide studies provide further evidence of the involvement of the human leukocyte antigen (HLA) region in clozapine-induced agranulocytosis.

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Role of cytokine changes in clozapine‐induced fever: A cohort prospective study

Abstract: Patients who were treated with clozapine for the first time have an increased rate of developing a fever, and IL-6 might have a specific role in the interaction effect between treatment duration and fever development.

Cited by 25 publications

References 33 publications

Immunoendocrine Peripheral Effects Induced by Atypical Antipsychotics

Immunoendocrine Peripheral Effects Induced by Atypical Antipsychotics

A case report of acute hypothermia during initial inpatient clozapine titration with review of current literature on clozapine-induced temperature dysregulations

Clozapine Pharmacogenetic Studies in Schizophrenia: Efficacy and Agranulocytosis

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