Do proinflammatory cytokines play a role in clozapine-associated glycometabolism disorders?

Zhao, Tuanjie; Zhang, Kai; Zhang, Yelei; Yang, Yating; Ning, Xiaoshuai; Hu, Yu; Li, Xiaoyue; Xia, Lei; Ren, Zhenhua; Liu, Huanzhong

doi:10.1007/s00213-021-05824-9

Cited by 12 publications

(8 citation statements)

References 59 publications

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“…It has been suggested that clozapine can have an effect on serum IL-6 levels in patients with schizophrenia [14,16,40], so we also explored the relationship between clozapine and serum IL-6 levels in the TRS group. Nevertheless, our results were based on a relatively small sample size, which needs to be verified in further studies with large samples.…”

Section: Discussionmentioning

confidence: 99%

“…In vitro, the second-generation atypical antipsychotics olanzapine and aripiprazole showed an effect on the reduction in IL-6 concentrations of primary human peripheral blood mononuclear cells (PBMC) from healthy individuals [13]. In addition, it has been noted that elevated IL-6 levels in schizophrenia may contribute to the occurrence of metabolic syndrome [14][15][16]. However, metabolic syndrome is one of the most common side effects of second-generation atypical antipsychotics.…”

Section: Introductionmentioning

confidence: 99%

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Sex differences in the association of treatment-resistant schizophrenia and serum interleukin-6 levels

Wei

et al. 2023

Preprint

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Background Low-grade inflammation and altered inflammatory markers have been observed in treatment-resistant schizophrenia (TRS). Interleukin-6 (IL-6) is one of the proinflammatory cytokines linked with TRS and receives increasing attention. Previous studies showed that patients with TRS might have higher IL-6 levels compared with healthy individuals and treatment-responsive patients. Besides, emerging evidence has suggested that there are sex differences in the associations between IL-6 levels and various illnesses, including chronic hepatitis C, metabolic syndrome, etc.; however, there is limited study on TRS. In this present study, we aimed to compare the serum IL6 levels of TRS and partially responsive schizophrenia (PRS) and explore potential sex differences in the association of TRS and IL-6 levels. Methods The study population consisted of a total of 90 patients with schizophrenia: 64 TRS patients (45.3% males and 54.7% females) and 26 PRS patients (46.2% males and 53.8% females). We measured serum IL-6 levels using enzyme-linked immunosorbent assay (ELISA) and analyzed them separately by sex, controlling for confounders (age, education, medication, body mass index, and PANSS scores) rigorously. Result The results showed that IL-6 levels increased significantly in the TRS group compared with the PRS group (p = 0.005), and a positive correlation tendency was observed between IL-6 levels and PANSS total scores (r = 0.27, p = 0.070) in all the females. In males, there were no differences in IL-6 levels between the TRS and PRS (p = 0.124). Conclusion Our findings provided evidence supporting the hypothesis that the inflammatory response system (IRS) may play a role in the pathogenesis of TRS in a sex-dependent manner. In addition, sex differences in the immune dysfunction of individuals with schizophrenia cannot be neglected, and inflammation in male and female TRS should be discussed separately.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Sex differences in the association of treatment-resistant schizophrenia and serum interleukin-6 levels

Wei

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…In vitro, the second-generation atypical antipsychotics olanzapine and aripiprazole showed an effect on the reduction in IL-6 concentrations of primary human peripheral blood mononuclear cells (PBMC) from healthy individuals [ 13 ]. In addition, it has been noted that elevated IL-6 levels in schizophrenia may contribute to the occurrence of metabolic syndrome [ 14 – 16 ]. However, metabolic syndrome is one of the most common side effects of second-generation atypical antipsychotics.…”

Section: Introductionmentioning

confidence: 99%

“…However, metabolic syndrome is one of the most common side effects of second-generation atypical antipsychotics. Besides, it has been observed that clozapine increases IL-6 expression in murine pancreatic tissue [ 16 ]. So, the effect of antipsychotics on IL-6 levels seems to be controversial, which also suggests that different types of antipsychotics may have different impacts on IL-6.…”

Section: Introductionmentioning

confidence: 99%

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Sex differences in the association of treatment-resistant schizophrenia and serum interleukin-6 levels

Wei

et al. 2023

BMC Psychiatry

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Background Low-grade inflammation and altered inflammatory markers have been observed in treatment-resistant schizophrenia (TRS). Interleukin-6 (IL-6) is one of the pro-inflammatory cytokines linked with TRS and receives increasing attention. Previous studies showed that patients with TRS might have higher IL-6 levels compared with healthy individuals and treatment-responsive patients. Besides, emerging evidence has suggested that there are sex differences in the associations between IL-6 levels and various illnesses, including chronic hepatitis C, metabolic syndrome, etc.; however, there is limited study on TRS. In this present study, we aimed to compare the serum IL-6 levels of TRS and partially responsive schizophrenia (PRS) and explore potential sex differences in the association of TRS and IL-6 levels. Methods The study population consisted of a total of 90 patients with schizophrenia: 64 TRS patients (45.3% males and 54.7% females) and 26 PRS patients (46.2% males and 53.8% females). We measured serum IL-6 levels using enzyme-linked immunosorbent assay (ELISA) and analyzed them separately by gender, controlling for confounders (age, education, medication, body mass index, and PANSS scores) rigorously. Result The results showed that patients with TRS had higher serum IL-6 levels than patients with PRS (p = 0.002). In females, IL-6 levels increased significantly in the TRS group compared with the PRS group (p = 0.005). And a positive correlation tendency was observed between IL-6 levels and PANSS general sub-scores (r = 0.31, p = 0.039), although this correlation was not significant after correcting for multiple comparisons. Whereas, there were no differences in IL-6 levels between the TRS and PRS (p = 0.124) in males. Conclusion Our findings provided evidence supporting the hypothesis that the inflammatory response system (IRS) may play a role in the pathogenesis of TRS in a sex-dependent manner. In addition, sex differences in the immune dysfunction of individuals with schizophrenia cannot be neglected, and inflammation in male and female TRS should be discussed separately.

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Analysis of clinical studies on clozapine from 2012-2022

Freibüchler,

Seifert

2024

Naunyn-Schmiedeberg's Arch Pharmacol

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Clozapine has been considered the “gold standard” in the treatment of schizophrenia for many years. Clozapine has a superior effect, particularly in the treatment of negative symptoms and suicidal behaviour. However, due to its numerous adverse reactions, clozapine is mainly used for treatment-resistant schizophrenia. The aim of this paper is to analyze the results of clinical studies on clozapine from 2012-2022. PubMed was used as the database. Sixty-four studies were included and categorised by topic. The pharmacokinetic properties of clozapine tablets and a clozapine suspension solution did not differ markedly. Clozapine was superior to olanzapine and risperidone in reducing aggression and depression. A long-term study showed that metabolic parameters changed comparably with olanzapine and clozapine after 8 years. Risperidone and ziprasidone can be used as an alternative to clozapine. Scopolamine, atropine drops, and metoclopramide are effective in the treatment of clozapine-induced hypersalivation. Eight drugs, including liraglutide, exenatide, metformin, and orlistat, are potentially effective in the treatment of clozapine-induced weight gain. Ziprasidone, haloperidol, and aripiprazole showed a positive effect on symptoms when added to clozapine. No investigated drug was superior to clozapine for the treatment of schizophrenia. Ziprasidone and risperidone can also be used well for the treatment of schizophrenia. In the treatment of clozapine-induced hypersalivation and weight gain, some drugs proved to be effective.

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Do proinflammatory cytokines play a role in clozapine-associated glycometabolism disorders?

Cited by 12 publications

References 59 publications

Sex differences in the association of treatment-resistant schizophrenia and serum interleukin-6 levels

Sex differences in the association of treatment-resistant schizophrenia and serum interleukin-6 levels

Sex differences in the association of treatment-resistant schizophrenia and serum interleukin-6 levels

Analysis of clinical studies on clozapine from 2012-2022

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