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Polygenic overlap with granulocyte counts identifies novel loci for clozapine metabolism and clozapine-induced agranulocytosis.
Neuropsychopharmacology
January 2025
Centre for Precision Psychiatry, Division of Mental Health and Addiction, Oslo University Hospital, and Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
While clozapine is the most effective antipsychotic drug, its use is limited due to hematological adverse effects involving the reduction of granulocyte counts with potential life-threatening agranulocytosis. It is not yet possible to predict or prevent the risk of agranulocytosis, and the mechanisms are unknown but likely related to clozapine metabolism. Genome-wide association studies (GWASs) of clozapine metabolism and clozapine-induced agranulocytosis have identified few genetic loci.
View Article and Find Full Text PDFClozapine Induces Agranulocytosis via Inflammatory and Hematopoietic Cytokine Induction of the JAK-STAT Signaling Pathway: Evidence From Network Pharmacology and Molecular Docking.
CNS Neurosci Ther
January 2025
Computational Biology Center, Tianjin Anding Hospital, Nankai University Affiliated Tianjin Anding Hospital, Tianjin Mental Health Center of Tianjin Medical University, Tianjin, China.
Background: Clozapine exhibits significant therapeutic efficacy in schizophrenia, especially treatment-resistant schizophrenia. However, clozapine can cause agranulocytosis, a fatal adverse effect, and the aim of this study is to explore this mechanism based on network pharmacology and molecular docking.
Method: Six and two databases were used to identify targets associated with clozapine and agranulocytosis, respectively.
Network pharmacology and molecular docking to explore mechanisms of clozapine-induced cardiac arrest.
J Psychiatry Neurosci
January 2025
From the Computational Biology Centre and the Laboratory of Psychiatric-Neuroimaging-Genetic and Comorbidity, Tianjin Anding Hospital, Tianjin Mental Health Centre of Tianjin Medical University, Nankai University Affiliated Tianjin Anding Hospital, Tianjin, China.
Background: Clozapine is superior to all other antipsychotics in treating schizophrenia in terms of its curative efficacy; however, this drug is prescribed only as a last resort in the treatment of schizophrenia, given its potential to induce cardiac arrest. The mechanism of clozapine-induced cardiac arrest remains unclear, so we aimed to elucidate the potential mechanisms of clozapine-induced cardiac arrest using network pharmacology and molecular docking.
Methods: We identified and analyzed the overlap between potential cardiac arrest-related target genes and clozapine target genes.
Clozapine-Associated Sialorrhea: A Literature Review.
J Clin Psychopharmacol
October 2024
TOBB University of Economics and Technology, Faculty of Medicine, Ankara, Turkey.
Background: Clozapine has demonstrated efficacy in treating treatment-resistant schizophrenia; however, it has a wide range of side effects. Sialorrhea is a common side effect of clozapine that causes the patient to withdraw from social life. This review aims to evaluate and summarize the prevalence, mechanism, risk factors, and management of clozapine-associated sialorrhea.
View Article and Find Full Text PDFClozapine rechallenge following myocarditis: a systematic review of rechallenge cases.
CNS Spectr
December 2024
Faculty of Medicine, University of Queensland, Brisbane, QLD, Australia.
Introduction And Objectives: Clozapine is the antipsychotic medication with the greatest efficacy in treatment-resistant schizophrenia (TRS). Unfortunately, clozapine is ceased in approximately 0.2% to 8.
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