Key result
Pharmacodynamic review of clozapine cardiotoxicity and severe adverse reactions proposes amended patient monitoring strategies.
Why the study?
Severe clozapine-associated adverse reactions such as pneumonia, cardiotoxicity, and seizures show greater prevalence and relative lethality than agranulocytosis, requiring an amended monitoring system.
This review highlights the need to amend clozapine monitoring systems to address severe adverse reactions like pneumonia, cardiotoxicity, and seizures, proposing a pathomechanism involving Connexin43.
May warrant revised clozapine monitoring for pneumonia, cardiotoxicity, and seizures; leaves open Connexin43-targeted strategies pending prospective validation.
Clozapine (CLZ) is an approved antipsychotic agent for the medication of treatment-resistant schizophrenia but is also well known as one of the most toxic antipsychotics. Recently, the World Health Organization's (WHO) global database (VigiBase) reported the relative lethality of severe adverse reactions of CLZ. Agranulocytosis is the most famous adverse CLZ reaction but is of lesser lethality compared with the other adverse drug reactions of CLZ. Unexpectedly, VigiBase indicated that the prevalence and relative lethality of pneumonia, cardiotoxicity, and seizures associated with CLZ were more serious than that of agranulocytosis. Therefore, haematological monitoring in CLZ patients monitoring system provided success in the prevention of lethal adverse events from CLZ-induced agranulocytosis. Hereafter, psychiatrists must amend the CLZ patients monitoring system to protect patients with treatment-resistant schizophrenia from severe adverse CLZ reactions, such as pneumonia, cardiotoxicity, and seizures, according to the clinical evidence and pathophysiology. In this review, we discuss the mechanisms of clinical efficacy and the adverse reactions of CLZ based on the accumulating pharmacodynamic findings of CLZ, including tripartite synaptic transmission, and we propose suggestions for amending the monitoring and medication of adverse CLZ reactions associated with pneumonia, cardiotoxicity, and seizures.
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Okada et al. (2020) conducted a review in Treatment-resistant schizophrenia. Clozapine was evaluated. Clozapine efficacy and severe adverse reactions, including pneumonia, cardiotoxicity, and seizures, are discussed based on pharmacodynamic findings to propose amended patient monitoring strategies.
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