Clozapine and cardiotoxicity – A guide for psychiatrists written by cardiologists

Patel, Rishi; Moore, Alice; Piper, Susan; Sweeney, Mark; Whiskey, Eromona; Cole, Graham; Shergill, Sukhi; Plymen, Carla M.

doi:10.1016/j.psychres.2019.112491

Cited by 35 publications

(37 citation statements)

References 43 publications

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“…A recent systematic review and meta-analysis study reported that the significant event rates of CLZ-induced adverse drug reactions between Australia and outside of Australia were 2% and 0.3%, respectively [ 43 ]. These discrepancies among registries are likely caused by the lack of clear diagnostic criteria for CLZ-induced cardiotoxicity [ 44 ]. Although guidelines were proposed, these are not in line with current cardiac practice, and have a significant risk of either under- or over-diagnosis [ 44 ].…”

Section: Adverse Drug Reactions Of Clzmentioning

confidence: 99%

“…These discrepancies among registries are likely caused by the lack of clear diagnostic criteria for CLZ-induced cardiotoxicity [ 44 ]. Although guidelines were proposed, these are not in line with current cardiac practice, and have a significant risk of either under- or over-diagnosis [ 44 ].…”

Section: Adverse Drug Reactions Of Clzmentioning

confidence: 99%

“…An electrocardiogram (ECG) is not recommended for the diagnosis of myocarditis [ 44 , 47 , 51 ], as ECG results are typically normal; however, it is not uncommon to display sinus tachycardia, nonspecific abnormalities, or specific abnormality similar to acute myocardial infarction [ 44 , 47 ]. Troponin has guideline-based measurements for the identification of coronary ischaemia and inflammation as an established cardiac-specific biomarker, whereas creatine kinase and c-reactive protein are not used to diagnose myocarditis due to their insufficient specificity and sensitivity [ 49 , 50 ].…”

Section: Adverse Drug Reactions Of Clzmentioning

confidence: 99%

“…ECG does not comprise diagnostic criteria for cardiomyopathy, but can indicate important information regarding the aetiology (Q waves seen in myocardial infarction, left ventricular hypertrophy and strain seen in hypertension, etc.) and potential therapy (QRS duration when considering the implantation of cardiac resynchronisation therapy devices) [ 44 ]. There is no specific biomarker of cardiomyopathy associated with CLZ, but elevation of the brain natriuretic peptide or N-terminal pro brain natriuretic peptide, which suggest the possibility of the existence of active myocarditis or cardiomyopathy [ 53 ], are guideline-based blood tests for access to specialist care [ 44 ].…”

Section: Adverse Drug Reactions Of Clzmentioning

confidence: 99%

See 3 more Smart Citations

A Working Hypothesis Regarding Identical Pathomechanisms between Clinical Efficacy and Adverse Reaction of Clozapine via the Activation of Connexin43

Okada

Fukuyama

Shiroyama

et al. 2020

IJMS

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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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Section: Adverse Drug Reactions Of Clzmentioning

confidence: 99%

Section: Adverse Drug Reactions Of Clzmentioning

confidence: 99%

Section: Adverse Drug Reactions Of Clzmentioning

confidence: 99%

Section: Adverse Drug Reactions Of Clzmentioning

confidence: 99%

See 2 more Smart Citations

A Working Hypothesis Regarding Identical Pathomechanisms between Clinical Efficacy and Adverse Reaction of Clozapine via the Activation of Connexin43

Okada

Fukuyama

Shiroyama

et al. 2020

IJMS

View full text Add to dashboard Cite

show abstract

“…Besides other CVSEs discussed, there is one life-threatening, early myocarditis and later cardiomyopathy. The potential mechanism of clozapine-induced cardiotoxicity could be explained by oxidative stress, decreased parasympathetic tone and increased adrenergic tone, immunoglobulins or cytokines responses or through the direct toxic effects on myocardial tissue 64 . It might occur in the first 2-8 weeks of treatment or later, unpredictable, dose-independent and it could be reversible when early treatment is discontinued and supportive therapy is used 65 .…”

Section: Myocarditis and Cardiomyopathymentioning

confidence: 99%

Cardiovascular side effects of neuropsychiatric medication: an update

APETREI-CORDUNEANU¹,

Fildan²,

Radu³

et al. 2020

Arch Balk Med Union

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Schizophrenia and Related Psychoses

2021

The Maudsley Prescribing Guidelines in Psychiatry

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Despite disagreements about nomenclature, patients who develop schizophrenic or schizophrenialike symptoms in later life are often seen in clinical practice. Questions about the etiology of late-life psychotic disorders and about their similarities or differences from early-onset disorders remain unanswered. Neuroimaging techniques have been used to study patients with late onset of psychosis, and in substantial subgroups of patients (from 25% to 100% in various studies) compared with agematched control subjects, structural and functional abnormalities have been found. We review the literature on imaging in late-life schizophrenia and related psychotic disorders, and we present data from our own investigations of patients with these disorders. We discuss the potential usefulness of imaging evaluations in patients with late-onset disorders, and we offer suggestions for future investigations.

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Clozapine and cardiotoxicity – A guide for psychiatrists written by cardiologists

Cited by 35 publications

References 43 publications

A Working Hypothesis Regarding Identical Pathomechanisms between Clinical Efficacy and Adverse Reaction of Clozapine via the Activation of Connexin43

A Working Hypothesis Regarding Identical Pathomechanisms between Clinical Efficacy and Adverse Reaction of Clozapine via the Activation of Connexin43

Cardiovascular side effects of neuropsychiatric medication: an update

Schizophrenia and Related Psychoses

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