Incidence and risk factors for clozapine-induced myocarditis and cardiomyopathy at a regional mental health service in Australia

Youssef, Daniel; Narayanan, Pradeep; Gill, Neeraj

doi:10.1177/1039856215604480

Cited by 46 publications

(61 citation statements)

References 17 publications

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“…According to a large observational study, cardiomyopathy may occur as well with CLO, potentially leading to heart failure 114. Echocardiography is the gold standard procedure to detect and monitor cardiomyopathy.…”

Section: Methodsmentioning

confidence: 99%

Safety, tolerability, and risks associated with first- and second-generation antipsychotics: a state-of-the-art clinical review

Solmi

Murru

Pacchiarotti

et al. 2017

TCRM

337

244

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Since the discovery of chlorpromazine (CPZ) in 1952, first-generation antipsychotics (FGAs) have revolutionized psychiatric care in terms of facilitating discharge from hospital and enabling large numbers of patients with severe mental illness (SMI) to be treated in the community. Second-generation antipsychotics (SGAs) ushered in a progressive shift from the paternalistic management of SMI symptoms to a patient-centered approach, which emphasized targets important to patients – psychosocial functioning, quality of life, and recovery. These drugs are no longer limited to specific Diagnostic and Statistical Manual of Mental Disorders (DSM) categories. Evidence indicates that SGAs show an improved safety and tolerability profile compared with FGAs. The incidence of treatment-emergent extrapyramidal side effects is lower, and there is less impairment of cognitive function and treatment-related negative symptoms. However, treatment with SGAs has been associated with a wide range of untoward effects, among which treatment-emergent weight gain and metabolic abnormalities are of notable concern. The present clinical review aims to summarize the safety and tolerability profile of selected FGAs and SGAs and to link treatment-related adverse effects to the pharmacodynamic profile of each drug. Evidence, predominantly derived from systematic reviews, meta-analyses, and clinical trials of the drugs amisulpride, aripiprazole, asenapine, brexpiprazole, cariprazine, clozapine, iloperidone, lurasidone, olanzapine, paliperidone, quetiapine, risperidone, sertindole, ziprasidone, CPZ, haloperidol, loxapine, and perphenazine, is summarized. In addition, the safety and tolerability profiles of antipsychotics are discussed in the context of the “behavioral toxicity” conceptual framework, which considers the longitudinal course and the clinical and therapeutic consequences of treatment-emergent side effects. In SMI, SGAs with safer metabolic profiles should ideally be prescribed first. However, alongside with safety, efficacy should also be considered on a patient-tailored basis.

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Section: Methodsmentioning

confidence: 99%

Safety, tolerability, and risks associated with first- and second-generation antipsychotics: a state-of-the-art clinical review

Solmi

Murru

Pacchiarotti

et al. 2017

TCRM

337

244

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show abstract

“…Because myocarditis can progress quickly to cardiomyopathy and congestive heart failure, the best management strategy is to monitor for it, so that it can be recognized quickly. Slow titration may help. At a minimum, patients initiating clozapine should be monitored weekly for signs and symptoms of myocarditis, including chest pain, dyspnea, orthopnea, peripheral edema, palpitations, fatigue, flu‐like symptoms including fever, nausea and vomiting, and diaphoresis.…”

Section: Specific Adverse Effectsmentioning

confidence: 99%

Management of common adverse effects of antipsychotic medications

2018

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The benefits of antipsychotic medications are sometimes obscured by their adverse effects. These effects range from relatively minor tolerability issues (e.g., mild sedation or dry mouth) to very unpleasant (e.g., constipation, akathisia, sexual dysfunction) to painful (e.g., acute dystonias) to disfiguring (e.g., weight gain, tardive dyskinesia) to life-threatening (e.g., myocarditis, agranulocytosis). Importantly, adverse effect profiles are specific to each antipsychotic medication and do not neatly fit into first- and second-generation classifications. This paper reviews management strategies for the most frequent side effects and identifies common principles intended to optimize net antipsychotic benefits. Only use antipsychotics if the indication is clear; only continue antipsychotics if a benefit is discernible. If an antipsychotic is providing substantial benefit, and the adverse effect is not life-threatening, then the first management choice is to lower the dose or adjust the dosing schedule. The next option is to change the antipsychotic; this is often reasonable unless the risk of relapse is high. In some instances, behavioral interventions can be tried. Finally, concomitant medications, though generally not desirable, are necessary in many instances and can provide considerable relief. Among concomitant medication strategies, anticholinergic medications for dystonias and parkinsonism are often effective; beta-blockers and anticholinergic medications are useful for akathisia; and metformin may lead to slight to moderate weight loss. Anticholinergic drops applied sublingually reduce sialorrhea. Usual medications are effective for constipation or dyslipidemias. The clinical utility of recently approved treatments for tardive dyskinesia, valbenazine and deutetrabenazine, is unclear.

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“…Indeed, 50% of CLZ-induced asymptomatic myocarditis were described as fatal [ 47 , 48 ]. Rapid dose titration during the early exposure stage, concomitant with valproate and selective serotonin reuptake inhibitor (SSRI) of CLZ, increased the risk of development of myocarditis [ 49 , 50 ].…”

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%

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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Incidence and risk factors for clozapine-induced myocarditis and cardiomyopathy at a regional mental health service in Australia

Abstract: These results illustrate a high incidence of clozapine-induced myocarditis as well as cardiomyopathy, reinforcing the need for a standardised, mandatory monitoring scheme. Concomitant SSRI use as one such potential predictor merits further study.

Cited by 46 publications

References 17 publications

Safety, tolerability, and risks associated with first- and second-generation antipsychotics: a state-of-the-art clinical review

Safety, tolerability, and risks associated with first- and second-generation antipsychotics: a state-of-the-art clinical review

Management of common adverse effects of antipsychotic medications

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

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