Isolated nausea and vomiting as the cardinal presenting symptoms of clozapine-induced myocarditis: a case report

Horst, Marte Z van der; Houwelingen, F. Van; Luykx, Jurjen J.

doi:10.1186/s12888-020-02955-9

Cited by 7 publications

(4 citation statements)

References 35 publications

(48 reference statements)

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“…304,305 Cardiac side effects CIM is among the most important and yet underdiagnosed side effects. CIM risk is the highest during the first 4 weeks after treatment initiation, 306,157 but also during re-exposure following a first successful trial. 94 Moreover, rare cases of CIM after long-term treatment of more than a decade have also been observed.…”

Section: Therapeutic Advances In Psychopharmacologymentioning

confidence: 99%

Second to none: rationale, timing, and clinical management of clozapine use in schizophrenia

Qubad

Bittner

2023

Therapeutic Advances in Psychopharmacology

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Despite its enduring relevance as the single most effective and important evidence-based treatment for schizophrenia, underutilization of clozapine remains considerable. To a substantial degree, this is attributable to a reluctance of psychiatrists to offer clozapine due to its relatively large side-effect burden and the complexity of its use. This underscores the necessity for continued education regarding both the vital nature and the intricacies of clozapine treatment. This narrative review summarizes all clinically relevant areas of evidence, which support clozapine’s wide-ranging superior efficacy – for treatment-resistant schizophrenia (TRS) and beyond – and make its safe use eminently feasible. Converging evidence indicates that TRS constitutes a distinct albeit heterogeneous subgroup of schizophrenias primarily responsive to clozapine. Most importantly, the predominantly early onset of treatment resistance and the considerable decline in response rates associated with its delayed initiation make clozapine an essential treatment option throughout the course of illness, beginning with the first psychotic episode. To maximize patients’ benefits, systematic early recognition efforts based on stringent use of TRS criteria, a timely offer of clozapine, thorough side-effect screening and management as well as consistent use of therapeutic drug monitoring and established augmentation strategies for suboptimal responders are crucial. To minimize permanent all-cause discontinuation, re-challenges after neutropenia or myocarditis should be considered. Owing to clozapine’s unique efficacy, comorbid conditions including substance use and most somatic disorders should not dissuade but rather encourage clinicians to consider clozapine. Moreover, treatment decisions need to be informed by the late onset of clozapine’s full effects, which for reduced suicidality and mortality rates may not even be readily apparent. Overall, the singular extent of its efficacy combined with the high level of patient satisfaction continues to distinguish clozapine from all other available antipsychotics.

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Section: Therapeutic Advances In Psychopharmacologymentioning

confidence: 99%

Second to none: rationale, timing, and clinical management of clozapine use in schizophrenia

Qubad

Bittner

2023

Therapeutic Advances in Psychopharmacology

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“…Myocarditis ranks among the most relevant and consequential clozapine-associated side-effects [54,55]. Compared to clozapine-induced agranulocytosis and neutropenia, incidence rates of CIM are higher with estimates ranging between 0.03 and 8.5 % [55][56][57].…”

Section: Epidemiologymentioning

confidence: 99%

“…Compared to clozapine-induced agranulocytosis and neutropenia, incidence rates of CIM are higher with estimates ranging between 0.03 and 8.5 % [55][56][57]. The risk for CIM is highest during the first two months after treatment initiation [58][59][60][61] with mortality rates in undetected cases ranging from 10-30 % [54,55]. Importantly, there have also been reports of a delayed onset of CIM after longterm treatment [62][63][64] as well as during re-exposure following a first successful trial [56].…”

Section: Epidemiologymentioning

confidence: 99%

When, Why and How to Re-challenge Clozapine following Myocarditis

Qubad¹,

Dupont²,

Hahn³

et al. 2023

Preprint

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Clozapine-induced myocarditis (CIM) is among the most important side-effects limiting the use of clozapine as the most effective treatment for schizophrenia and schizoaffective disorder. CIM necessitates immediate termination of clozapine, often resulting in its permanent discontinuation with considerable detrimental effects on patient’s psychopathology and long-term outcome. Consequently, a clozapine re-challenge after CIM has been discussed, with published reports indicating a success rate of approximately 60 %. However, compared to re-challenges after clozapine-induced neutropenia for CIM cases remain considerably more limited. Here, we provide a narrative review of the current state of research regarding the epidemiology, pathophysiology, risk factors, diagnosis, and clinical management of CIM. Moreover, we review current recommendations for re-challenging patients after CIM. We illustrate these issues using a case presentation with a special focus on the relevance of CRP, troponin, NT-proBNP, therapeutic drug-monitoring and cardiac MRI. Our review and case presentation underscore the importance of swiftly attempting to reinitiate clozapine after CIM given the lack of effective alternatives. Cardiac MRI might aid this strategy due to its high sensitivity for detecting myocardial inflammation. Moreover, both previous findings and our case indicate that using slow dose titration regimes and addressing other risk factors for CIM including concomitant valproate are crucial to ensure a safe and successful re-challenge.

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“…7 Clozapine-induced myocarditis is a potentially lifethreatening condition and reported mortality rates range from 10% to 30%. 9 While the mechanism for clozapineinduced myocarditis is not fully understood, it appears that an immunoglobulin E-mediated hypersensitivity reaction is the predominating driver. 10 Animal models demonstrate disruption to multiple physiological processes, including upregulation of pro-inflammatory and cholinergic agents, increased myocardial apoptosis, oxidative stress and the concurrent downregulation of endogenous antioxidants.…”

Section: Introductionmentioning

confidence: 99%

Risk factors for clozapine‐induced myocarditis and cardiomyopathy: A systematic review and meta‐analysis

Vickers

Ramineni

Malacova

et al. 2022

Acta Psychiatr Scand

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Objective: Clozapine is the most effective medication for treatment-refractory schizophrenia, but it is associated with severe cardiac adverse events including myocarditis and cardiomyopathy. To aid treatment decision-making for clinicians, patients and their carers, we conducted a systematic review and metaanalysis to identify potential risk factors for clozapine-induced myocarditis and cardiomyopathy.Methods: A systematic search was conducted of PubMed, Embase, CINAHL, Web of Science, Cochrane and PsycInfo for studies reporting myocarditis and cardiomyopathy among people on clozapine and potential risk factors. We calculated pooled effect sizes on risk factors using a random-effects meta-analytic model. Risk of publication bias was assessed using the Newcastle-Ottawa scale.Results: Seven studies met the inclusion criteria, of which six studies had quantitative data included in the meta-analysis. The odds of clozapine-induced myocarditis increased with concurrent sodium valproate use (k = 6, n = 903, pooled OR 3.58, 95% CI 1.81-7.06), but were not significantly greater with the use of quetiapine, lithium or selective serotonin reuptake inhibitors. Our qualitative review identified conflicting results reported for increasing age and higher clozapine dose as risk factors for myocarditis. No other factors, including genetic risk, sex, ethnicity, smoking, alcohol, substance abuse or cardiometabolic disease, were associated with greater odds of myocarditis. No risk factors for cardiomyopathy were identified in the literature. Conclusion: Concurrent use of sodium valproate increases the odds of clozapineinduced myocarditis. Thus, clinicians should consider the temporary cessation of sodium valproate during the initial titration phase of clozapine.

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Isolated nausea and vomiting as the cardinal presenting symptoms of clozapine-induced myocarditis: a case report

Cited by 7 publications

References 35 publications

Second to none: rationale, timing, and clinical management of clozapine use in schizophrenia

Second to none: rationale, timing, and clinical management of clozapine use in schizophrenia

When, Why and How to Re-challenge Clozapine following Myocarditis

Risk factors for clozapine‐induced myocarditis and cardiomyopathy: A systematic review and meta‐analysis

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