Successful rechallenge with clozapine following ‘red alert’

Toni-Uebari, Thelma K; Rees, J. K. H.

doi:10.1136/bcr-2012-007172

Cited by 5 publications

(3 citation statements)

References 10 publications

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“…Rather, present data are based on case series and indicate a re-challenge after CIM to be a reasonable approach if important prerequisites have been met [57,88,109,116,[123][124][125][126][127][128]. These include a detailed risk-benefit assessment, an appropriate hospital setting ensuring frequent cardiological consultations and especially the patient's full recovery from a previous CIM [125].…”

Section: Background Re-challengementioning

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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Section: Background Re-challengementioning

confidence: 99%

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

Qubad¹,

Dupont²,

Hahn³

et al. 2023

Preprint

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“…At present, there are no established consensus guidelines for re-challenges after CIM, but rather protocols based on case series. 243 , 309 , 315 , 407 , 410 , 427 – 431 Importantly, a re-challenge should only be attempted after patients have made a full recovery from CIM. 427 It requires intensive clinical, laboratory and electrophysiological (ECG, TTE) monitoring (e.g.…”

Section: Discontinuation and Re-challenge Of Clozapinementioning

confidence: 99%

“…Presently, there are no established consensus guidelines for re-challenges after CIM, but rather protocols based on case series 179,189,195,294,297,[316][317][318][319][320] . Importantly, a rechallenge should only be attempted after patients have made a full recovery from CIM 316 .…”

Section: Re-challenge After Myocarditismentioning

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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