Successful Clozapine Re-Challenge After Suspected Clozapine-Induced Myocarditis

Hosseini, Seyed Alireza; Skrzypcak, Brianna; Yasaei, Rama; Abdijadid, Sara; Joolhar, Fowrooz; Win, Theingi Tiffany; Moosavi, Leila

doi:10.12659/ajcr.926507

Cited by 9 publications

(7 citation statements)

References 28 publications

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“…Rather, the singular status of clozapine underscores the importance to seriously consider a re-challenge even after severe side effects. This notion is supported by a growing body of evidence for a positive risk-benefit ratio and considerable success rates for clozapine re-challenges after neutropenia 151,283 , neuroleptic malignant syndrome 294 and to a lesser extent myocarditis 169,295,296 . Any re-challenge must only be attempted in an appropriate hospital setting with sufficient support by relevant specialists, i.e.…”

Section: Managing Discontinuationmentioning

confidence: 93%

“…This notion is supported by a growing body of evidence for a positive risk–benefit ratio and considerable success rates for clozapine re-challenges after neutropenia, 217 , 395 NMS, 407 and to a lesser extent myocarditis. 224 , 408 , 409 Any re-challenge must only be attempted in an appropriate hospital setting with sufficient support by relevant specialists, that is, cardiologists or hematologists. 224 , 410 …”

Section: Discontinuation and Re-challenge Of Clozapinementioning

confidence: 99%

“…every second to third day) and very slow dose titration (e.g. 12.5–25 mg per week), 243 , 408 – 410 , 427 , 432 which reduces CIM recidivism risk. 315 , 427 Re-challenge success rates after CIM are currently estimated at approximately 60%, 431 but with a high degree of uncertainty.…”

Section: Discontinuation and Re-challenge Of Clozapinementioning

confidence: 99%

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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: Managing Discontinuationmentioning

confidence: 93%

Section: Discontinuation and Re-challenge Of Clozapinementioning

confidence: 99%

See 1 more Smart Citation

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

Qubad

Bittner

2023

Therapeutic Advances in Psychopharmacology

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show abstract

Section: Managing Discontinuationmentioning

confidence: 94%

Second to None – Rationale, Timing, and Clinical Management of Clozapine Use in Schizophrenia

Qubad¹,

Bittner²

2022

Preprint

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Despite its continued relevance as the single most effective and important evidence-based treatment for schizophrenia, the degree of underutilization of clozapine across health systems remains considerable. To a substantial degree, this is attributable to a reluctance of psychiatrists to use clozapine due to its relatively large side-effect burden and its comparatively complex dosing and monitoring requirements. This underscores the necessity for continued education of clinicians in the intricacies of clozapine use and in the still growing case in favor of this vital treatment option. Consequently, this narrative review provides a comprehensive outline of all lines of evidence, which support clozapine’s wide-ranging superior efficacy, and of the current knowledge regarding the prevalence and diagnosis of treatment resistance. The distinct neurobiological and clinical characteristics of this condition makes the swift initiation of clozapine indispensable. Moreover, we review the extensive literature regarding clozapine’s side effect profile and current recommendations for optimal treatment and monitoring algorithms including for particularly vulnerable populations such as elderly patients and pregnant women and for potential re-challenges after myocarditis and neutropenia. We also discuss established approaches to increase treatment response as well as augmentation strategies for patients with partial or full clozapine resistance. We argue for a clear focus on early and consistent detection and management of side effects, which can ensure patient safety and reduce permanent all-cause discontinuation. This strategy needs to be combined with a long-term approach acknowledging the late onset of clozapine’s full advantageous effects, which – in cases like reduced mortality rates – even then may not be easily discernible. Our aim is to encourage a safer, more frequent, and timely use of clozapine to maximize patients’ short- and long-term benefits. Even now, the extent of these benefits as well as patient’s satisfaction with treatment still clearly set clozapine apart from all other available treatment options.

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“…Consent to the rechallenge of clozapine was obtained from the patient and a guardian after a shared decision‐making process considering the benefits and risks of the treatment. When planning, we referenced a case report in which a patient was successfully rechallenged with clozapine after experiencing clozapine‐induced myocarditis 3 . From a starting dose of 12.5 mg on Day 81, we carefully incremented the dose by 25 mg/week, which was slower than the standard protocol.…”

Section: Case Presentationmentioning

confidence: 99%

Successful rechallenge with clozapine after discontinuation due to drug‐induced pneumonia: A case report

Kikuchi¹,

Komatsu

Sakuma

et al. 2022

PCN Reports

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Background: There have been a limited number of case reports of clozapine-induced pneumonia. Few have reported rechallenging of clozapine after discontinuation due to the side-effect.Case Presentation: A 43-year-old man was diagnosed with schizophrenia after developing auditory hallucinations and delusions of persecution and reference. After diagnosing him with treatment-resistant schizophrenia, clozapine was started. From a starting dose of 12.5 mg/day, we increased it by 25 mg every 2-3 days to reach 150 mg/day by Day 15. On Day 17, his body temperature suddenly rose to 39.6°C (103.3°F) without any other apparent physical symptoms. Blood biochemistry testing showed elevated C-reactive protein (CRP) and high counts of leukocytes and neutrophils, but not eosinophils. Chest computed tomography revealed ground-glass opacities in the lower lobes of both lungs. Suspecting bacterial pneumonia, we started him on levofloxacin 500 mg/day. However, pneumonia exacerbated, and eosinophilia became apparent 5 days after the onset of fever. We suspected acute eosinophilic pneumonia induced by clozapine and discontinued its administration the same day. The patient clinically recovered the next day after stopping clozapine. After stopping clozapine, his psychiatric symptoms, such as persecutory/referential delusions, irritability, and polydipsia, became worse. We decided to rechallenge with clozapine in incremental doses slower than the standard protocol, along with careful monitoring of CRP and eosinophil counts. Pneumonia has not recurred, and his psychiatric symptoms have been well managed. Conclusion:Our experience suggests that some patients with inflammatory reactions to clozapine can still take the drug if it is reintroduced with caution.

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Successful Clozapine Re-Challenge After Suspected Clozapine-Induced Myocarditis

Cited by 9 publications

References 28 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

Second to None – Rationale, Timing, and Clinical Management of Clozapine Use in Schizophrenia

Successful rechallenge with clozapine after discontinuation due to drug‐induced pneumonia: A case report

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