Protocol for Clozapine Rechallenge in a Case of Clozapine-Induced Myocarditis

Shivakumar, Geetha; Thomas, Naveen; Sollychin, Miranda; Takács, Anna; Kolamunna, S; Melgar, P.; Connally, Fiona; Neil, Christopher; Bousman, Chad A.; Jayaram, Mahesh; Pantelis, Christos

doi:10.1177/0706743719892709

Cited by 17 publications

(19 citation statements)

References 20 publications

(26 reference statements)

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“…Exploring previous case reports describing instances of clozapine rechallenge, Manu and colleagues found that while rechallenge was a rational option for patients with neutropenia or neuroleptic malignant syndrome, it carried major risks for patients with agranulocytosis or myocarditis 27 . Still, there are a few reports of clozapine‐induced myocarditis in which clozapine was successfully resumed (after temporary discontinuation) by increasing the dosage more cautiously while measuring CRP and troponin levels in close coordination with cardiologists 28–30 …”

Section: Discussionmentioning

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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Section: Discussionmentioning

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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“…In fact, many of the case reports included in this review described marked improvements in patient symptoms and functioning prior to the development of myocarditis that could not be sustained following clozapine discontinuation. However, guidelines for performing a clozapine rechallenge in this clinical context have not been developed, although protocols have been proposed (Shivakumar et al, 2019). Our review sought to identify potential clinical factors associated with successful clozapine rechallenge to inform future guideline development.…”

Section: Discussionmentioning

confidence: 99%

Clozapine-induced myocarditis and patient outcomes after drug rechallenge following myocarditis: a systematic case review

Richardson

Greenway

Bousman

2021

Preprint

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Clozapine is underutilized due, in part, to concerns about rare but severe adverse drug reactions, including cardiac inflammation and injury (myocarditis). Risk factors for clozapine induced myocarditis are limited and predictors for the successful rechallenge of clozapine after an episode of myocarditis are even more poorly understood. We conducted a systematic review, in accordance with the PRISMA recommendation, of published case reports to describe demographic and clinical characteristics of patients with clozapine induced myocarditis and identify potential markers of clozapine rechallenge success. A total of 180 cases from 88 articles were evaluated. Male cases of clozapine associated myocarditis were more frequently reported than female cases by a ratio of 6:1. Less than half of patients reported the presence of chest pain (35%) or flu like symptoms (43%) but increases in troponin or C-reactive protein were present in 87% of cases. Clozapine rechallenge was carried out in 34 (2 female) cases, with successful reintroduction in 22 (2 female) cases (64.7%). Only chest pain during the initial trial was found to be significantly associated with rechallenge success (odds ratio = 6.87, 95% CI = 1.17, 40.3). Standardized reporting of clozapine induced myocarditis cases is needed to facilitate the identification of factors associated with successful rechallenge.

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“…Treatment with diuretics, angiotensin converting enzyme inhibitors, beta-blockers and steroids might be needed [ 13 ]. In general, future rechallenge of clozapine is not recommended due to the high risk of recurrence of cardiac problems [ 32 , 33 ]. However, due to the lack of an equally effective alternative antipsychotic, sometimes rechallenge is embarked, after carefully weighing the benefits and risks.…”

Section: Discussionmentioning

confidence: 99%

“…However, due to the lack of an equally effective alternative antipsychotic, sometimes rechallenge is embarked, after carefully weighing the benefits and risks. Shivakumar et al (2019) proposed a protocol for clozapine rechallenge in which they suggest a strategy of slow titration combined with interruption of titration once any indices increase (monocytes, neutrophils, eosinophils, or CRP) [ 32 ].…”

Section: Discussionmentioning

confidence: 99%

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

2020

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Background Clozapine is an atypical antipsychotic proven to be superior in the treatment of treatment-resistant schizophrenia. Myocarditis is a rare, but well-known complication of treatment with clozapine. Only few cases have been reported in which nausea and vomiting were prominent symptoms. This is the first described report in which nausea and vomiting were the only presenting symptoms of clozapine-induced myocarditis. Case presentation We report a case of a 58-year-old woman, suffering from schizoaffective disorder, who is being treated with clozapine. Two weeks after initiation of clozapine, she developed nausea and vomiting, in absence of any other clinical symptoms. Laboratory examination and magnetic resonance imaging confirmed the diagnosis of clozapine-induced myocarditis. Clozapine was discontinued and the patient recovered fully. Conclusions This case emphasizes the importance of recognizing myocarditis as a cause of isolated nausea and vomiting in patients treated with clozapine. Early recognition improves clinical outcome and reduces mortality.

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Protocol for Clozapine Rechallenge in a Case of Clozapine-Induced Myocarditis

Cited by 17 publications

References 20 publications

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

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

Clozapine-induced myocarditis and patient outcomes after drug rechallenge following myocarditis: a systematic case review

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

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