Clozapine-induced myocarditis: separating the wheat from the chaff (original) (raw)
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A systematic review of clozapine-induced myocarditis
International Journal of Cardiology, 2018
Background: Clozapine is an atypical antipsychotic that is beneficial to some patients who failed to have an adequate clinical response to other antipsychotic drugs. Its clinical use is limited due to several potentially fatal adverse reactions including myocarditis. Careful monitoring of patients on clozapine is required. Methods: We conducted a systematic review of the literature on myocarditis associated with clozapine therapy. The search engines used to identify cases were MEDLINE, EMBASE, PsycINFO and Cochrane reviews. The references included in the manuscripts reviewed were searched to identify additional reports. Results: We identified a total of 3347 articles that addressed the cardiac complications of clozapine. Of these, 82 articles detailed cases of clozapine-induced myocarditis. The median age of patients and dose of clozapine at presentation was 30 years and 250 mg/day respectively. Symptoms and signs of myocarditis developed in 87% of patients within the first month of treatment. Clinical presentation included: shortness of breath (67%), fever (67%) and tachycardia (58%). Cardiac markers were elevated in 87% of the 54 cases that reported these markers. Global ventricular dysfunction was the predominant echocardiogram finding (57%). Conclusions: Patients on clozapine require routine monitoring for symptoms and signs of myocarditis during the first three months of therapy. This adverse drug reaction is difficult to diagnose due the non-specific nature of the symptoms and signs. Alternate causes of myocarditis should be ruled out before attributing the myocarditis to clozapine.
Schizophrenia Research, 2011
Background: Fatal clozapine-induced myocarditis has not been investigated systematically. We describe the clinical course of 10 fatal cases of myocarditis with clozapine and identify factors associated with fatality. Methods: Cases of myocarditis were documented from the patient's medical records and fatal cases also from autopsy reports. Results: The fatal cases of myocarditis occurred 1996-2009 and were diagnosed at autopsy. Before death, three had no symptoms of illness and only three had cardiac-specific diagnostic results. None was investigated by cardiac imaging techniques, and in none was myocarditis suspected before death. Duration of clozapine for the fatal cases was 14-33 days with an outlier at 4.5 months. Only 3 cases had significant coronary artery disease at autopsy. Comparison of these ten cases with 66 non-fatal cases indicated no significant difference in gender, age, smoking status, dose at onset or concomitant sodium valproate. However, obesity (BMI N 30 kg/m 2 ) was significantly more frequent among fatal than non-fatal cases (60% vs 26%; p b 0.03) and duration of clozapine was significantly longer for fatal cases (20.8 vs 17.0 days; p b 0.006), after exclusion of one outlier. Creatine kinase (CK) N 1000 U/L was also associated with death (p = 0.0004). Conclusions: Routine monitoring for myocarditis for the first 4 weeks of clozapine, and discontinuation of clozapine in the presence of evidence consistent with myocarditis may assist to prevent fatalities occurring from early-onset myocarditis. Investigation by cardiac imaging will give a measure of severity and need for intervention. Obesity may increase the risk of mortality and CK N 1000 U/L may indicate life-threatening illness.
Clozapine-Associated Myocarditis
Drug Safety, 2007
suicide rate compared with other antipsychotic agents. Clozapine is used specifically in patients for whom previous therapy was inadequate or not tolerated, and is the only antipsychotic agent associated with the development of myocarditis. Objective: To retrospectively review all adverse drug reaction reports voluntarily submitted to the Australian Adverse Drug Reactions Unit mentioning suspected myocarditis in clozapine-treated patients. Patients and methods: We accessed all electronic database entries and case reports citing suspected myocarditis associated with clozapine therapy from January 1993 through to December 2003, inclusive. Results: 116 case reports of suspected myocarditis amongst clozapine-treated patients were identified during the specified time frame (incidence between 0.7% and 1.2% of treated patients). Median patient age for these cases was 30 years (SD 11.1 years) compared with 37 years from the Clopine registry. The condition developed within a median 16 days (mean 19.8 days; SD 17.3 days) of commencing clozapine for the bulk of patients developing myocarditis within 6 months (n = 93, 80.2%). For all cases with known treatment commencement and cessation dates (n = 106), the condition developed within a median 17 days (mean 171.7 days, SD 530.9 days). Over nine-tenths of cases were prescribed clozapine within the dose range of 100 mg/day to 450 mg/day. Sixty patients (51.8%) recovered from their episode when reported or during follow-up reports, whereas 17 patients (14.7%) had not yet recovered: 27 patients (23.3%) had unknown outcome when reported and the remaining 12 patients (10.3%) died. Conclusion: Clozapine is uncommonly but importantly related to myocarditis, often fatal or near fatal and sometimes in relatively young patients with early onset after treatment initiation. The most striking feature about this condition is 48 Haas et al.
Clozapine Induced Myocarditis: a case report
Indian Journal of Mental Health 2023; 10(1), 2024
Clozapine is commonly used in resistant schizophrenia, but its use has been limited because of side effects. Myocarditis is one of the rare and potentially fatal side effects that can occur at any time after initiation of treatment but typically occurs within 2 to 3 weeks after initiation treatment with clozapine. We report the case of a 28-year-old patient who developed myocarditis after initiation treatment with clozapine, and a successful re-challenge of starting Clozapine. The physician should be cautious during the initiation of rapid clozapine titration early in treatment and follow the guidelines of close monitoring with laboratory investigation. This allows the early detection of myocarditis and reduces the risk of fatal mortality.
Clozapine-induced myocarditis: Two case reports and review of clinical presentation and recognition
Mental Health Clinician, 2018
Myocarditis is a potentially fatal cardiac disease marked by inflammation of the heart muscle. With a noted black-box warning, rates of clozapine-induced myocarditis are reportedly as high as 3%. Since the first case of clozapine-induced myocarditis was documented in 1994, more than 250 cases have been described in literature with an approximate 33% case-fatality rate. We report 2 cases of patients with primary psychotic disorders treated with clozapine, who developed signs and symptoms of myocarditis. The first was a 35-year-old white male patient with a primary diagnosis of schizoaffective disorder (bipolar type) who was initiated on clozapine after nonresponse to several therapies. On day 26, the patient was admitted to the emergency department for chest pain presenting with eosinophilia and notable elevations in several biomarkers, including troponin and C-reactive protein. The second patient was a 45-year-old black male who was initiated on clozapine for treatment-resistant sch...
A Case of Suspected Clozapine Related Myocarditis
The atypical neuroleptic clozapine is known to have considerable advantages over typical neuroleptics in the treatment of Schizophrenia. It has been used successfully to treat children and adults. However, generally psychiatrists resort to it only after trying many other antipsychotics. This presentation will include a case report of a 37-year-old Chinese man who developed palpitations, headache, and fever of sudden onset. An illustration of the subsequent clinical features and laboratory investigation will be given. Increased usage in the future may be brought about by enhanced knowledge on the early signs and symptoms of cardiac related side effects, stringent monitoring for cardiac related side effects and a deeper understanding of its pathophysiology.
Myocarditis after administration of Clozapine
OBJECTIVE: Clozapine is an atypical antpsychotic medication with established efficacy in patients diagnosed of resistant schizophrenia. However, clozapine has multiple side effects. Cardiac complications such as myocarditis and cardiomyopathy have always been related with treatment with clozapine. METHODS: A 42 year old Caucasian male, with history of schizophrenia developed a acute myocarditis after commencement of clozapine. RESULTS: : The patient recovered with intensive medical support. The symptoms occurred approximately 20 days after starting clozapine. CONCLUSIONS: Myocarditis is an ingreasingly recognized complication associated with clozapine. Use of clozapine must be based on a balance of its risks and benefits on an individual basis which for the most part defines its use in treatment refractory schizophrenia. Appropriate monitoring of adverse events is an essential part of the clinical usage of clozapine and should be charted for at least two years.
2016
Myocarditis occurs more frequently during clozapine (CLZ) administration than during treatment with other antipsychotic drugs (APs). In this observational study, we transversally screened outpatients for myocarditis by comparing a CLZ group of 132 subjects, with a non-CLZ group taking other APs (n = 371) only, and in 21 CLZ-treated patients and 18 subjects treated with other APs who had been followed for more than one year. The protocol included a) assessment of symptoms such as dyspnea, tachycardia, chest discomfort, fever, cough, and edema, b) blood pressure and heart auscultation; c) a standard electrocardiogram after a 5-minute rest, d) white cell count, and qualitative determination of troponin I, creaInvest Clin 57(4): 352 363, 2016 Corresponding author: Trino Baptista. Departamento de Fisiología, Facultad de Medicina, Universidad de Los Andes, Mérida, Venezuela. Email: trinbap@yahoo.com. Miocarditis inducida por clozapina durante la evaluación observacional, transversal y lon...