Clozapine-Induced Myocarditis: Recognizing a Potentially Fatal Adverse Reaction

Hatton, Jennifer L.; Bhat, Pradeep; Gandhi, Sanjay

doi:10.14503/thij-13-3633

Cited by 18 publications

(15 citation statements)

References 13 publications

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“…5 Described in the literature, the exact mechanism for the cause is unknown, although it is potentially thought to be due to an IgE-mediated hypersensitivity reaction (based on endomyocardial biopsies showing eosinophilic infiltrate) or elevated plasma norepinephrine levels (a consistent effect of clozapine). 12 A retrospective review of the known clozapine myocarditis cases found that with removal of clozapine and myocarditis treatment, at least 50% of patients recover from the disease. 8 Other drugs commonly implicated in myocarditis include illicit medications (amphetamines, cocaine), antibiotics (penicillin, tetracycline), sulfonamides, and antiseizure medications (phenytoin).…”

Section: Discussionmentioning

confidence: 99%

40-Year-Old Man With Fatigue, Dyspnea, and Nausea

Fuente

Hicks

Anavekar

2019

Mayo Clinic Proceedings

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A 40-year-old white man with bipolar I disorder, neurolepticinduced parkinsonism, and nonmalignant catatonia presented with a 2-day history of worsening fatigue, dyspnea, and nausea. He had been admitted to the psychiatric unit 3 weeks previously for catatonia, where he gradually improved following medication adjustments. Specifically, risperidone was tapered off and replaced by clozapine to minimize extrapyramidal effects. He continued to improve, showing independence both in his activities of daily living and other self-cares. However, amid his progress, he experienced fatigue, dyspnea, and nausea, warranting further evaluation. At the time of the current presentation, he had no known exposures or sick contacts. He had never smoked and had no notable family history of any medical problems.Vitals were notable for a temperature of 39.5 C, heart rate of 121 beats/min, blood pressure of 122/73 mm Hg, respiratory rate of 16 breaths/min, and oxygen saturation of 93% while breathing room air. Physical examination revealed a flushed, inattentive man lying in bed. Notably, he was quite lethargic, which was an acute change compared to his mental state on the previous day. Cardiac examination revealed a regular rhythm with no appreciable jugular venous distention or lower extremity peripheral edema. Pulmonary, abdominal, neurologic, and skin examination findings were within normal limits. Laboratory evaluation yielded the following results (reference ranges provided parenthetically): hemoglobin, 14.4 g/dL (13.2-16.6 g/dL); leukocytes, 13.1 0.8 mg/dL (0.74-1.35 mg/dL); thyroidstimulating hormone, 0.5 mIU/L (0.3-4.2 mIU/L); and C-reactive protein, 62.1 mg/ L ( 8.0 mg/L). His troponin T level increased from 0.09 ng/dL (<0.04 ng/mL) at initial measurement to 0.2 ng/dL at 3 hours and 0.33 ng/dL at 6 hours. During this time, he reported no chest pain, pressure, or discomfort. Results of urinalysis and blood cultures were unremarkable. Polymerase chain reaction was negative for influenza A and B and respiratory syncytial virus.Chest radiography revealed no consolidation, pleural effusion, cardiomegaly, or signs of heart failure. Initial electrocardiography (ECG) showed only sinus tachycardia with no ST-T wave abnormalities. Transthoracic echocardiography (TTE) was notable for generalized hypokinesis with a calculated ejection fraction of 43% and normal right ventricular size, function, and pulmonary pressures. No previous echocardiograms were available because the patient had never undergone echocardiography.

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Section: Discussionmentioning

confidence: 99%

40-Year-Old Man With Fatigue, Dyspnea, and Nausea

Fuente

Hicks

Anavekar

2019

Mayo Clinic Proceedings

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“…Since CLZ is the only antipsychotic with a defined efficacious clinical range, analyzing CLZ blood levels in patients easily and accurately provides important information about the clinical range. For example, CLZ serum levels that are higher than 600 ng mL −1 (1.84 µmol L −1 ) have been associated with severe side effects, toxicity, seizure, and myocarditis . However, psychiatrists estimate that CLZ blood levels should be higher than a 350 ng mL −1 (1.07 µmol L −1 ) threshold level to achieve effective treatment .…”

Section: Introductionmentioning

confidence: 99%

A Chitosan–Carbon Nanotube‐Modified Microelectrode for In Situ Detection of Blood Levels of the Antipsychotic Clozapine in a Finger‐Pricked Sample Volume

Shukla

Ben‐Yoav

2019

Adv Healthcare Materials

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addition, CLZ is the only antipsychotic drug currently approved for treatmentresistant schizophrenia. The FDA has recently permitted greater flexibility in deciding whether to continue or rechallenge CLZ in patients. [2] However, CLZ, although a common evidence-based treatment in the field of mental health, is underutilized. The monitoring of CLZ is burdensome and involves frequent invasive blood draws and its treatment efficacy is suboptimal due to the difficulty in titrating its dose, since over dosage results in toxicity as well as possible side effects such as weight gain, blurred vision, confusion, fever, sweating, and dizziness. [3][4][5] Since CLZ is the only antipsychotic with a defined efficacious clinical range, [6,7] analyzing CLZ blood levels in patients easily and accurately provides important information about the clinical range. For example, CLZ serum levels that are higher than 600 ng mL −1 (1.84 µmol L −1 ) have been associated with severe side effects, toxicity, seizure, and myocarditis. [8][9][10][11][12][13][14] However, psychiatrists estimate that CLZ blood levels should be higher than a 350 ng mL −1 (1.07 µmol L −1 ) threshold level to achieve effective treatment. [15,16] Therefore, clinicians have been advocating therapeutic drug monitoring (TDM) for CLZ therapy [9,17] that can be rapidly done at the point-of-care (PoC), such as at the physician's office or at home. Along the lines of the medical treatment revolution that the glucose finger-prick blood test provided for diabetes patients, in situ analysis of CLZ blood levels in microliter samples would enable rapid CLZ detection in finger-pricked blood of schizophrenia patients. Such a blood test would provide rapid assessment of CLZ treatment efficacy, which would better manage schizophrenia treatment and care.Current analytical methods for TDM of CLZ blood levels have limited capabilities to rapidly measure CLZ levels in microliter samples. [18][19][20][21][22][23][24][25][26] Liquid chromatography, followed by tandem mass spectrometry (LC-MS/MS), [23] is the gold standard and is available in commercial laboratories. A variation of the method used for venous blood has been adapted to low-volume capillary blood using dried blood spot testing. [24,25] Briefly, the sample is dehydrated on filter paper, transferred to an analytical laboratory, and rehydrated for further analysis using an LC-MS/MS. Although the LC-MS/MS method provides The antipsychotic clozapine is the most effective medication available for schizophrenia and it is the only antipsychotic with a known efficacious clinical range. However, it is dramatically underutilized due to the inability to test clozapine blood levels in finger-pricked patients' samples. This prevents obtaining immediate blood levels information, resulting in suboptimal treatment. The development of an electrochemical microsensor is presented, which enables, for the first time, clozapine detection in microliters volume whole blood. The sensor is based on a microelectrode modified with micrometer-thick biop...

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“…Clinicians should also consider the possibility of less common but more serious side effects such as agranulocytosis, cardiomyopathy and myocarditis 12 13. Clozapine is also associated with gastrointestinal hypomotility which has the potential to be life-threatening 14…”

Section: Introductionmentioning

confidence: 99%

Clozapine-induced dysphagia with secondary substantial weight loss

Osman¹,

Devadas

2016

BMJ Case Reports

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Dysphagia is listed as a 'rare' side effect following clozapine treatment. In this case report, we describe how significant clozapine-induced dysphagia has led to significant reduction of nutritional intake with subsequent substantial weight loss. An 18-year-old single man with an established diagnosis of treatment-resistant paranoid schizophrenia recovered well on a therapeutic dose of clozapine. However, he was noted to lose weight significantly (up to 20% of his original weight) as the dose was uptitrated. This was brought about by development of dysphagia, likely to be due to clozapine. Addition of nutritional supplementary liquids and initiation of a modified behavioural dietary/swallowing programme, while repeatedly mastering the Mendelsohn manoeuvre technique, alleviated the swallowing difficulties and restored his weight.

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Clozapine-Induced Myocarditis: Recognizing a Potentially Fatal Adverse Reaction

Cited by 18 publications

References 13 publications

40-Year-Old Man With Fatigue, Dyspnea, and Nausea

40-Year-Old Man With Fatigue, Dyspnea, and Nausea

A Chitosan–Carbon Nanotube‐Modified Microelectrode for In Situ Detection of Blood Levels of the Antipsychotic Clozapine in a Finger‐Pricked Sample Volume

Clozapine-induced dysphagia with secondary substantial weight loss

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