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Clozapine cardiac effects

Natraj Katta, Sudarshan Balla, Kul Aggarwal
Hypersensitivity myocarditis is a rare but serious adverse effect of clozapine, a commonly used psychiatric drug. We report the case of sudden cardiac death from clozapine-induced hypersensitivity myocarditis diagnosed at autopsy. A 54-year-old Caucasian male on clozapine therapy for bipolar disorder presented with a sudden onset of shortness of breath. Laboratory studies were significant for elevated N-terminal prohormone of brain natriuretic peptide. During his hospital stay, the patient died of sudden cardiac arrest from ventricular tachycardia...
October 2016: Autopsy & case reports
Leonard Kritharides, Vincent Chow, Tim Jr Lambert
Patients with schizophrenia die on average 25 years earlier than the general population, and this gap appears to be increasing. Most of the excess mortality is due to premature cardiovascular deaths rather than suicide. Many psychotropic agents are orexigenic and can increase weight and promote dyslipidaemia. Traditional cardiac risk factors are undertreated among patients with schizophrenia, and they are less likely to receive cardiac revascularisation than those without a mental illness. Clozapine is an atypical antipsychotic medication effective for treatment of refractory schizophrenia, but is associated with the risk of myocarditis and cardiomyopathy...
February 6, 2017: Medical Journal of Australia
Asiel Yair Adan Sanchez, Jessica J Foster, Carla M Plymen, Sukhi Shergill
BACKGROUND: There is currently limited experience in the initiation and maintenance of clozapine for treatment-resistant psychosis in adults with established structural heart disease. These complex patients require close supervision and liaison between colleagues. Here we present the successful experience of treating one such patient within our service and describe a monitoring plan to ensure that these treatments can be provided both safely and effectively. CASE PRESENTATION: A 36-year-old man with treatment-resistant schizophrenia and known hypertrophic cardiomyopathy (HCM) was admitted to a specialist unit for a trial of clozapine...
November 2016: BJPsych Open
Tiziano Acciavatti, Giovanni Martinotti, Mariangela Corbo, Eduardo Cinosi, Matteo Lupi, Fabrizio Ricci, Rosa Di Scala, Emilia D'Ugo, Viola De Francesco, Raffaele De Caterina, Massimo di Giannantonio
OBJECTIVE: We aimed to investigate in a clinical setting, the effects of different classes of psychotropic drugs on cardiac electrophysiological measures linked with an increased risk of sudden cardiac death. METHODS: We conducted a cross-sectional study in a population of 1059 psychiatric inpatients studying the effects of various psychotropic drugs on the T-peak to T-end (TpTe) interval, QT dispersion and QT interval. RESULTS: Methadone use showed a strong association with TpTe prolongation (odds ratio (OR)=12...
April 2017: Journal of Psychopharmacology
Charilaos Gerasimou, Georgia Phaedra Vitali, George D Vavougios, Charalabos Papageorgiou, Athanasios Douzenis, Styliani I Kokoris, Ioannis Liappas, Emmanouil Rizos
BACKGROUND: Clozapine is a second-generation antipsychotic drug used in treatment-resistant schizophrenia. Fever induced by clozapine is a rather frequent side-effect which usually occurs in the first 4 weeks of treatment. Despite its effectiveness, there are potentially life-threatening adverse effects, such as cardiotoxicity. CASE REPORT: We present the case of a 31-year-old caucasian male with refractory schizophrenia who developed benign fever, increase of C-reactive protein and high troponin levels, without presenting any other signs to myocarditis, on the 13th day under clozapine treatment, which declined progressively upon discontinuation of the drug...
January 2, 2017: In Vivo
Vincenzo Prisco, Petrosino Monica, Germano Fiore, Annamaria Tridente, Antonietta La Rocca, Francesco Catapano, Michele Fabrazzo
Clozapine-related pericarditis is a rare side effect of the drug. We reported the clinical cases of two women, aged 22 and 28 years, affected by schizophrenia with pericarditis symptoms related to clozapine treatment of 200 mg/day. Clozapine was discontinued in both patients, resulting in normalization of the ECG changes, and echocardiography confirmed the progressive disappearance of the pericardial effusion. Interestingly, while inflammatory indices and pro-brain natriuretic peptide (pro-BNP) plasma levels were high in both patients, only one of them showed tachycardia, subjective chest pain, shortness of breath and dyspnea, with a clinical symptomatology suggesting a cardiac involvement...
December 20, 2016: Clinical Schizophrenia & related Psychoses
Cristobal Manuel Rodríguez-Leal, Elena López-Lunar, Jose Manuel Carrascosa-Bernáldez, Rosa Maria Provencio-Arranz
OBJECTIVE: To describe a new initiative developed to optimise patient safety in a mental health setting in order to prevent serious cardiac events. MATERIALS AND METHODS: A longitudinal study of all in-patients admitted at the hospital, comprised of 197 beds distributed among three units, was conducted for 12 months. All admitted patients at the hospital underwent electrocardiogram surveillance, as it was described in our new local guideline for sudden cardiac death prevention...
March 2017: International Journal of Psychiatry in Clinical Practice
Charles H Earnshaw, Lucy Powell, Owen Haeney
A Caucasian male in his early twenties suffering from treatment resistant schizophrenia was started on clozapine. After three days he developed tachycardia, a common side effect of clozapine induction. He had one temperature spike (38.9°C) on day ten after induction but remained clinically well. An ECG and blood tests were normal. Due to persistent tachycardia and an episode of collapse whilst seated on day 12, he was admitted to hospital for further investigation. A diagnosis of myocarditis was confirmed as a result of elevated cardiac enzyme levels and an echocardiogram...
2016: Case Reports in Psychiatry
Pichai Ittasakul, Anthony Archer, Jennifer Kezman, Wanlop Atsariyasing, Morris B Goldman
Clozapine is an atypical antipsychotic which is often effective in patients who fail to respond to other antipsychotics, but its use carries substantial risk. Myocarditis is one of the life-threatening adverse effects, which occurs in about 1% of exposed patients. Rechallenge with clozapine is controversial, particularly shortly after the occurrence of the myocarditis, and when there is clear and convincing evidence of cardiac damage. Aggressive use of clozapine, however, may be critical for the recovery of patients early in the course of their illness...
2016: Clinical Schizophrenia & related Psychoses
Martina Curto, Nicoletta Girardi, Luana Lionetto, Giuseppino M Ciavarella, Stefano Ferracuti, Ross J Baldessarini
Clozapine is exceptionally effective in psychotic disorders and can reduce suicidal risk. Nevertheless, its use is limited due to potentially life-threatening adverse effects, including myocarditis and cardiomyopathy. Given their clinical importance, we systematically reviewed research on adverse cardiac effects of clozapine, aiming to improve estimates of their incidence, summarize features supporting their diagnosis, and evaluate proposed monitoring procedures. Incidence of early (≤2 months) myocarditis ranges from <0...
July 2016: Current Psychiatry Reports
A Heranval, R Lefaucheur, D Fetter, A Rouillé, F Le Goff, D Maltête
INTRODUCTION/OBJECTIVE: Drugs with potential cardiac adverse effects are commonly prescribed in Parkinson's disease (PD). To describe demographic and clinical characteristics in a group of PD patients with cardiac events and to evaluate risk factors. PATIENTS AND METHODS: We sampled 506 consecutive PD patients (211 women/295 men), median age 68.3±10.6 years (range 36-95) and median disease duration 11.2±6.5 years (range 1-49). Medications with potential cardiac effects, i...
April 2016: Revue Neurologique
Ruili Dang, Yujin Guo, Hualin Cai, Ranyao Yang, Donglou Liang, Chuanfeng Lv, Pei Jiang
Patients with schizophrenia (SCZ) are at higher risk for developing cardiovascular disease (CVD) and neuregulin-1 (NRG1)/ErbB signaling has been identified as a common susceptibility pathway for the comorbidity. Antipsychotic treatment can change NRG1/ErbB signaling in the brain, which has been implicated in their therapeutic actions, whereas the drug-induced alterations of NRG1/ErbB pathway in cardiovascular system might be associated with the prominent cardiac side-effects of antipsychotic medication. To test this hypothesis, we examined NRG1/ErbB system in rat prefrontal cortex (PFC) and myocardium following 4-week intraperitoneal administration of haloperidol, risperidone or clozapine...
April 2016: Journal of Toxicological Sciences
Birmay Çam, Leyla Gülseren, Levent Mete, Şeref Gülseren
OBJECTIVE: Atrial fibrillation is a serious side effect of antipsychotic drugs, it is very rare but can be fatal. In this case report, a subject who developed an atrial fibrillation after receiving clozapine and olanzapine has been presented. CASE: A 49 year-old female patient with a 10-year history of schizophrenia with no additional disease history was admitted to the hospital with the diagnosis of schizophrenia. Clozapine was started to be given as 12,5 mg/day and then it was gradually increased for the patient...
2015: Türk Psikiyatri Dergisi, Turkish Journal of Psychiatry
Basel A Abdel-Wahab, Metwally E Metwally
Safety concerns have been raised about clozapine-induced cardiotoxicity particularly in young patients. The exact mechanism of clozapine cardiotoxicity has not yet been thoroughly studied. This study aimed to investigate the possible mechanisms of clozapine-induced cardiotoxicity in a rat model. Young male Wistar rats were treated with clozapine (10, 15 and 25 mg/kg/day, i.p.) for 21 days. Haemodynamic and echocardiographic studies were performed for assessment of cardiac functions. Heart sections were studied histopathologically and immunohistochemically...
October 2015: Cardiovascular Toxicology
K Kontoangelos, S Loizos, J Kanakakis, N Smyrnis, M Economou, J D Bergiannaki, G N Papadimitriou
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...
August 2014: European Review for Medical and Pharmacological Sciences
Hilmi Orhan
Biotransformation is one of the key elements of chemically induced toxicity. Although organisms have an intrinsic tendency to diminish the harm posed by chemical exposure with or without structural modification and excretion of the agents (detoxification), this is not always the case; toxification may also occur. The liver has evolved to be the center of biotransformation from the anatomical, physiological and biochemical points of view; it is located alongside the stomach and intestine, it receives more than 25% of the cardiac output and it contains, in general, the richest quantity but also variety of drug metabolizing enzymes...
2015: Current Medicinal Chemistry
Shin-ichi Momomura
It has been reported that a variety of cardiovascular side effects are induced by drugs, including psychotropic drugs. Among them, myocarditis/cardiomyopathy and long QT syndrome are addressed in this article. Myocarditis is due to inflammation of the myocardium, and the pericardium is also often involved. In that case, it is called myopericarditis. Myocarditis is caused by a variety of etiologies, including viruses, bacteria, inflammatory diseases, and drugs. Psychotropic drugs such as clozapine have been reported to induce myocarditis...
2014: Seishin Shinkeigaku Zasshi, Psychiatria et Neurologia Japonica
Basel A Abdel-Wahab, Metwally E Metwally, Mohamed M El-khawanki, Alaa M Hashim
Clozapine (CLZ) is the most effective therapeutic alternative in the treatment of resistant schizophrenia. However, the cardiotoxicity of CLZ, particularly in young patients, has raised concerns about its safety. Captopril is a well-known angiotensin-converting enzyme inhibitor with antioxidant properties effective in treating hypertension and heart failure. The aim of this study was to investigate the protective effect of captopril against clozapine-induced myocarditis in rats and the possible mechanisms behind this effect...
June 5, 2014: Chemico-biological Interactions
Adam P Hill, Mark J Perrin, Juliane Heide, Terence J Campbell, Stefan A Mann, Jamie I Vandenberg
The Kv11.1 potassium channel is the molecular target for the majority of drugs implicated in acquired long QT syndrome, the most common cause of drug-induced sudden cardiac death, and a common reason for drug restriction or withdrawal from the market. While the IC50 for block of Kv11.1 is commonly used to estimate the risk of acquired long QT syndrome, this approach is crude, and it is widely accepted that the kinetics of drug interactions with the channel are a critical component in understanding their mechanism of action and risk profiles...
May 2014: Molecular Pharmacology
Emanuel Raschi, Elisabetta Poluzzi, Brian Godman, Ariola Koci, Ugo Moretti, Marija Kalaba, Marion Bennie, Corrado Barbui, Bjorn Wettermark, Miriam Sturkenboom, Fabrizio De Ponti
BACKGROUND: Antipsychotics (APs) have been associated with risk of torsade de Pointes (TdP). This has important public health implications. Therefore, (a) we exploited the public FDA Adverse Event Reporting System (FAERS) to characterize their torsadogenic profile; (b) we collected drug utilization data from 12 European Countries to assess the population exposure over the 2005-2010 period. METHODS: FAERS data (2004-2010) were analyzed based on the following criteria: (1) ≥ 4 cases of TdP/QT abnormalities; (2) Significant Reporting Odds Ratio, ROR [Lower Limit of the 95% confidence interval>1], for TdP/QT abnormalities, adjusted and stratified (Arizona CERT drugs as effect modifiers); (3) ≥ 4 cases of ventricular arrhythmia/sudden cardiac death (VA/SCD); (4) Significant ROR for VA/SCD; (5) Significant ROR, combined by aggregating TdP/QT abnormalities with VA and SCD...
2013: PloS One
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