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Clozapine cardiac effects

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...
September 30, 2016: 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
Yael Midbari, Tanya Ebert, Ira Kosov, Moshe Kotler, Abraham Weizman, Anca Ram
OBJECTIVE: There are very few studies in the literature regarding clozapine use in children <13 years of age. In this retrospective chart review, we compared the safety of clozapine--as determined by hematological and cardiometabolic changes - to that of non-clozapine antipsychotics used in the treatment of childhood-onset schizophrenia (COS). METHODS: The clozapine treatment group (CTG) consisted of 17 COS patients (mean age 10.4 ± 2 years) who were hospitalized in a psychiatric ward between the years 2005 and 2012...
October 2013: Journal of Child and Adolescent Psychopharmacology
Zana R Majeed, Charles D Nichols, Robin L Cooper
The fruit fly, Drosophila melanogaster, is a good experimental organism to study the underlying mechanism of heart rate (HR) regulation. It is already known that many neuromodulators (serotonin, dopamine, octopamine, acetylcholine) change the HR in Drosophila melanogaster larvae. In this study, we investigated the role of cAMP-PKA signaling pathway in HR regulation and 5-HT positive chronotropic action. In order to obtain insight into the 5-HT mechanism of action in larvae cardiomyocytes, genetic and pharmacological approaches were used...
December 2013: Journal of Applied Physiology
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. Re-challenge 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...
September 18, 2013: Clinical Schizophrenia & related Psychoses
Tariq Munshi, Mir Mazhar, Tariq Hassan
We describe a case of a patient whose clozapine was discontinued after a "red result" following R-CHOP (rituximab with cyclophosphamide, hydroxydaunorubicin, Oncovin, and prednisolone) chemotherapy for large B-cell lymphoma. In some cases, manufacturers grant permission, on compassionate grounds, for clozapine to be continued or reinitiated following assessment by their consultant hematologist. Other than a recent case report, there is not much literature surrounding this medical issue. However, since the two leading causes of mortality in schizophrenia are cancer and cardiac disease, this is not an uncommon occurrence...
2013: Neuropsychiatric Disease and Treatment
(no author information available yet)
Several detailed case reports have described cardiac muscle disorders (cardiomyopathy and myocarditis) in patients treated with quetiapine, some of which have been fatal. The symptoms included shortness of breath and oedema. The disorders sometimes resolved on withdrawal of quetiapine. Quetiapine is chemically similar to clozapine and olanzapine, which are known to sometimes provoke this type of adverse effect. In practice, a patient who develops dyspnoea or other signs of heart failure during quetiapine therapy may benefit if the drug's role is recognised and quetiapine withdrawn...
July 2013: Prescrire International
Kathlyn J Ronaldson, Paul B Fitzgerald, Andrew J Taylor, Duncan J Topliss, Rory Wolfe, John J McNeil
BACKGROUND: Despite the implementation of cardiac monitoring guidelines, clozapine-induced myocarditis continues to cause deaths in Australia, and the risk is a barrier to prescription of this effective drug for the treatment of schizophrenia. This study was designed to identify clinical and phenotypic risk factors for clozapine-induced myocarditis. METHOD: Possible cases of clozapine related myocarditis occurring between June 1993 and November 2009 and a comparative group of controls taking clozapine for at least 45days without cardiac disease were documented from the patients' medical records...
November 2012: Schizophrenia Research
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