Hearts and Minds:Real-Life Cardiotoxicity with Clozapine in Psychosis

Schizophrenia has a 1% prevalence in the population; 30% of these patients are treatment refractory. Clozapine is the only drug licensed to treat treatment refractory psychosis, but concerns about potential adverse effects result in only a proportion of eligible patients being treated. Although a well-documented neutropenia risk is mitigated by routine blood testing, cardiac toxicity is a commonly cited reason to discontinue clozapine treatment. However, there is little data on the real-life cardiac outcomes in those receiving clozapine treatment. Retrospective review of electrocardiogram, echocardiogram, and clinical outcomes in 39 inpatients with treatment-refractory schizophrenia, treated with clozapine and other antipsychotic medication, referred for cardiology opinion. Commonest reasons for referral were development of left ventricular (LV) impairment or sinus tachycardia with normal LV function. Patients were reviewed by a range of cardiologists, receiving varied interventions.Median LV ejection fraction in the clozapine group was normal (52%). Serial echocardiograms demonstrated that clozapine-treated patients with LV impairment had no change in LV ejection fraction over a 4-month follow-up. Left ventricular ejection fraction did not differ between patients treated with clozapine and other antipsychotics. However, over an 11-year follow-up period, 48% of patients had discontinued clozapine treatment. This naturalistic study demonstrates that clozapine is not associated with significant cardiac mortality or morbidity. There is a real need for multidisciplinary working between specialist cardiologists and psychiatrists caring for these complex patients to facilitate optimal long-term physical and mental health outcomes

The effect of antidepressant medications in the management of heart failure on outcomes: mortality, cardiovascular function and depression - a systematic review

Depression is associated with increased morbidity, mortality and hospital readmission in patients with heart failure (HF). This systematic review aimed to compile studies examining whether the use of antidepressants could improve outcome in patients with HF and concomitant depression. The electronic libraries Embase, OVID MEDLINE(R) and PsychInfo were used to search the following terms 'heart failure' AND 'anti-depressants'; 'heart failure' AND 'TCA' OR 'SSRI' OR 'SNRI'. The result of this database search was analysed to select papers that satisfied our inclusion criteria. Of the 180 papers found in the original database search, only three met the inclusion criteria. A further two papers were added from hand-searching through the references. Three of these papers are randomised controlled trials (RCT); the other two, cohort studies. All studies show that antidepressants are well tolerated in this group. There was no significant difference in depressive symptoms between the test and placebo. The cardiac outcomes of patients with HF are not improved by the use of antidepressants relative to placebo. Antidepressants are not associated with increased mortality rate as established in previous papers. However, there is inadequate evidence that the use of antidepressants effects significant improvement in depression or cardiac outcomes.peer-reviewe

The effect of antidepressant medications in the management of heart failure on outcomes: mortality, cardiovascular function and depression - a systematic review

Depression is associated with increased morbidity, mortality and hospital readmission in patients with heart failure (HF). This systematic review aimed to compile studies examining whether the use of antidepressants could improve outcome in patients with HF and concomitant depression. The electronic libraries Embase, OVID MEDLINE(R) and PsychInfo were used to search the following terms \u27heart failure\u27 AND \u27anti-depressants\u27; \u27heart failure\u27 AND \u27TCA\u27 OR \u27SSRI\u27 OR \u27SNRI\u27. The result of this database search was analysed to select papers that satisfied our inclusion criteria. Of the 180 papers found in the original database search, only three met the inclusion criteria. A further two papers were added from hand-searching through the references. Three of these papers are randomised controlled trials (RCT); the other two, cohort studies. All studies show that antidepressants are well tolerated in this group. There was no significant difference in depressive symptoms between the test and placebo. The cardiac outcomes of patients with HF are not improved by the use of antidepressants relative to placebo. Antidepressants are not associated with increased mortality rate as established in previous papers. However, there is inadequate evidence that the use of antidepressants effects significant improvement in depression or cardiac outcomes

Clozapine in a patient with treatment-resistant schizophrenia and hypertrophic cardiomyopathy:A case report

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. His psychiatric illness was characterised by multimodal hallucinations and delusions combined with low mood and poor motivation. The diagnosis of HCM was made 3 years previously following a routine electrocardiogram (ECG), and he had remained asymptomatic throughout this time; there were concerns about the risk of initiating clozapine given his pre-existing cardiac condition. Baseline investigations were performed as per local guidelines prior to commencing clozapine; these were within normal limits other than a mildly raised troponin level of 54 ng/L (normal <16 ng/L), which was attributed to the HCM. In addition, baseline transthoracic echocardiography (TTE) was performed which showed no change in the structural heart disease in comparison with previous TTEs. Clozapine was started at 12.5 mg daily and up-titrated to 150 mg twice daily over 14 days as per our institute’s guidelines. The patient was monitored with regular testing of troponins, inflammatory markers and ECG. On day 18, the troponin level increased to 1371 ng/L. Creatine kinase and inflammatory markers remained stable. No changes in ECG or TTE were noted and the patient remained clinically asymptomatic. Cardiology opinion was sought and reported that the finding of an isolated elevated troponin was likely to reflect a ‘troponin leak’ in the context of increased cardiac muscle mass associated with HCM. In the absence of any clinical compromise, it was not felt to be of concern. Clozapine was continued with good effect on mental state. Troponin levels gradually reduced and the patient remained well. CONCLUSIONS: While multiple cases of clozapine-induced cardiotoxicity have been reported in the literature, its implications for pre-existing structural disease are unclear. This case report suggests that clozapine can be safely introduced in pre-existing HCM, explores strategies for monitoring and highlights the importance of liaising with experienced cardiologists. DECLARATION OF INTEREST: None. COPYRIGHT AND USAGE: © The Royal College of Psychiatrists 2016. This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) license

Understanding and managing cardiac side-effects of second-generation antipsychotics in the treatment of schizophrenia

Second-generation antipsychotic medications (SGAs) have advanced the treatment of schizophrenia over the past 30 years. However, a number of potentially life-threatening cardiac side-effects associated with these treatments concern and can discourage prescribers from administering these evidence-based treatments. This review provides a practical, psychiatrist-oriented understanding of the relative frequencies, mechanisms, investigations and treatments associated with these cardiac toxicities. We aim to highlight that these are relatively rare complications of an effective class of drug and to promote the advantages of early involvement of cardiologists in the psychiatric multidisciplinary team to guide the investigation and management of these conditions

Clozapine and cardiotoxicity – A guide for psychiatrists written by cardiologists

This review discusses the rare but potentially life-threatening cardiovascular side-effects of myocarditis and dilated cardiomyopathy associated with the use of Clozapine. The clinical presentation of these conditions is non-specific, making it difficult to both risk-stratify and identify patients who develop these consequences. This review aims to examine the proposed aetiologies, diagnostic approaches and subsequent management strategies of cardiotoxicity associated with clozapine use; offering guidance to psychiatrists and general physicians. Current evidence highlights the importance of accurate diagnosis to prevent premature and unnecessary cessation of clozapine. Guidance on monitoring and reintroduction of the drug is emerging and current practice recommends a combination of regular monitoring of biomarkers and imaging to make a diagnosis of cardiotoxicity although further work is needed to establish evidence-based guidelines

Understanding and managing cardiac side-effects of second-generation antipsychotics in the treatment of schizophrenia

SUMMARY Second-generation antipsychotic medications (SGAs) have advanced the treatment of schizophrenia over the past 30 years. However, a number of potentially life-threatening cardiac side-effects associated with these treatments concern and can discourage prescribers from administering these evidence-based treatments. This review provides a practical, psychiatrist-oriented understanding of the relative frequencies, mechanisms, investigations and treatments associated with these cardiac toxicities. We aim to highlight that these are relatively rare complications of an effective class of drug and to promote the advantages of early involvement of cardiologists in the psychiatric multidisciplinary team to guide the investigation and management of these conditions. LEARNING OBJECTIVES After reading this article you will be able to: � understand the relative incidence of cardiotoxic side-effects of the various SGAs� perform preliminary investigations to diagnose the common cardiotoxic side-effects of SGAs� understand the treatments for these cardiac side-effects and the role of cardiologists involved the care of these patients