clozapine and Death--Sudden--Cardiac

To review the published literature on serious adverse cardiac events associated with the atypical antipsychotic agent, clozapine, and to make recommendations for cardiac assessment of candidates for clozapine treatment and for monitoring of cardiac status after treatment is initiated.. We searched the PubMed and MEDLINE databases for articles published from 1970 to 2004 that contain the keywords "clozapine and myocarditis," "clozapine and cardiomyopathy," "clozapine and cardiotoxicity," "clozapine and sudden death" or "clozapine and mortality." We also manually searched the bibliographies of these articles for related sources.. We reviewed the 30 case reports, case series, laboratory and clinical trials, data mining studies, and previous reviews identified by this search.. Recent evidence suggests that clozapine is associated with a low (0.015% to 0.188%) risk of potentially fatal myocarditis or cardiomyopathy. The drug is not known to be independently associated with pathologic prolongation of the QTc interval, but it may contribute to pathologic QTc prolongation in patients with other risk factors for this condition.. The low risk of a serious adverse cardiac event should be outweighed by a reduction in suicide risk for most patients taking clozapine. We provide recommendations for assessing and monitoring cardiac status in patients prior to and after initiation of treatment with clozapine.

Topics: Antipsychotic Agents; Cardiomyopathies; Clozapine; Death, Sudden, Cardiac; Heart Diseases; Humans; Myocarditis

Explainable sudden deaths in schizophrenia patients due to both cardiac (SCD) and non-cardiac causes (SNCD) have been extensively documented. However, sudden unexplained death (SUD) in this cohort remains to be elucidated. This study retrospectively analyzed 18 SUD cases that underwent systematic autopsy at our institutes during the period 2010-2022. The etiological, demographic, and autopsy features of the SUD cases were then compared with 37 year-matched sudden explainable deaths (23 SCD cases and 14 SNCD cases). Our results showed that the average age of the SUD was 39.0 ( ± 8.4) years, with the disease duration of 11.8 ( ± 8.1) years and a male/female ratio of 11:7. Most cases occurred during daytime (72.2%) and outside of hospital (77.8%). A large proportion of the SUD cases (77.8%) had persistent psychiatric episodes before death. Clozapine was found to be the most commonly used antipsychotic (33.3%), followed by Olanzapine (27.8%), Risperidone (27.8%) and Chlorpromazine (27.8%) in the SUD cases. When compared among groups, the SUD cases showed significantly younger ages (p = 0.035), lower heart weight (p = 0.004) and lower proportion of Clozapine use (p = 0.045). The presence of persistent psychiatric episodes was significantly higher in the SUD group than in any explainable deaths (p = 0.018) and was an independent risk factor for SUD (OR = 4.205, p = 0.040). This is the first autopsy-based study of SUD cases from China. We conclude that a stable mental state maintained by antipsychotics (i.e., Clozapine) is vital to schizophrenia patients.

Topics: Adult; Antipsychotic Agents; Autopsy; China; Clozapine; Death, Sudden, Cardiac; Female; Humans; Male; Middle Aged; Retrospective Studies; Schizophrenia

Clozapine is the cornerstone of therapy for refractory schizophrenia; however, the potential for cardiotoxicity is an important limitation in its use. In the current analysis we sought to evaluate the long term cardiac outcomes of clozapine therapy.. All-cause mortality, incidence of sudden death and time to myocarditis were assessed in a cohort of patients maintained on clozapine between January 2009 and December 2015. All patients had regular electrocardiograms, complete blood count, clozapine levels and echocardiography as part of a formal protocol.. A total of 503 patients with treatment-resistant schizophrenia were maintained on clozapine during the study period of which 93 patients (18%) discontinued therapy with 29 (6%) deaths. The incidence of sudden death and myocarditis were 2% (n=10) and 3% (n=14) respectively. Amongst patients with sudden death, 7 out of 10 (70%) were documented to have used illicit drugs prior to death, with a tendency to weight gain also noted. The mean time to myocarditis post clozapine commencement was 15±7days. The reduction in left ventricular ejection fraction in those with myocarditis was 11±2%.. Myocarditis and sudden cardiac death are uncommon but clinically important complications in a cohort of patients followed while maintained on clozapine undergoing regular cardiac assessment. Further studies are required to document the role of preventive measures for left ventricular dysfunction and sudden cardiac death in this population.

Topics: Adult; Aged; Antipsychotic Agents; Australia; Clozapine; Cohort Studies; Death, Sudden, Cardiac; Electrocardiography; Female; Humans; Incidence; Male; Middle Aged; Myocarditis; Prospective Studies; Time Factors

The case concerns the sudden death of a 29-year-old male during clozapine therapy started 2 weeks before. He had a history of treatment-resistant chronic schizophrenia. A complete immunohistochemical study was performed on heart specimens. Histologically, the heart presented diffuse eosinophilic infiltrates located around perivascular structures and focal myocyte necrosis with numerous interstitial eosinophils admixed with histiocytes. The diagnosis of acute myocarditis with an eosinophilic infiltrate was established as the cause of death. The autopsy findings and a detailed medical history supported the conclusion that clozapine-induced hypersensitivity myocarditis was the most likely cause of death.

Topics: Adult; Antipsychotic Agents; Clozapine; Death, Sudden, Cardiac; Fatal Outcome; Humans; Hypersensitivity, Delayed; Male; Myocarditis; Schizophrenia

To examine the rates of cardiac arrest and ventricular arrhythmia in patients with treated schizophrenia and in non-schizophrenic controls.. Cohort study of outpatients using administrative data.. 3 US Medicaid programmes.. Patients with schizophrenia treated with clozapine, haloperidol, risperidone, or thioridazine; a control group of patients with glaucoma; and a control group of patients with psoriasis.. Diagnosis of cardiac arrest or ventricular arrhythmia.. Patients with treated schizophrenia had higher rates of cardiac arrest and ventricular arrhythmia than controls, with rate ratios ranging from 1.7 to 3.2. Overall, thioridazine was not associated with an increased risk compared with haloperidol (rate ratio 0.9, 95% confidence interval 0.7 to 1.2). However, thioridazine showed an increased risk of events at doses > or =600 mg (2.6, 1.0 to 6.6; P=0.049) and a linear dose-response relation (P=0.038).. The increased risk of cardiac arrest and ventricular arrhythmia in patients with treated schizophrenia could be due to the disease or its treatment. Overall, the risk with thioridazine was no worse than that with haloperidol. Thioridazine may, however, have a higher risk at high doses, although this finding could be due to chance. To reduce cardiac risk, thioridazine should be prescribed at the lowest dose needed to obtain an optimal therapeutic effect.

Topics: Adult; Aged; Antipsychotic Agents; Arrhythmias, Cardiac; Clozapine; Cohort Studies; Confidence Intervals; Death, Sudden, Cardiac; Female; Haloperidol; Heart Arrest; Humans; Male; Medicaid; Middle Aged; Risperidone; Schizophrenia; Thioridazine; United States

Antipsychotic medications cause a wide range of adverse effects and have been associated with sudden death in psychiatric patients.. To supply power spectral analysis of heart rate variability as a tool to examine the arrythmogenic effects of neuroleptics.. Heart rate analysis was carried out in patients with schizophrenia on standard doses of neuroleptic monotherapy -- 21 were on clozapine, 18 on haloperidol and 17 on olanzapine -- and in 53 healthy subjects.. Patients with schizophrenia on clozapine had significantly higher heart rate, lower heart rate variability and lower high-frequency and higher low-frequency components compared with patients on haloperidol or olanzapine and matched control subjects. Prolonged QTc intervals were more common in patients than controls.. Patients treated with neuroleptic medications, especially clozapine, showed autonomic dysregulation and cardiac repolarisation changes. Physicians should be aware of this adverse reaction.

Topics: Adult; Analysis of Variance; Antipsychotic Agents; Autonomic Nervous System Diseases; Case-Control Studies; Clozapine; Death, Sudden, Cardiac; Electrocardiography; Female; Heart Rate; Humans; Male; Middle Aged; Schizophrenia

Topics: Animals; Antipsychotic Agents; CHO Cells; Clozapine; Cricetinae; Death, Sudden, Cardiac; Humans; Long QT Syndrome

Topics: Antipsychotic Agents; Clozapine; Death, Sudden, Cardiac; Drug Combinations; Humans; Male; Reproducibility of Results; Selective Serotonin Reuptake Inhibitors; Sertraline

Topics: Antipsychotic Agents; Cardiomyopathies; Clozapine; Death, Sudden, Cardiac; Humans; Myocarditis; Risk Factors

Topics: Antipsychotic Agents; Clozapine; Death, Sudden, Cardiac; Humans; Risk Factors

Topics: Antipsychotic Agents; Clozapine; Death, Sudden, Cardiac; Humans; Myocarditis; Risk Factors

Topics: Adult; Antipsychotic Agents; Cardiomyopathies; Clozapine; Death, Sudden, Cardiac; Factor V; Female; Humans; Myocarditis; Pulmonary Embolism; Risk Factors; Schizophrenia

Topics: Adult; Aged; Antipsychotic Agents; Cardiomyopathies; Clozapine; Death, Sudden, Cardiac; Drug Hypersensitivity; Female; Humans; Male; Myocarditis; Parkinson Disease; Schizophrenia