Effects of Newer Atypical Antipsychotics on Autonomic Neurocardiac Function: A Comparison Between Amisulpride, Olanzapine, Sertindole, and Clozapine

As part of a prospective clinical study investigating the effects of atypical neuroleptics on autonomic neurocardiac function (ANF), serial standardized recordings of conventional electrocardiograms and computer-calculated measurements of 5-minute resting heart rate variability (HRV) were obtained from 51 medication-free inpatients with schizophrenia (DSM-III-R-diagnosed) before and after an average of 14.1 days of treatment with amisulpride 400 mg/day (N = 12), olanzapine 20 mg/day (N = 13), sertindole 12 mg/day (N = 13), or clozapine 100 mg/day (N = 13). Reference values for the HRV data were obtained from a large group of well-matched healthy controls (N = 70). The most important findings were the following: (1) clozapine, olanzapine, and sertindole all prolonged mean frequency-corrected QTc times, which, in the case of sertindole, proved to be significant (Wilcoxon test p <0.05); (2) sertindole and clozapine significantly increased the mean resting heart rate; and (3) only clozapine significantly reduced the parasympathetic resting tone. The results of the HRV studies are discussed considering the in vitro receptor profiles of the atypical neuroleptics under study. Potential implications for the cardiac safety and tolerance of these drugs are also discussed.

[1]  E. Klieser,et al.  Cardiovascular Autonomic Reactivity in Schizophrenics under Neuroleptic Treatment: A Potential Predictor of Short-Term Outcome? , 1998, Neuropsychobiology.

[2]  H. Bazett,et al.  AN ANALYSIS OF THE TIME‐RELATIONS OF ELECTROCARDIOGRAMS. , 1997 .

[3]  G. Breithardt,et al.  Heart rate variability: standards of measurement, physiological interpretation and clinical use. Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology. , 1996 .

[4]  Dan Ziegler,et al.  Assessment of Cardiovascular Autonomic Function: Age‐related Normal Ranges and Reproducibility of Spectral Analysis, Vector Analysis, and Standard Tests of Heart Rate Variation and Blood Pressure Responses , 1992, Diabetic medicine : a journal of the British Diabetic Association.

[5]  M. Mulekar,et al.  Diminished short-term heart rate variability predicts inducible ventricular tachycardia. , 1998, Chest.

[6]  I. Whyte,et al.  Cardiotoxicity more common in thioridazine overdose than with other neuroleptics. , 1995, Journal of toxicology. Clinical toxicology.

[7]  J R Roelandt,et al.  Heart rate variability from 24-hour electrocardiography and the 2-year risk for sudden death. , 1993, Circulation.

[8]  D. Ewing,et al.  Assessment of cardiovascular effects in diabetic autonomic neuropathy and prognostic implications. , 1980, Annals of internal medicine.

[9]  Philip Seeman,et al.  Radioreceptor Binding Profile of the Atypical Antipsychotic Olanzapine , 1996, Neuropsychopharmacology.

[10]  B Lown,et al.  Neural activity and ventricular fibrillation. , 1976, The New England journal of medicine.

[11]  R. Verrier,et al.  Effect of posterior hypothalamic stimulation on ventricular fibrillation threshold. , 1975, The American journal of physiology.

[12]  J. Bigger,et al.  Baroreflex sensitivity and heart-rate variability in prediction of total cardiac mortality after myocardial infarction , 1998, The Lancet.

[13]  D. Flockhart,et al.  Prolongation of QT interval in isolated feline hearts by antipsychotic drugs. , 1998, Journal of clinical psychopharmacology.

[14]  H. Meltzer,et al.  The mechanism of action of novel antipsychotic drugs. , 1991, Schizophrenia bulletin.

[15]  A. Garson,et al.  How to measure the QT interval--what is normal? , 1993, The American journal of cardiology.

[16]  Q. Regestein,et al.  Basis for recurring ventricular fibrillation in the absence of coronary heart disease and its management. , 1976, The New England journal of medicine.

[17]  D H Singer,et al.  Heart rate variability and sudden death secondary to coronary artery disease during ambulatory electrocardiographic monitoring. , 1987, The American journal of cardiology.

[18]  R. Friedman,et al.  Prolongation of the Corrected QT and Torsades de Pointes Cardiac Arrhythmia Associated with Intravenous Haloperidol in the Medically III , 1993, Journal of clinical psychopharmacology.

[19]  P. Schwartz,et al.  Role of the Autonomic Nervous System in the Genesis of Early Ischemic Arrhythmias , 1985, Journal of cardiovascular pharmacology.

[20]  D. Claus,et al.  Heart rate variability in schizophrenic patients and changes of autonomic heart rate parameters during treatment with clozapine , 1994, Biological Psychiatry.

[21]  J. Miller,et al.  Decreased heart rate variability and its association with increased mortality after acute myocardial infarction. , 1987, The American journal of cardiology.

[22]  J. A. Gomes,et al.  ECG changes during haloperidol and pimozide treatment of Tourette's disorder. , 1987, The American journal of psychiatry.

[23]  O Odemuyiwa,et al.  Comparison of the predictive characteristics of heart rate variability index and left ventricular ejection fraction for all-cause mortality, arrhythmic events and sudden death after acute myocardial infarction. , 1991, The American journal of cardiology.

[24]  B. Robinson,et al.  Mortality in alcoholics with autonomic neuropathy. , 1988, Journal of neurology, neurosurgery, and psychiatry.

[25]  H. Vapaatalo,et al.  A survey of sudden death associated with the use of antipsychotic or antidepressant drugs: 49 cases in Finland , 1991, Acta psychiatrica Scandinavica.

[26]  B. Müller-Oerlinghausen,et al.  Tricyclic neuroleptic and antidepressant overdose: epidemiological, electrocardiographic, and clinical features--a survey of 92 cases. , 1990, Pharmacopsychiatry.

[27]  J. Morganroth,et al.  Variability of the QT measurement in healthy men, with implications for selection of an abnormal QT value to predict drug toxicity and proarrhythmia. , 1991, The American journal of cardiology.

[28]  K. Chergui,et al.  Neurochemical characteristics of amisulpride, an atypical dopamine D2/D3 receptor antagonist with both presynaptic and limbic selectivity. , 1997, The Journal of pharmacology and experimental therapeutics.

[29]  D J van Veldhuisen,et al.  Prognostic value of heart rate variability in chronic congestive heart failure secondary to idiopathic or ischemic dilated cardiomyopathy. , 1997, The American journal of cardiology.

[30]  R. Cohen,et al.  An Efficient Algorithm for Spectral Analysis of Heart Rate Variability , 1986, IEEE Transactions on Biomedical Engineering.

[31]  T. Barnes,et al.  Electrocardiographic changes in patients receiving neuroleptic medication , 1996, Acta psychiatrica Scandinavica.