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

Abstract

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.

Autonomic nervous system dysfunction in psychiatric disorders and the impact of psychotropic medications: a systematic review and meta-analysis

“…Duplicates were removed, titles and abstracts scanned, potential articles read and evaluated against inclusion criteria and authors contacted for additional data when necessary. In total, 140 case-control and 30 treatment 76,83,93,110,116,129,138,141,155,175,[187][188][189][190][191][192][193][194][195][196][197][198][199][200][201][202][203][204][205][206] studies were eligible for inclusion in the quantitative synthesis (151 case-control and 43 effect sizes for analysis); 10 of the studies were included in both the case-control and treatment analyses. 76,83,93,110,116,129,138,141,155,175 Four subgroups of disorders (mood, anxiety-related, psychotic and substance dependence disorders) and 2 classes of psychotropic medications (antidepressants and antipsychotics) were included.…”

“…221 There are a number of direct and indirect mechanisms by which second-generation antipsychotic drugs like clozapine may alter HRV, particularly by direct blockade of adrenergic and cholinergic receptors on the heart and blood vessels, but also indirectly though baroreflex receptors and through known metabolic sideeffects, such as weight gain. 222 However, it has also been argued by some that antipsychotic-induced reductions in HRV indicate autonomic imbalance, 202,223 reflecting greater sympathetic and reduced vagal influence over the heart. While increased cardiovascular mortality in psychotic disorders has been attributed to modifiable lifestyle factors, 209 such as higher rates of smoking, lack of exercise and substance misuse, the present meta-analysis suggests that autonomic dysfunction exists even in medication-free individuals and that some psychotropics may further exacerbate cardiac risk in these individuals.…”

Cardiac side effects of psychiatric drugs

“…The advent of increasing regulatory control and post-marketing drug surveillance has resulted in betterquality studies assessing the effect of antipsychotic drugs, particularly the newer atypical agents, on cardiac function. Sertindole has a clear association with QT prolongation (Agelink et al, 2001), and there appears to be a dose-related effect of risperidone (Tran et al, 1997) and clozapine (Kang et al, 2000). Olanzapine (Czekalla et al, 2001) and quetiapine (Small et al, 1997) appear not to have significant effects on cardiac electrophysiology in clinical studies, and data for amisulpiride are too few to draw any meaningful conclusions.…”

Heart Rate Variability and Metabolic Syndrome in Hospitalized Patients with Schizophrenia

“…These medicines may have affected autonomic nervous system as a mediating factor between metabolic syndrome and HRV in these patients. Agelink et al (2001) suggested neurocardiac effects of atypical neuroleptics (amisulpride, olanzapine, clozapine and sertindole) on ANF should exert distinct effects on ANF depending on the extent to which anticholinergic and/or antiadrenergic effects. In this study, S participants were on various antipsychotic drugs.…”

“…We cannot rule out potential effects of antipsychotic drugs or schizophrenic symptoms because the metabolic syndrome may be associated with HRV differently in inpatients with schizophrenia due to antipsychotic polypharmacy (Agelink et al, 2001).…”