The potential cardiotoxicity of antipsychotic drugs as assessed by heart rate variability

Abstract

Most antipsychotic drugs have cardiac effects as a consequence of their pharmacological actions. Recently, thioridazine has been subjected to a restricted indications notice and sertindole had its license withdrawn because of concerns about their potential cardiotoxicity. In the development of new atypical agents, heart-rate corrected QT effects are evaluated but it is unclear how predictive these are of clinically significant cardiotoxicity or sudden death. Heart rate variability (HRV) is a potential index of cardiotoxicity which has been found to be decreased following antidepressants and clozapine. We studied acute HRV changes following antipsychotic agents. Sixteen healthy male volunteers received risperidone (4 mg), olanzapine (10 mg), thioridazine (50 mg) or placebo in a randomized cross-over design. Subjective effects and psychomotor function were assayed at 2 h and both linear (summary statistics) and non-linear (scatterplot) measures of HRV were evaluated by continuous electrocardiogram recording over 10 h. Differential effects of single doses of the three antipsychotic drugs on HRV were found, and these were independent of their sedative effects. Olanzapine increased, and thioridazine decreased HRV, while risperidone had no effect. HRV is sensitive to the acute effects of antipsychotics. It may prove to be a reliable index of their potential for cardiotoxicity. Further studies in both healthy volunteers and patients on antipsychotic medication will be valuable.

Autonomic Modulation and Health-Related Quality of Life among Schizophrenic Patients Treated with Non-Intensive Case Management

“…Although no correlation between cardiovagal function and antipsychotic use was identified, antipsychotic use may still exacerbate autonomic dysfunction [15], [16]. The impact of long-term antipsychotic use on autonomic modulation of chronic patients as well as its relationship with cardiac toxicity deserve further investigation [59]. Our results showed no association between the patient's functioning and lower measures of HRV, which were different from Fujibayashi et al 's findings [10].…”

Heart Rate Variability in Schizophrenic Patients Switched from Typical Antipsychotic Agents to Amisulpride and Olanzapine

“…Our results did not show any obvious increase in HRV in the olanzapine group, and the hypothesis of improvement of cardiac heart function was not supported by the results of our study. Another possible explanation is that co-medication with benzodiazepine (in 12 of 18 patients in the olanzapine group) may cause a reduction in central vagal tone [25] ; however, similar results were not obtained in another study [17] .…”

“…Another study reported that olanzapine increased HRV in healthy male volunteers and, in a short-term evaluation [17] , they concluded that olanzapine may improve cardiac heart function; however, we should treat this conclusion with caution, as single-dose short-term observations in healthy males may not provide evidence of a reliable index for use in schizophrenia patients. Our results did not show any obvious increase in HRV in the olanzapine group, and the hypothesis of improvement of cardiac heart function was not supported by the results of our study.…”

“…These results were mainly interpreted as being a consequence of the effects of the medication, such as the anticholinergic effects of clozapine [16] . Few reports have evaluated other atypical antipsychotic agents [15,17] , and those studies lacked a long period of evaluation. In this study, we monitored HRV changes every month in schizophrenia patients who switched from typical antipsychotic agents to atypical agents (amisulpride and olanzapine) throughout a 3-month follow-up.…”

Effects of antipsychotic drugs on cardiovascular variability in participants with bipolar disorder

“…The bulk of the existing literature examining antipsychotic drug effects on HRV has focused on samples with schizophrenia, and the results have been generally inconclusive with exposure variably defined (Bar et al , 2008a; Chang et al , 2010; Cohen et al , 2001; Hempel et al , 2009; Latalova et al , 2010; Malaspina et al , 2002; Mujica-Parodi et al , 2005; Silke et al , 2002; Wang et al , 2008). Several studies found a negative correlation between AP exposure and parasympathetic activity (Bar et al , 2008a; Mujica-Parodi et al , 2005).…”