Cardiac arrest and ventricular arrhythmia in patients taking antipsychotic drugs: cohort study using administrative data

Hennessy, Sean; Bilker, Warren B.; Knauss, Jill; Margolis, David J.; Kimmel, Stephen E.; Reynolds, Robert F.; Glasser, Dale B.; Morrison, Mary F.; Strom, Brian L.

doi:10.1136/bmj.325.7372.1070

Cited by 241 publications

(178 citation statements)

References 15 publications

Supporting

Mentioning

156

Contrasting

Unclassified

Order By: Relevance

“…Case-control studies and epidemiological data show increased incidence of sudden cardiac death in psychiatric patients taking antipsychotics (Hennessy et al 2002). Other studies have revealed the potential of several phenothiazines to induce acquired L-QT syndrome, with prolonged QT c intervals and a high risk for both TdP and sudden cardiac death (Reilly et al 2000).…”

Section: Discussionmentioning

confidence: 99%

Effect of perphenazine on electrogram of rat isolated heart

et al. 2011

View full text Add to dashboard Cite

The aim of this study was to clarify whether administration of antipsychotic perphenazine contributes to the electrophysiological changes of the isolated heart. Fourteen adult male Wistar rats were divided into two groups. Langendorff hearts were perfused with Krebs-Henseleit solution at constant pressure (85 mmHg) and 37 °C (CaCl 2 , 1.2 mM). The electrogram was recorded by touch-free method. The hearts of the first group were exposed to 3.10 -5 M perphenazine, the hearts of the second group to 3.10 -8 M perphenazine. The incidence of arrhythmias and the heart rate and QT interval changes were studied on electrogram during 30 min periods of control, the first perphenazine administration, washout, and the second drug administration.Perphenazine administration significantly prolonged QT (p < 0.001) and QTc (p < 0.05) in group 1. In group 2, QT and QTc prolongation was less pronounced (p < 0.05). A number of arrhythmias appeared, from single premature ventricular complexes to more severe ones in both groups. The heart rate changes were non-significant.We conclude that although phenothiazines are still medicaments of choice in certain psychoses, their cardiovascular side effects should be always taken in consideration. Phenothiazines, Langendorff heart, QT-interval, arrhythmiaCardiovascular system disorders are among the most common causes of morbidity and mortality in developed countries. Many of them are caused by side effects of noncardiovascular drugs whose nature and mode of action vary greatly. A typical example is psychotropic drugs, substances with reported high incidence of cardiovascular side effects, often expressed as various electrophysiological changes. Their representative perphenazine has been used as a psychotropic drug for several decades in therapy of certain psychiatric disorders. It has been reported to induce asymptomatic ECG changes, tachyarrhythmias, self-terminating arrhythmias, or even ventricular fibrillation resulting in the cardiac arrest, especially when overdosed. There are no reports that perphenazine affects electrophysiological properties of the cardiac tissue at therapeutic doses, but, certain ECG changes were observed during its administration in the presence of other potentially arrhythmogenic factors (Magorien et al. 1979).In isolated cardiomyocytes, the effects of perphenazine is functionally related to a variety of ion membrane currents. It reversibly blocks fast sodium current I Na and transient outward potassium current I to . Sensitivity of I Na and I to to perphenazine lies in the micromolar range, whereas the therapeutic plasma concentrations are in the nanomolar range (Bébarová et al. 2009). In isolated rat hearts, perphenazine at concentrations highly above the clinically relevant range caused numerous ECG changes (Langslet 1970).Perphenazine-triggered cardiovascular side effects may be of various severities. Prolonged QT interval is supposed to be a marker for the drug arrhythmogenic capacity. Therefore, L-QT is of major concern; however, there is growing evid...

show abstract

Section: Discussionmentioning

confidence: 99%

Effect of perphenazine on electrogram of rat isolated heart

et al. 2011

View full text Add to dashboard Cite

show abstract

“…Clinical aspects of acute treatment with haloperidol and its impact on cardiovascular system, primarily QT interval prolongation and associated arrhythmias, were studied repeatedly (Metzger and Friedman 1993;Hennessy et al 2002;Beach et al 2013). Effects of the acute and/or chronic exposure to haloperidol have been also studied on various biomodels and species, including rat (Fialova et al 2009), guinea pig (Testai et al 2007;Fialova et al 2009), and rabbit (Dhein et al 2008).…”

Section: Discussionmentioning

confidence: 99%

Long-Term Haloperidol Treatment Prolongs QT Interval and Increases Expression of Sigma 1 and IP<sub>3</sub> Receptors in Guinea Pig Hearts

Stračina

Slaninová

Polanská

et al. 2015

Tohoku J. Exp. Med.

View full text Add to dashboard Cite

Haloperidol is a neuroleptic drug used for a medication of various psychoses and deliria. Its administration is frequently accompanied by cardiovascular side effects, expressed as QT interval prolongation and occurrence of even lethal arrhythmias. Despite these side effects, haloperidol is still prescribed in Europe in clinical practice. Haloperidol binds to sigma receptors that are coupled with inositol 1,4,5-trisphosphate (IP 3 ) receptors. Sigma receptors are expressed in various tissues, including heart muscle, and they modulate potassium channels. Together with IP 3 receptors, sigma receptors are also involved in calcium handling in various tissues. Therefore, the present work aimed to study the effects of long-term haloperidol administration on the cardiac function. Haloperidol (2 mg/kg once a day) or vehiculum was administered by intraperitoneal injection to guinea pigs for 21 consecutive days. We measured the responsiveness of the hearts isolated from the haloperidol-treated animals to additional application of haloperidol. Expression of the sigma 1 receptor and IP 3 receptors was studied by real time-PCR and immunohistochemical analyses. Haloperidol treatment caused the significant decrease in the relative heart rate and the prolongation of QT interval of the isolated hearts from the haloperidol-treated animals, compared to the hearts isolated from control animals. The expression of sigma 1 and IP 3 type 1 and type 2 receptors was increased in both atria of the haloperidol-treated animals but not in ventricles. The modulation of sigma 1 and IP 3 receptors may lead to altered calcium handling in cardiomyocytes and thus contribute to changed sensitivity of cardiac cells to arrhythmias.

show abstract

“…Most antipsychotics and some antidepressants may be associated with QTc prolongation (Glassman, 2005). Patients using AP have higher rates of cardiac arrest or ventricular arrhythmias than controls, with ratios ranging from 1.7 to 5.3 (Ray et al, 2001;Hennessy et al, 2002;Reilly et al, 2002). Antipsychotics associated with a greater risk of QTc prolongation include pimozide, thioridazine and mesoridazine among the FGAs (Vieweg, 2002;Reilly et al, 2002) and sertindole and ziprasidone among the SGAs (Thomas et al, 2010).…”

Section: Drugmentioning

confidence: 99%

The Impact of Cardiometabolic Risk in Patients with Severe Mental Illness: From Evidence to Clinical Management

Sciascio¹,

Calò²

2011

Psychiatric Disorders - Worldwide Advances

View full text Add to dashboard Cite

Cardiac arrest and ventricular arrhythmia in patients taking antipsychotic drugs: cohort study using administrative data

Abstract: Objective To examine the rates of cardiac arrest and ventricular arrhythmia in patients with treated schizophrenia and in non-schizophrenic controls.

Cited by 241 publications

References 15 publications

Effect of perphenazine on electrogram of rat isolated heart

Effect of perphenazine on electrogram of rat isolated heart

Long-Term Haloperidol Treatment Prolongs QT Interval and Increases Expression of Sigma 1 and IP<sub>3</sub> Receptors in Guinea Pig Hearts

The Impact of Cardiometabolic Risk in Patients with Severe Mental Illness: From Evidence to Clinical Management

Contact Info

Product

Resources

About