Antipsychotic drugs and QT prolongation

Abstract

Antipsychotic drugs (AD) are effective and frequently prescribed to more females than males. AD may cause serious cardiovascular side-effects, including prolonged QT interval, eventually leading to torsades de pointes (TdP) and sudden death. Epidemiologic data and case-control studies indicate an increased rate of sudden death in psychiatric patients taking AD. This review summarizes current knowledge about the QT prolonging effects of AD and gives practical suggestions. Amisulpride, clozapine, flupenthixol, fluphenazine, haloperidol, melperone, olanzapine, perphenazine, pimozide, quetiapine, risperidone, sulpiride, thioridazine and ziprasidone cause a QT prolongation ranging from 4 ms for risperidone to 30 ms for thioridazine. Our knowledge about the QT-prolonging effects of many AD is still limited. Females are under-represented in most studies. Many studies were conducted or supported by pharmaceutical companies. To avoid prodysrhythmia caused by QT prolongation, other factors influencing QT interval have to be considered, such as other drugs affecting the same pathway, hypokalemia, hypomagnesemia, bradycardia, increased age, female sex, congestive heart failure and polymorphisms of genes coding ion channels or enzymes involved in drug metabolism. Because the response of a patient to AD is individual, an electrocardiogram recording the QT interval has to be performed at baseline, after AD introduction and after occurrence of any factor that might influence the QT interval.

Evaluation of the Relationship Between Pharmacokinetics and the Safety of Aripiprazole and Its Cardiovascular Effects in Healthy Volunteers

“…Many studies have reported the effect of antipsychotics on QTc prolongation (37,38), being the most common thioridazine (withdrawn from the Spanish market in 2005) and ziprasidone (39). The effect of aripiprazole on the QTc interval in electrocardiograms remains unclear.…”

Incidence and outcomes of long QTc in acute medical admissions

“…Use of fluoroquinolones, which have been a cause for concern to their risk for TdP,30 are not promoted as first line 29. Safety issues have also been raised for use of QTc‐prolonging anti‐psychotic medications 2, 31. Such drugs are frequently used in‐hospital inpatients as delirium can affect a fifth of acute medical admissions 32.…”

Response of IKrand hERG Currents to the Antipsychotics Tiapride and Sulpiride

“…These drugs share an ability to block the rapid component of the delayed rectifier K ＋ current (IKr), resulting in a delayed repolarization of the cardiac action potential and prolongation of the QT interval, possibly leading to torsades de pointes [1]. Several epidemiological studies and case-control reports have shown that the rate of sudden death is increased in psychiatric patients taking antipsychotic drugs [2][3][4][5].…”

“…Antipsychotic drugs have been known to cause serious cardiovascular side-effects, including myocarditis, cardiomyopathy and abnormal cardiac rhythm [1]. These drugs share an ability to block the rapid component of the delayed rectifier K ＋ current (IKr), resulting in a delayed repolarization of the cardiac action potential and prolongation of the QT interval, possibly leading to torsades de pointes [1].…”

“…Overdose of sulpiride can cause sinus tachycardia, hypotension, arrhythmia and CNS depression [8]. Tiapride and sulpiride have been reported to induce cardiac ECG changes including prolongation of the corrected QT interval (QTc) and torsades de pointes at therapeutic doses [1,[9][10][11][12]. It is known that IKr -mediated by an ion channel encoded by the human ether-a-go-go-related gene (hERG) -is important for the termination of the cardiac action potential and determines the shape of the repolarization phase [13].…”