The cardiac safety of aripiprazole treatment in patients at high risk for torsade: a systematic review with a meta-analytic approach

Abstract

Aripiprazole is a low-risk antipsychotic regarding cardiac safety in healthy patients. However, baseline and steady state electrocardiogram is recommended in patients at high risk for torsade due to marked QTc prolongation, absence of a TQT study, and lack of data in this group.

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

“…Even though aripiprazole is thought not to affect QTc interval (13,14) several cases of long QTc after aripiprazole treatment have been described (15,16). Furthermore, there is no "Thorough QT/QTc Study" (a study to determine if a drug can prolong QTc) of aripiprazole available in the literature.…”

An analysis of QTc prolongation with atypical antipsychotic medications and selective serotonin reuptake inhibitors using a large ECG record database

“…20 Therefore, QTc intervals using Fridericia's formula (QTcF) rather than QTcB are more reliable for investigation of QT prolongation with clozapine at HR > 70. 21 In these data, we found that the major result of clozapine regarding QTc prolongation risk was not changed by the correction methods. No significant effects on the QTc interval were found with the use of fluoxetine, paroxetine, or sertraline, which corresponds with results from previous studies.…”

The Prevalence and Significance of Antipsychotic Dosing on QTc Prolongation

“…There had been reports of sudden cardiac deaths associated with antipsychotics, particularly thioridazine, for years before sertindole, but this was the first FDA intervention in the matter. In vitro studies have shown the ability of antipsychotics to block the potassium rectifier channel (I Kr ) that is involved in the repolarization of the ventricles (Berling & Isbister, 2015;Fujii et al, 2014, Polcwiartek et al, 2015, Vieweg et al, 2013. However, in vitro studies have shown that despite risperidone's ability to inhibit this channel by 80% at the highest concentrations, it had minimal effect on cardiac conduction (Berling & Isbister, 2015;Vieweg et al, 2013).…”

“…Berling and Isbister demonstrated even in the situation of antipsychotic overdose prolongation of the QTc only occurred in 3-56% of patients depending on the antipsychotic and only one patient out of 494 developed TdP after an overdose of thioridazine (2015). Studies that did report TdP occurring in patients on antipsychotics found most, if not all, had at least one other risk factor present (Vieweg et al, 2014;Polcwiartek et al, 2015). Sudden cardiac death from TdP is also so rare in this population a five-year cross-sectional study calculated 3000 patients would need to be screened by ECG in order to prevent one death (Poncet et al, 2015).…”

“…This is measured via an electrocardiographic (ECG) machine and corrected for heart rate (QTc) as it shortens with increasing heart rates (Glassman & Brigger, 2001 a QTc ≥ 500 milliseconds (ms) or an increase ≥ 60 ms from baseline, in secondary, drug-induced, is considered clinically relevant for increasing the risk of ventricular arrhythmias, including torsade de points (Camm et al, 2012) In 1966 this term was developed to describe a malignant polymorphic ventricular arrhythmia characterized by a twisting pattern of the QRS complex and associated with syncope and sudden death (Glassman & Brigger 2001). Most episodes are transient and self-limited, but 1-20% can lead to sudden death (Berling & Isbister, 2015;Camm et al, 2012;Girardin et al, 2013;Polcwiartek et al, 2015). Since this term was coined in congenital long QT syndrome, it is still unclear if drugs that prolong the QTc interval behave similarly and carry the same risk for inducing torsade de pointes (Glassman & Brigger, 2001).…”