From the Guidelines
Aripiprazole is the recommended antipsychotic with the least QTc prolongation effect, with a mean QT prolongation of 0 ms, making it the safest option for patients with cardiac concerns. When considering antipsychotic medications, it's crucial to prioritize those with minimal QTc prolongation effects to reduce the risk of cardiac complications. According to the study 1, antipsychotics like aripiprazole, olanzapine, and risperidone have minimal QTc prolongation effects, with mean QT prolongations of 0 ms, 2 ms, and 0-5 ms, respectively.
Key Considerations
- Aripiprazole's partial agonist mechanism at D2 receptors contributes to its safer cardiac profile, with fewer side effects compared to other antipsychotics.
- Lurasidone is another option with minimal QTc impact, although its starting dose and administration requirements may differ from aripiprazole.
- Baseline ECG measurements and periodic monitoring of QTc intervals are essential, especially in patients with pre-existing cardiac conditions or those taking other QTc-prolonging medications.
- Drug interactions and electrolyte deficiencies, particularly potassium and magnesium, can exacerbate QTc prolongation and should be carefully managed.
QTc Prolongation Risks
- Antipsychotics with high affinity for potassium channels, such as thioridazine, pose a greater risk of QTc prolongation.
- The mechanism behind QTc prolongation involves blockade of potassium channels in cardiac tissue, delaying ventricular repolarization.
- Patients with cardiac concerns should be closely monitored, and alternative antipsychotics with lower QTc prolongation risks should be considered.
From the FDA Drug Label
The effects of lurasidone hydrochloride tablets on the QTc interval were evaluated in a randomized, double-blind, multiple-dose, parallel-dedicated thorough QT study in 43 patients with another indication, who were treated with lurasidone hydrochloride tablets doses of 120 mg daily, 600 mg daily and completed the study The maximum mean (upper 1-sided, 95% CI) increase in baseline- adjusted QTc intervals based on individual correction method (QTcI) was 7.5 (11.7) ms and 4.6 (9. 5) ms, for the 120 mg and 600 mg dose groups respectively, observed at 2 to 4 hours after dosing.
- QTc interval increase: The maximum mean increase in QTc intervals was 7.5 ms and 4.6 ms for the 120 mg and 600 mg dose groups, respectively.
- QTc sparing: Lurasidone hydrochloride tablets have a minimal effect on the QTc interval, suggesting that it is a QTc sparing antipsychotic 2.
From the Research
QTC Sparing Antipsychotic
- Antipsychotic medications can prolong the QTc interval, increasing the risk of potentially fatal ventricular arrhythmias 3.
- Some antipsychotics, such as iloperidone and ziprasidone, are more likely to cause QTc prolongation, while others like aripiprazole and lurasidone appear to have minimal risk 3, 4.
- Factors that increase the risk of QTc prolongation include genetic vulnerabilities, female sex, older age, pre-existing cardiovascular disease, electrolyte abnormalities, and non-psychiatric medications 3.
- A study found that sertindole had the highest risk of reporting QT prolongation, followed by ziprasidone and amisulpride, while lurasidone was associated with the lowest risk 4.
- Another study suggested that aripiprazole, brexpiprazole, and olanzapine do not increase QT interval, while ziprasidone, risperidone, and quetiapine are associated with QT prolongation and greater odds of torsades de pointes ventricular tachycardia 5.
- Aripiprazole's cardiac safety has been assessed, and it is considered a low-risk antipsychotic regarding cardiac safety in healthy patients, but baseline and steady-state electrocardiogram is recommended in patients at high risk for torsade 6.
- Routine ECG monitoring is not mandatory for patients receiving antipsychotics without cardiac risk factors, but it is useful when administering antipsychotic medications in the presence of co-existing risk factors 7.