From the Guidelines
Aripiprazole, pregabalin, and fluoxetine can all potentially cause QTc prolongation, but to varying degrees, with fluoxetine carrying a moderate risk, aripiprazole having a lower risk, and pregabalin generally having minimal effect on QTc interval. According to the study by 1, aripiprazole has a mean QT prolongation of 0 ms, indicating a lower risk compared to other antipsychotics. On the other hand, fluoxetine has been associated with QTc prolongation, particularly at higher doses or in patients with pre-existing cardiac conditions, as noted in the study by 1. Pregabalin, as mentioned in the study by 1, can also contribute to QTc prolongation, especially when used in combination with other QT-prolonging medications.
When prescribing these medications, it's essential to:
- Obtain baseline ECGs in patients with risk factors such as electrolyte abnormalities, congenital long QT syndrome, heart failure, or concurrent use of other QT-prolonging drugs
- Regularly monitor ECGs in high-risk patients, particularly when using fluoxetine or aripiprazole
- Assess cardiac risk before initiation of treatment and during titration of dose, as recommended by 1
- Avoid concomitant treatment with more than one drug with the propensity of prolonging the QT interval, if possible, as suggested by 1
The mechanism behind QTc prolongation involves blockade of potassium channels in cardiac cells, which delays ventricular repolarization and can potentially lead to dangerous arrhythmias like Torsades de Pointes in severe cases. Therefore, it's crucial to carefully evaluate the risks and benefits of these medications and take necessary precautions to minimize the risk of QTc prolongation.
From the FDA Drug Label
ECG abnormalities (such as QT interval prolongation and ventricular tachycardia, including torsades de pointes–type arrhythmias)
- Fluoxetine can cause prolonged QTc as it has been reported to cause ECG abnormalities, including QT interval prolongation.
- There is no information about aripiprazole or pregabalin in the provided drug label. 2
From the Research
QT Interval Prolongation and Associated Drugs
- Aripiprazole has been studied in relation to QT interval prolongation, with low-quality evidence suggesting it does not increase QT interval 3, 4.
- Pregabalin is not mentioned in the provided studies as a potential cause of QT interval prolongation.
- Fluoxetine, an antidepressant, is not directly mentioned in the studies as a cause of QT interval prolongation, but the study 5 mentions that antidepressants can prolong the QT interval.
Risk Factors for QT Interval Prolongation
- Congenital long QT syndrome, clinically significant bradycardia or heart disease, electrolyte imbalance (especially hypokalaemia, hypomagnesaemia), impaired hepatic/renal function, and concomitant treatment with other drugs with known potential for pharmacokinetic/pharmacodynamic interactions are risk factors for QT interval prolongation 5.
- Polypharmacy can also contribute to QT interval prolongation, as seen in cases where multiple drugs with potential to prolong QT interval are used together 6.
Comparison of Antipsychotics and QT Interval Prolongation
- Aripiprazole is considered a low-risk antipsychotic regarding cardiac safety, with low-quality evidence suggesting it does not increase QT interval 3, 4.
- Other antipsychotics, such as sertindole, ziprasidone, and amisulpride, have been associated with a higher risk of QT prolongation 7.
- Lurasidone is associated with the lowest risk of QT prolongation reporting 7.