What are the risks of QTc (QT interval corrected) prolongation and bradycardia with Abilify (aripiprazole)?

From the Guidelines

Abilify (aripiprazole) has a low risk of causing QTc prolongation and bradycardia compared to other antipsychotic medications, with a mean QT prolongation of 0 ms, as reported in a study published in Pediatrics 1.

Key Points to Consider

• The risk of QTc prolongation with aripiprazole is generally minimal and not clinically significant in most patients.
• However, caution should be exercised in patients with pre-existing cardiac conditions, electrolyte abnormalities (particularly hypokalemia or hypomagnesemia), or in those taking other medications known to prolong the QT interval.
• Patients with congenital long QT syndrome or a history of significant cardiac arrhythmias should use aripiprazole with caution.
• The standard dosing of aripiprazole (typically 10-30 mg daily for adults) does not usually require routine ECG monitoring in otherwise healthy individuals, but baseline and follow-up ECGs may be appropriate for high-risk patients.

Clinical Management

• Assessment of cardiac risk is needed before initiation of treatment with aripiprazole, especially in elderly patients or those with structural heart disease 1.
• The QT interval should be evaluated before initiation of treatment and during titration of dose, and hypokalaemia should be avoided during treatment with aripiprazole 1.
• Concomitant treatment with more than one drug with the propensity of prolonging the QT interval should be avoided if possible, and cardiac risk factors should be optimized and/or a drug with a more favourable risk profile should be preferred if possible in the clinical situation 1.

Mechanism of Action

• The relatively favorable cardiac safety profile of aripiprazole is due to its unique mechanism of action as a partial dopamine agonist rather than a full antagonist, which results in fewer cardiovascular side effects compared to typical antipsychotics.
• Aripiprazole's mechanism of action may contribute to its lower risk of QTc prolongation and bradycardia compared to other antipsychotic medications, as reported in a study published in the European Heart Journal 1.

From the FDA Drug Label

Common adverse reactions (reported in at least 5% of all overdose cases) reported with oral aripiprazole overdosage (alone or in combination with other substances) include vomiting, somnolence, and tremor Other clinically important signs and symptoms observed in one or more patients with aripiprazole overdoses (alone or with other substances) include acidosis, aggression, aspartate aminotransferase increased, atrial fibrillation, bradycardia, coma, confusional state, convulsion, blood creatine phosphokinase increased, depressed level of consciousness, hypertension, hypokalemia, hypotension, lethargy, loss of consciousness, QRS complex prolonged, QT prolonged, pneumonia aspiration, respiratory arrest, status epilepticus, and tachycardia. An electrocardiogram should be obtained in case of overdosage and if QT interval prolongation is present, cardiac monitoring should be instituted

The risks of QTc prolongation and bradycardia with Abilify (aripiprazole) include:

• QTc prolongation has been observed in patients with aripiprazole overdoses
• Bradycardia has been reported as a clinically important sign and symptom in patients with aripiprazole overdoses In case of overdosage, an electrocardiogram should be obtained and if QT interval prolongation is present, cardiac monitoring should be instituted 2

From the Research

Risks of QTc Prolongation and Bradycardia with Abilify (Aripiprazole)

• The risk of QTc interval prolongation with antipsychotic medications, including Abilify, is associated with an increased risk of torsade de pointes (TdP) and sudden cardiac death 3.
• Studies have identified several risk factors for QTc interval prolongation, including hypokalemia, female sex, drug-drug interactions, advancing age, genetic predisposition, hypomagnesemia, heart failure, and bradycardia 4, 5.
• Aripiprazole, the active ingredient in Abilify, has been found to have a low risk of QTc interval prolongation and torsadogenicity compared to other antipsychotics 6.
• A study in children with pervasive developmental disorders found no significant differences in QTc intervals after treatment with aripiprazole, and no post-treatment QTc exceeded 440 ms 7.
• However, it is still recommended to perform baseline and steady-state electrocardiogram monitoring in patients at high risk for torsade due to marked QTc prolongation, absence of a thorough QT study, and lack of data in this group 6.
• Bradycardia is also a risk factor for QTc interval prolongation, and patients with Abilify-induced bradycardia should be closely monitored for QTc prolongation and other cardiac complications 4, 5.

Monitoring and Prevention

• Regular monitoring of electrocardiography (EKG) and electrolytes is necessary to prevent TdP in patients at risk for QTc interval prolongation 4.
• Patients at risk for QTc interval prolongation should be educated to seek immediate medical attention if they experience symptoms such as palpitations, lightheadedness, dizziness, or syncope 4.
• Dose reduction or discontinuation of the offending drug, as well as correction of electrolyte imbalances, may be necessary to prevent QTc interval prolongation and TdP 4.