What are the best antipsychotics for patients with prolonged QTc (QT interval corrected) interval?

From the Guidelines

For patients with prolonged QTc interval, the safest antipsychotics are aripiprazole (Abilify) and olanzapine, as they have minimal effects on cardiac repolarization and are less likely to further prolong the QTc interval, as shown in the study by 1. The study by 1 provides a comparison of the QT prolongation effects of different antipsychotics, with aripiprazole and olanzapine having the lowest risk of QT prolongation. Some key points to consider when prescribing antipsychotics to patients with QTc concerns include:

• Obtaining a baseline ECG and electrolytes, as hypokalemia, hypomagnesemia, and hypocalcemia can worsen QTc prolongation, as recommended by 1
• Avoiding ziprasidone, iloperidone, quetiapine, and thioridazine, which have higher risks of QTc prolongation, as noted in the study by 1
• Considering cardiology consultation for patients requiring antipsychotics who already have QTc >500 ms, as suggested by 1
• Regular ECG monitoring is recommended when using any antipsychotic in patients with cardiac risk factors, as advised by 1 The mechanism behind QTc prolongation involves blockade of hERG potassium channels, which delays cardiac repolarization and increases the risk of torsades de pointes, a potentially fatal arrhythmia, as explained in the study by 1. It is essential to weigh the benefits and risks of antipsychotic treatment in patients with QTc concerns and to closely monitor their cardiac health, as recommended by 1. In terms of specific antipsychotics, the study by 1 provides the following information:
• Aripiprazole: 0 ms QT prolongation
• Olanzapine: 2 ms QT prolongation
• Quetiapine: 6 ms QT prolongation
• Ziprasidone: 5-22 ms QT prolongation
• Thioridazine: 25-30 ms QT prolongation Overall, aripiprazole and olanzapine are the safest options for patients with prolonged QTc interval, due to their minimal effects on cardiac repolarization, as shown in the study by 1.

From the FDA Drug Label

5.12 QT Prolongation In clinical trials, quetiapine was not associated with a persistent increase in QT intervals. The use of quetiapine should be avoided in combination with other drugs that are known to prolong QTc including Class 1A antiarrythmics (e.g., quinidine, procainamide) or Class III antiarrythmics (e.g., amiodarone, sotalol), antipsychotic medications (e.g., ziprasidone, chlorpromazine, thioridazine), antibiotics (e.g., gatifloxacin, moxifloxacin), or any other class of medications known to prolong the QTc interval (e.g., pentamidine, levomethadyl acetate, methadone)

The best antipsychotics for patients with prolonged QTc are not explicitly stated in the provided drug labels.

• Quetiapine should be avoided in combination with other drugs that are known to prolong QTc.
• Clozapine should be used with caution when administering concomitant medications that prolong the QT interval. It is essential to exercise caution when prescribing antipsychotics to patients with increased risk of QT prolongation, such as those with cardiovascular disease, family history of QT prolongation, or congestive heart failure 2 3.

From the Research

Antipsychotics and QTc Prolongation

• The risk of QTc interval prolongation is a concern when prescribing antipsychotics, as it can increase the risk of life-threatening arrhythmias 4, 5, 6.
• Studies have investigated the incidence of QTc interval prolongation among patients receiving antipsychotic treatment, with varying results:
  • Clozapine and olanzapine were associated with a greater increase in QTc interval compared to haloperidol 4.
  • Combination therapy with antipsychotics and antidepressants was found to cause significant QT prolongation, whereas monotherapy with an antipsychotic agent did not 5.
  • Olanzapine and quetiapine were found to have similar impacts on QTc prolongation in critically ill patients 7.
• Certain antipsychotics have been identified as having a higher risk of QT prolongation, including:
  • Sertindole, ziprasidone, and amisulpride, which were found to have the highest risk of reporting QT prolongation 6.
  • Risperidone and quetiapine, which were associated with QT prolongation and greater odds of torsades de pointes ventricular tachycardia, especially in cases of drug overdose 8.
• In contrast, some antipsychotics have been found to have a lower risk of QT prolongation, including:
  • Lurasidone, which was associated with the lowest risk of reporting QT prolongation 6.
  • Aripiprazole, brexpiprazole, and olanzapine, which were found to not increase QT interval or were associated with a lower risk of QT prolongation 8.

Recommendations for Antipsychotic Use

• Clinicians may recommend aripiprazole, brexpiprazole, or olanzapine in licensed doses to avoid QT prolongation and reduce the risk of ventricular tachycardia 8.
• Careful monitoring of the QT interval is suggested in patients taking combined treatment of antipsychotic and antidepressant agents 5.
• The risk of QT prolongation should be considered when prescribing antipsychotics, particularly in patients with pre-existing cardiac conditions or those taking other medications that may affect the QT interval 4, 6.