From the Guidelines
For patients with prolonged QTc interval, the safest antipsychotics to use are aripiprazole (Abilify), olanzapine, and risperidone, 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. When treating a patient with prolonged QTc, it's essential to obtain baseline ECG measurements and monitor QTc regularly during treatment, especially when titrating doses, as recommended by 1. The following antipsychotics should be avoided in patients with prolonged QTc:
- Ziprasidone, due to its significant QTc prolongation effect of 5-22 ms, as reported in 1
- Thioridazine, which has a QTc prolongation effect of 25-30 ms and carries a black box warning for QTc prolongation, as mentioned in 1
- High-dose intravenous haloperidol, which has been associated with deaths and carries a non-black box warning, as noted in 1 The mechanism behind QTc prolongation involves blockade of hERG potassium channels, which delays cardiac repolarization. Some key points to consider when treating patients with prolonged QTc interval include:
- Avoiding concomitant treatment with more than one drug that can prolong the QT interval, as recommended by 1
- Assessing cardiac risk before initiation of treatment and evaluating the QT interval before and during treatment, as suggested by 1
- Optimizing cardiac risk factors and considering referral to a cardiologist if necessary, as proposed by 1
- Being cautious when treating elderly patients, as recommended 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. However, the QT effect was not systematically evaluated in a thorough QT study. 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)
- Quetiapine 2 is not the best option for patients with prolonged QTc due to the potential risk of further prolongation when combined with other medications.
- Clozapine 3 also has a warning for QT interval prolongation and should be used with caution when administering concomitant medications that prolong the QT interval.
- The best antipsychotics to use in patients with prolonged QTc are not explicitly stated in the provided drug labels.
- It is recommended to avoid using antipsychotics that are known to prolong the QTc interval, such as ziprasidone, chlorpromazine, and thioridazine.
From the Research
Antipsychotics and QTc Prolongation
- The risk of QTc prolongation varies among different antipsychotics, with some being more likely to cause this adverse reaction than others 4, 5.
- Studies have shown that lurasidone, aripiprazole, and brexpiprazole are associated with a lower risk of QTc prolongation, while sertindole, amisulpride, and ziprasidone are associated with a higher risk 4, 5.
- First-generation antipsychotics have been found to have a greater risk of QTc prolongation compared to second-generation antipsychotics 4.
Specific Antipsychotics and QTc Prolongation
- Lurasidone has been shown to have a low risk of QTc prolongation, making it a potential option for patients with prolonged QTc 4, 5.
- Aripiprazole and brexpiprazole have also been found to have a low risk of QTc prolongation, and may be suitable alternatives for patients with prolonged QTc 5.
- Ziprasidone, on the other hand, has been associated with a higher risk of QTc prolongation, and its use should be approached with caution, especially when combined with other medications that may interact with it 6, 7, 8.
- Sertindole and amisulpride have also been found to have a higher risk of QTc prolongation, and their use should be carefully considered in patients with prolonged QTc 4.
Combination Therapy and QTc Prolongation
- Combining certain antipsychotics, such as ziprasidone and quetiapine, may increase the risk of QTc prolongation due to pharmacokinetic interactions 7.
- Caution should be exercised when using ziprasidone with other medications that may interact with it, particularly those that inhibit the CYP3A4 enzyme 7, 8.