What is the risk of a male patient with ectopic beats and prolonged QTc interval (470 milliseconds) on antipsychotic medications (e.g., quetiapine) developing arrhythmia, specifically Torsades de Pointes, and what is the management plan for him?

From the Guidelines

This patient is at moderate risk for developing arrhythmias including Torsades de Pointes due to his prolonged QTc interval (470 ms), presence of ectopic beats, and use of antipsychotics which can further prolong QT interval. Management should focus on QT interval monitoring and medication adjustment. First, consider switching to an antipsychotic with lower QT-prolonging potential such as aripiprazole, brexpiprazole, or lurasidone, as suggested by the study 1. Some key points to consider in management include:

• Obtain baseline and follow-up ECGs after any medication changes.
• Correct any electrolyte abnormalities, particularly potassium (maintain >4.0 mEq/L) and magnesium (>2.0 mg/dL), as electrolyte imbalances can increase the risk of torsades de pointes 1.
• Avoid adding other QT-prolonging medications.
• If antipsychotic change isn't possible, reduce the dose to the minimum effective level.
• For patients with QTc >500 ms or significant increase from baseline, immediate cardiology consultation is warranted. Regular ECG monitoring should occur every 3-6 months while on QT-prolonging antipsychotics, as recommended by guidelines 1. These interventions are critical because QT prolongation increases risk of Torsades de Pointes, a potentially fatal ventricular arrhythmia, with risk increasing substantially when QTc exceeds 500 ms, especially in the presence of ectopic beats which may trigger the arrhythmia. Intravenous magnesium can suppress episodes of torsades de pointes without necessarily shortening QT, even when serum magnesium is normal, and temporary pacing is highly effective in managing torsades de pointes that is recurrent after potassium and magnesium supplementation 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. In post marketing experience, there were cases reported of QT prolongation in patients who overdosed on quetiapine [see OVERDOSAGE (10. 1)] , in patients with concomitant illness, and in patients taking medicines known to cause electrolyte imbalance or increase QT interval [see DRUG INTERACTIONS (7.1)] . 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 should also be avoided in circumstances that may increase the risk of occurrence of torsade de pointes and/or sudden death including (1) a history of cardiac arrhythmias such as bradycardia; (2) hypokalemia or hypomagnesemia; (3) concomitant use of other drugs that prolong the QTc interval; and (4) presence of congenital prolongation of the QT interval Caution should also be exercised when quetiapine is prescribed in patients with increased risk of QT prolongation (e.g., cardiovascular disease, family history of QT prolongation, the elderly, congestive heart failure, and heart hypertrophy).

The patient has a high risk of developing arrhythmia and torsades due to the following factors:

• Prolonged QTc interval of 470
• Ectopics
• Antipsychotic medication use A management plan for this patient should include:
• Close monitoring of the patient's QTc interval and cardiac function
• Avoidance of other medications that may prolong the QTc interval
• Correction of electrolyte imbalances such as hypokalemia or hypomagnesemia
• Consideration of alternative antipsychotic medications that do not prolong the QTc interval 2

From the Research

Risk of Arrhythmia and Torsades

• The patient's QTc interval of 470 ms is considered prolonged, which increases the risk of arrhythmias and torsades de pointes (TdP) 3, 4.
• Antipsychotic medications, particularly first-generation antipsychotics such as haloperidol and thioridazine, have been associated with QTc prolongation and an increased risk of TdP 3, 4.
• The risk of TdP and sudden death associated with antipsychotics is generally low, but it can be increased by factors such as female gender, older age, pre-existing cardiovascular disease, electrolyte abnormalities, and non-psychiatric medications 4, 5.

Management Plan

• Regular ECG monitoring is recommended to assess the patient's QTc interval and detect any potential arrhythmias 6, 5.
• The choice of antipsychotic medication should be carefully considered, taking into account the patient's risk factors for QTc prolongation and the potential for the medication to cause QTc prolongation 3, 4, 7.
• Medications such as aripiprazole, brexpiprazole, and olanzapine may be recommended as they have been shown to have a lower risk of QTc prolongation compared to other antipsychotics 7.
• If substantial QTc prolongation (e.g., QTc > 500 ms) is present, a change in pharmacologic treatment may be considered, although the risks and benefits of discontinuing the medication should be carefully weighed 6.