Does Quetiapine (Seroquel) cause prolonged QTc interval?

From the Guidelines

Yes, Seroquel (quetiapine) can cause prolonged QTc interval, with a mean QT prolongation of 6 ms, as reported in a study published in 2016 1. This antipsychotic medication has been associated with QTc prolongation, though the risk is generally considered moderate compared to some other antipsychotics. The risk increases with higher doses, particularly above 500mg daily, and is more pronounced in elderly patients, those with pre-existing cardiac conditions, or patients taking other medications that also prolong QTc. Some key points to consider include:

• The risk is dose-dependent, with higher doses carrying greater risk.
• This effect occurs because quetiapine can block potassium channels in cardiac cells, delaying ventricular repolarization.
• Patients taking Seroquel should be monitored with baseline and follow-up ECGs, especially those with risk factors such as congenital long QT syndrome, heart disease, electrolyte abnormalities, or concurrent use of other QT-prolonging medications.
• Symptoms of concerning QT prolongation may include dizziness, palpitations, or syncope, which should prompt immediate medical attention. It is also worth noting that other studies have reported similar findings, including a study published in 2015 that listed quetiapine as a medication that can prolong the QT interval 1, and another study published in 2018 that mentioned quetiapine as a medication that may have a role in the management of delirium symptoms, but also noted its potential to prolong the QTc interval 1. However, the most recent and highest quality study, published in 2016, provides the most accurate estimate of the risk of QT prolongation associated with quetiapine 1.

From the FDA Drug Label

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).

Seroquel (quetiapine) may cause QTc prolongation in certain circumstances, such as overdose, concomitant illness, or use with other medications that prolong the QTc interval. However, it was not associated with a persistent increase in QT intervals in clinical trials.

• Key risk factors for QTc prolongation include:
  • Concomitant use of other drugs that prolong the QTc interval
  • History of cardiac arrhythmias
  • Hypokalemia or hypomagnesemia
  • Presence of congenital prolongation of the QT interval
  • Increased risk of QT prolongation (e.g., cardiovascular disease, family history of QT prolongation, the elderly, congestive heart failure, and heart hypertrophy) 2

From the Research

Seroquel and QTc Prolongation

• Seroquel, also known as quetiapine, has been associated with QTc interval prolongation, particularly in cases of overdose 3.
• A study published in 2001 reported a case of asymptomatic QTc prolongation in a patient who ingested a 2000-mg overdose of quetiapine fumarate, with a QTc interval of 537 ms 3.
• However, it is essential to note that the risk of QTc interval prolongation and torsade de pointes (TdP) associated with antipsychotics, including seroquel, is generally considered low 4.

Comparison with Other Antipsychotics

• A study comparing the effects of olanzapine and risperidone on QTc interval found that olanzapine was associated with QTc shortening, while risperidone was associated with QTc prolongation 5.
• Another study found that combination therapy with antipsychotics and antidepressants, including quetiapine, was associated with a significant increase in QTc interval, while monotherapy with antipsychotics did not result in significant QTc prolongation 6.

Monitoring and Risk Factors

• The risk of QTc interval prolongation and TdP is increased in patients with certain risk factors, such as female sex, older age, heart disease, hypokalemia, and use of other QTc-prolonging medications 7, 4.
• Electrocardiogram (ECG) monitoring is recommended for patients with these risk factors, as well as for those taking antipsychotics with a known risk of QTc prolongation 4.