Is quetiapine (antipsychotic medication) a pro-arrhythmic drug?

Quetiapine is a Pro-Arrhythmic Drug with QT Prolongation Risk

Yes, quetiapine is a pro-arrhythmic drug that can cause QT prolongation and increase the risk of torsade de pointes and sudden cardiac death, particularly in high-risk patients. 1, 2

QT Prolongation Risk

• Quetiapine has been associated with QT prolongation in post-marketing experience, particularly in cases of overdose, in patients with concomitant illness, and in those taking other medications known to cause electrolyte imbalance or increase QT interval 2
• Among antipsychotics, quetiapine has a moderate QT-prolonging effect, following thioridazine and ziprasidone in severity but more concerning than aripiprazole 1
• In a recent study, more than 13% of patients receiving quetiapine developed severe QT prolongation (QTc >500ms or increase >60ms from baseline), which was significantly associated with increased risks of ventricular arrhythmias and sudden cardiac death 3

Risk Factors for Quetiapine-Induced QT Prolongation

• High-risk patients include those who are female, aged >65 years, have underlying long QTc (>500 ms), electrolyte abnormalities, prior sudden cardiac death, or are using other QT-prolonging medications 1
• Additional risk factors include:
  • History of cardiac arrhythmias such as bradycardia
  • Hypokalemia or hypomagnesemia
  • Concomitant use of other drugs that prolong the QTc interval
  • Presence of congenital prolongation of the QT interval
  • Cardiovascular disease, heart failure, and heart hypertrophy 2

Clinical Recommendations

• The FDA label explicitly states that quetiapine should be avoided in combination with other drugs known to prolong QTc, including Class 1A antiarrhythmics, Class III antiarrhythmics, other antipsychotics, certain antibiotics, or any other medications known to prolong the QTc interval 2
• Quetiapine should be avoided in circumstances that may increase the risk of torsade de pointes and/or sudden cardiac death 2
• If an antipsychotic is needed in patients with ventricular arrhythmias or at high risk for ventricular tachycardia, aripiprazole is favored as it has not been associated with QT prolongation or torsade de pointes 1
• ECG monitoring is advisable when initiating quetiapine in patients with risk factors for QT prolongation 3

Monitoring and Management

• Cardiovascular monitoring should include continuous electrocardiographic monitoring to detect possible arrhythmias, particularly in cases of overdose 2
• If antiarrhythmic therapy is needed, be aware that disopyramide, procainamide, and quinidine carry a theoretical hazard of additive QT-prolonging effects when administered in patients taking quetiapine 2
• In overdose situations, hypotension and circulatory collapse should be treated with appropriate measures such as intravenous fluids and/or sympathomimetic agents (note that epinephrine and dopamine should not be used due to beta stimulation potentially worsening hypotension in the setting of quetiapine-induced alpha blockade) 2

Comparative Risk Among Antipsychotics

• Among antipsychotics, thioridazine and ziprasidone have the most significant QTc-prolonging effect, followed by quetiapine, risperidone, and haloperidol 1
• Aripiprazole has not been associated with QT prolongation or torsade de pointes and is the safest option for patients at risk of arrhythmias 1, 4
• A meta-analysis found that ziprasidone increases QT interval and rates of QT prolongation, while risperidone and quetiapine are associated with QT prolongation and greater odds of torsade de pointes, especially in overdose cases 5

In conclusion, clinicians should exercise caution when prescribing quetiapine, particularly in patients with risk factors for QT prolongation, and consider alternative antipsychotics with lower pro-arrhythmic potential when appropriate.