Can Seroquel (quetiapine) cause QT interval prolongation?

Quetiapine and QT Interval Prolongation

Yes, quetiapine (Seroquel) can cause QT interval prolongation, though the risk is lower compared to some other antipsychotics and is primarily dose-dependent with higher risk in overdose situations.

Risk Assessment and Evidence

Quetiapine has been associated with QT prolongation, though the FDA label indicates that in clinical trials, quetiapine was not associated with a persistent increase in QT intervals 1. However, post-marketing experience has reported cases of QT prolongation, particularly in:

• Overdose situations
• Patients with concomitant illnesses
• Patients taking other medications known to cause electrolyte imbalance or increase QT interval

The risk appears to be dose-dependent:

• In standard therapeutic doses, the risk is relatively low (approximately 5% of overdoses showed abnormal QT intervals) 2
• The risk increases significantly in overdose situations 3

Monitoring and Management Recommendations

When to Monitor

• Baseline ECG before initiating treatment 4
• Follow-up ECG during dose titration 4
• Additional monitoring for high-risk patients

High-Risk Patients

Caution should be exercised when prescribing quetiapine to patients with:

• Pre-existing cardiac disease
• Family history of QT prolongation
• Congestive heart failure
• Heart hypertrophy
• Elderly patients
• Electrolyte abnormalities (particularly hypokalemia and hypomagnesemia)
• Concomitant use of other QT-prolonging medications 1

When to Discontinue or Reduce Dose

Treatment should be stopped or dose reduced if:

• QT interval or QTc reaches >500 ms
• QT interval increases by >60 ms compared to baseline 4

Risk Mitigation Strategies

1. Avoid drug interactions: Avoid combining quetiapine with other medications known to prolong QT interval, including:

   • Class 1A antiarrhythmics (quinidine, procainamide)
   • Class III antiarrhythmics (amiodarone, sotalol)
   • Other antipsychotics (ziprasidone, chlorpromazine, thioridazine)
   • Certain antibiotics (gatifloxacin, moxifloxacin)
   • Other QT-prolonging medications 1

2. Maintain electrolyte balance: Prevent and correct hypokalemia and hypomagnesemia 4

3. Consider alternatives: For patients with multiple risk factors, consider antipsychotics with lower QT prolongation risk such as aripiprazole, brexpiprazole, or olanzapine 5

Clinical Perspective

When comparing quetiapine to other antipsychotics:

• Lower risk than thioridazine, amisulpride, and ziprasidone
• Similar or slightly lower risk than risperidone
• Higher risk than aripiprazole, brexpiprazole, and olanzapine 5

Important Caveats

1. QT prolongation with quetiapine is often associated with tachycardia and may not be dose-dependent at therapeutic doses, suggesting lower risk of torsade de pointes compared to some other antipsychotics 2

2. Critically ill patients and those in intensive care settings are at particularly high risk for QT prolongation due to multiple risk factors and medication interactions 6

3. Even non-massive overdoses of quetiapine can cause considerable QT prolongation, especially when combined with other psychotropic medications like risperidone 3

Remember that QT prolongation is a surrogate marker for the more serious but rare complication of torsade de pointes, which can lead to sudden cardiac death. The clinical decision to use quetiapine should balance psychiatric benefits against cardiovascular risks.