What antipsychotic (anti-psychotic) medications have a minimal effect on the QT (QT interval) interval?

Antipsychotics with Minimal Effect on QTc Interval

Aripiprazole and brexpiprazole are the antipsychotics with minimal to no effect on QTc interval and should be preferred when QTc prolongation is a concern. 1, 2

QTc Prolongation Risk by Antipsychotic Medication

Antipsychotics vary significantly in their effect on QTc interval. Based on the most recent evidence:

Minimal QTc Effect (0-2 ms)

• Aripiprazole: 0 ms mean QTc prolongation 1
• Brexpiprazole: No QTc prolongation at therapeutic doses 2, 3
• Olanzapine: 2 ms mean QTc prolongation 1

Low to Moderate QTc Effect (3-10 ms)

• Risperidone: 0-5 ms mean QTc prolongation 1
• Quetiapine: 6 ms mean QTc prolongation 1
• Haloperidol: 7 ms mean QTc prolongation (oral); higher risk with IV administration 1
• Clozapine: 8-10 ms mean QTc prolongation 1

High QTc Effect (>10 ms)

• Pimozide: 13 ms mean QTc prolongation 1
• Ziprasidone: 5-22 ms mean QTc prolongation 1
• Thioridazine: 25-30 ms mean QTc prolongation (FDA black box warning) 1

Clinical Implications and Risk Stratification

High-Risk Situations for QTc Prolongation

• Female gender, age >65 years 1
• Underlying long QTc (>500 ms) 1
• Electrolyte abnormalities (especially hypokalemia, hypomagnesemia) 1
• History of prior sudden cardiac death 1
• Concomitant use of other QTc-prolonging medications 1
• Pre-existing cardiovascular disease 1, 4

Monitoring Recommendations

• Baseline ECG before initiating antipsychotic therapy 1
• Follow-up ECG after dose titration 1
• Consider medication adjustment if QTc exceeds 500 ms or increases by >60 ms from baseline 1
• Monitor electrolytes, particularly potassium levels 1

Evidence-Based Selection Algorithm

1. First-line options (for patients with QTc concerns):

   • Aripiprazole - no measurable effect on QTc interval 1, 3
   • Brexpiprazole - no clinically significant QTc prolongation 2, 3, 5

2. Second-line options (if first-line not suitable):

   • Olanzapine - minimal QTc effect (2 ms) 1, 3
   • Lurasidone - minimal QTc effect based on real-world data 4, 5

3. Third-line options (use with caution and monitoring):

   • Risperidone (0-5 ms) 1
   • Quetiapine (6 ms) 1, 6

4. Avoid if possible (in patients with QTc concerns):

   • Ziprasidone (5-22 ms) 1
   • Thioridazine (25-30 ms, FDA black box warning) 1
   • IV haloperidol (higher risk than oral) 1

Common Pitfalls and Caveats

• Route of administration matters: IV haloperidol carries a higher risk of QTc prolongation and arrhythmias than oral or IM administration 1

• Drug interactions: Avoid combining multiple QTc-prolonging medications 1

• Individual variability: Genetic factors affecting drug metabolism can influence QTc response 4, 7

• Sex differences: Women are at higher risk of QTc prolongation and torsades de pointes with antipsychotics 1, 7

• Monitoring beyond ECG: Regular assessment of electrolytes is essential, especially potassium and magnesium 1, 4

• Dose-dependent effects: Higher doses generally increase the risk of QTc prolongation 4, 8

When QTc prolongation is a significant concern, aripiprazole and brexpiprazole represent the safest options with minimal to no effect on cardiac repolarization, followed by olanzapine as a reasonable alternative 1, 2, 3.