What antipsychotics can cause arrhythmia or prolonged QT(c) interval?

Antipsychotics and QTc Prolongation/Arrhythmia Risk

All antipsychotics can cause QTc prolongation and arrhythmias, but the risk varies dramatically by agent—aripiprazole and brexpiprazole cause essentially no QTc prolongation (0 ms), while thioridazine causes 25-30 ms prolongation with an FDA black box warning and should be avoided. 1

Highest Risk Antipsychotics (Avoid When Possible)

These agents carry the greatest risk of torsades de pointes and sudden cardiac death:

• Thioridazine: 25-30 ms mean QTc prolongation with FDA black box warning for arrhythmias 2, 1
• Pimozide: 13 ms mean QTc prolongation 1
• Ziprasidone: 5-22 ms mean QTc prolongation 2, 1
• Intravenous haloperidol: 7 ms mean QTc prolongation, but IV route carries substantially higher risk than oral/IM administration 2, 1

Both typical and atypical antipsychotics show dose-dependent increases in sudden cardiac death risk, with adjusted incidence-rate ratios ranging from 1.31 to 2.42 for typical agents and 1.59 to 2.86 for atypical agents 2

Moderate Risk Antipsychotics

• Clozapine: 8-10 ms mean QTc prolongation 1
• Quetiapine: 6 ms mean QTc prolongation; FDA label warns of QTc prolongation in overdose and with concomitant QTc-prolonging drugs 1, 3
• Chlorpromazine: Associated with increased risk (RR for 100 mg = 1.37,95% CI 1.14-1.64) 4
• Oral/IM haloperidol: 7 ms mean QTc prolongation, lower risk than IV route 1

Lower Risk Antipsychotics

• Risperidone: 0-5 ms mean QTc prolongation 1
• Olanzapine: 2 ms mean QTc prolongation, minimal effect 1

Safest Options (Preferred When QTc is a Concern)

When QTc prolongation is a concern, choose these agents first:

• Aripiprazole: 0 ms mean QTc prolongation, no measurable effect on QTc interval 1
• Brexpiprazole: No clinically significant QTc prolongation 1

High-Risk Clinical Situations Requiring Extra Caution

Avoid antipsychotics with significant QTc effects in these scenarios:

• Female gender and age >65 years 2
• Baseline QTc >500 ms 2
• Hypokalemia or hypomagnesemia 2
• Concomitant use of other QTc-prolonging medications (see drug interactions below) 2
• History of sudden cardiac death in patient or family 2
• Pre-existing cardiovascular disease, congestive heart failure, or left ventricular hypertrophy 2
• Bradycardia or recent conversion from atrial fibrillation 2
• Congenital long QT syndrome 2

Critical Monitoring Algorithm

Follow this sequence for all patients receiving antipsychotics:

1. Baseline assessment: Obtain ECG before initiating therapy, check potassium and magnesium levels 2
2. Post-initiation: Repeat ECG after dose titration or 7 days after starting therapy 1
3. Ongoing monitoring: Monitor electrolytes throughout treatment, particularly potassium 2, 1
4. Action thresholds:
   • If QTc exceeds 500 ms OR increases by >60 ms from baseline, consider switching to aripiprazole 2, 1
   • Discontinue immediately if torsades de pointes suspected 1

Common Pitfalls and How to Avoid Them

Route of administration matters critically: IV haloperidol carries substantially higher risk than oral or IM routes—always prefer oral/IM administration when possible 2, 1

Drug interactions amplify risk: Avoid combining multiple QTc-prolonging medications. The FDA specifically warns against using quetiapine with Class IA antiarrhythmics (quinidine, procainamide), Class III antiarrhythmics (amiodarone, sotalol), other antipsychotics (ziprasidone, chlorpromazine, thioridazine), or certain antibiotics (gatifloxacin, moxifloxacin) 3

Sex differences are real: Women have higher baseline risk of QTc prolongation and torsades de pointes with all antipsychotics 2

Don't rely on TSH alone: If monitoring thyroid function with quetiapine, measure both TSH and free T4, as quetiapine may affect the hypothalamic-pituitary axis 3

Electrolyte correction is mandatory: Always correct hypokalemia (to >4.5 mEq/L) and hypomagnesemia before initiating antipsychotics and maintain normal levels throughout treatment 2, 1

Management of Torsades de Pointes

If torsades de pointes occurs:

1. Immediately discontinue the offending antipsychotic 1
2. Administer IV magnesium sulfate to suppress episodes 1
3. Correct potassium to >4.5 mEq/L 1
4. Consider temporary cardiac pacing for recurrent episodes 1
5. Use isoproterenol only if pacing unavailable 1