What are Class B and B* drugs that can prolong the QT interval?

Classification of QT-Prolonging Psychotropic Medications

Class B drugs are psychotropic medications with a propensity for inducing QT prolongation, while Class B drugs are those with pronounced QT prolongation, documented cases of Torsades de Pointes (TdP), or other serious arrhythmias.* 1

Drug Classification System

The European Heart Journal guidelines establish a three-tier classification system for psychotropic medications based on arrhythmia risk 1:

• Class A: Drugs without any risk of QT prolongation or TdP 1
• Class B: Drugs with a propensity for inducing QT prolongation 1
• Class B*: Drugs with pronounced QT prolongation, documented TdP cases, or other serious arrhythmias 1

This classification merges the categories of 'drugs to be avoided by congenital long QT', 'drugs with conditional TdP risk', and 'drugs with known TdP risk' into the single Class B* designation 1.

Specific Class B and B* Medications

Antipsychotics

Highest Risk (Class B):*

• Thioridazine remains the antipsychotic most strongly associated with QT prolongation and TdP risk 2, 3
• Intravenous haloperidol in high doses carries clinically significant risk, though this may be confounded by its use in medically ill populations 2, 4
• Pimozide has the highest potential for QT prolongation among typical antipsychotics 3

Moderate Risk (Class B):

• Ziprasidone appears most likely among atypical antipsychotics to prolong the QTc interval, causing approximately 6 ms of prolongation on average 5, 2, 4, 6
• Iloperidone is possibly associated with significant QT prolongation 4
• Quetiapine has moderate QT-prolonging effects with approximately 6 ms of prolongation 5, 6
• Amisulpride has been reported in a few TdP cases 6

Lower Risk:

• Aripiprazole appears safest from a QT standpoint among atypical antipsychotics 4

Both typical and atypical antipsychotics show dose-dependent increases in sudden cardiac death risk, with adjusted incidence-rate ratios from 1.31 to 2.42 for typical agents and 1.59 to 2.86 for atypical agents 1.

Antidepressants

Tricyclic Antidepressants (Class B/B):*

• All TCAs prolong the QT interval and are associated with increased cardiac arrest risk (OR = 1.69) 1, 7
• Amitriptyline and maprotiline have specific reports of TdP 1
• TCAs have higher rates of QT prolongation than SSRIs, particularly at higher concentrations and in overdose 3

SSRIs (Class B):

• Citalopram causes the most QT prolongation among SSRIs, leading to FDA and EMA dose restrictions (maximum reduced for patients >60 years) 1, 7, 2, 4
• Escitalopram prolongs QT to a lesser extent than citalopram but still requires dose restrictions 1, 4
• Fluoxetine, paroxetine, and sertraline have been reported in a few TdP cases 6

SNRIs (Class B):

• Venlafaxine has been associated with TdP in a few cases 6
• SNRIs as a class showed no association with cardiac arrest in registry studies 1, 7

Other Psychotropics

Mood Stabilizers:

• Lithium has divergent reports regarding QT prolongation, but bradycardia, T wave changes, and AV-block have been described 1
• Carbamazepine, lamotrigine, and valproate are generally not associated with severe arrhythmia 1, 5

Anxiolytics:

• Benzodiazepines (including lorazepam) do not affect QT interval and can be safely used 8, 7

Critical Risk Factors for Class B/B* Drugs

When Class B or B* drugs are prescribed, the following risk factors dramatically increase arrhythmia risk 1, 6:

• Age >60-65 years 1, 7, 6
• Pre-existing cardiovascular disease or structural heart disease 1, 6
• Female sex 6
• Bradycardia 1, 6
• Electrolyte disturbances (hypokalemia, hypomagnesemia) 8, 7, 6
• Concomitant use of other QT-prolonging medications 1, 7, 6
• Supratherapeutic or toxic serum concentrations 6
• Hepatic insufficiency 3

Management Algorithm for Class B/B* Drugs

Before initiating Class B/B medications* 1:

1. Obtain medical history focusing on chest pain, dyspnoea, palpitations, syncope, and family history of sudden cardiac death 1
2. Review all medications for drug interactions and other QT-prolonging agents 1
3. Obtain baseline ECG to assess for heart disease, conduction disorders, or prolonged QT 1

If Class A drug is chosen: Commence treatment without further cardiac assessment 1

If Class B/B drug is chosen* 1:

1. Assess and optimize all cardiac risk factors 1
2. Consider alternative drug with more favorable risk profile if possible 1
3. If structural heart disease, QT prolongation, electrolyte disturbances, or cardiac symptoms present, refer to cardiology 1

Follow-up monitoring 1:

• Re-evaluate ECG and symptoms within 1-2 weeks after initiation (at steady-state, >5 drug half-lives) 1
• Repeat ECG after significant dose increases 1
• Discontinue drug if QTc >500 ms or increment >60 ms from baseline 1

Common Pitfalls

Additive effects: Multiple QT-prolonging medications have additive effects that are frequently underrecognized 5, 8

Polytherapy risk: Combining antipsychotics with antidepressants causes significantly greater QT prolongation (24 ± 21 ms) compared to monotherapy (-1 ± 30 ms), with 38% versus 7% exceeding the 450 ms threshold 9

Drug interactions: CYP-system inhibitors (e.g., verapamil) and diuretic-induced hypokalemia substantially increase risk 1

Population assumptions: Assuming all psychiatric medications carry equal QT prolongation risk is incorrect—the variation between agents is substantial 5