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Guide to QT-prolonging medication

Updated: 19 minutes ago

"Cutie" (QT) interval prolongation

On electrocardiogram (ECG), the QT interval reflects the rate of electrical conduction through the ventricles as they contract and relax. The useful number for our purposes is the QTc interval, which is QT corrected for heart rate, which takes into account that QT is naturally longer at slower heart rate.

normal sinus rhythm EKG P Q R S T waves

QT prolongation is a delay in cardiac conduction that can trigger Torsades de pointes (TdP, French “twisting of points”) in the context of other risk factors.


Around 50% of patients with TdP are asymptomatic. The most common symptoms are syncope, palpitations, and dizziness. However, sudden cardiac death is the presenting symptom in up to 10% of cases. 


QTc > 500 milliseconds can be dangerous. 


Depending on the reference source, long QTc is defined as either: 

  • ≥ 450 msec per gepirone prescribing information

  • >470 msec = 99th percentile in males

  • >480 msec = 99th percentile in females


Schwartz scoring toward suspicion of inherited long QT syndrome:

  • ≥ 450 = 1 point

  • ≥ 460 = 2 points

  • 480 msec = 3 points

An increase in QTc > 60 msec caused by a medication would be of concern. 


Many psychotropic medications prolong QT. In overdose scenarios involving antidepressants or antipsychotics, QT interval is often long, necessitating a trip to the ICU. Tricyclic antidepressants (TCAs) are particularly deadly in overdose due to disruption of cardiac conduction manifested by, among other measures, prolonged QT.


When considering QT prolonging medications it is important to assess benefit-risk taking into account other risk factors for TdP—although absolute risk related to medication is extremely low.


Overdose of medication can can lead to TdP.  Mortality from a single-drug overdose of citalopram (a known QT prolonger) is about 1 in 2,500, compared to less than 1 in 10,000 for escitalopram which does not prolong QT (Nelson & Spyker, 2017). 


The 2011 FDA warning of QT prolongation with citalopram > 40 mg resulted in unintended negative consequences in VA patients (Rector et al, 2016). For patients whose citalopram dose was decreased, all-cause death was 2.5 times higher without change in rate of hospitalization for arrhythmias.


Risk factors for Torsades (TdP)


  ► Bradycardia

  ► QTc > 500

  ► Congenital long QT syndrome

  ► Cardiac disease (structural or functional)

  ► Family history of sudden cardiac death

  ► Hypokalemia (low K+)

  ► Hypomagnesemia (low Mg+)

  ► Hypocalcemia (low Ca++)

  ► Eating disorders (electrolyte abnormalities)

  ► Hepatic insufficiency

  ► Renal insufficiency 

  ► Hemodialysis (electrolyte abnormalities)

  ► ICU patients

  ► QT prolonging medication administered intravenously 

  ► Concomitant CYP inHibiting medications that can raise serum levels of QT-prolonging medications

  ► Older age

  ► Women (~two thirds of TdP cases, longer QTc at baseline)


The risk of torsades is the highest within the first few days of initiating treatment with a QT prolonger, or with rapid IV infusion. Do not add a QT-prolonging medication when QTc is near 500 msec. However, a long QT does not always require discontinuation of contributing medication(s). 


For most drugs that prolong QT, the risk of TdP is so low that routine ECG screening is unnecessary for most patients. Even combinations of QT-prolonging medications below the high risk category are unlikely to pose a clinical risk in absence of risk factors. Do not combine two high risk medications.


Congenital Long QT Syndrome (LQTS)


Inherited (as opposed to acquired) LQTS affects about 1 in 7,000 people.  Some genetically proven cases of LQTS are concealed at baseline, with QTc within the normal range. 

Congenital long QT syndrome msec QTc

In the US LQTS results in about 3,500 deaths a year due to TdP. Symptoms may include presyncope, syncope, or palpitations. While arrhythmias can occur at any time, in some forms of LQTS they are seen in response to exercise, mental stress, or a sudden loud noise. Individuals may experience seizure-like activity as a result of reduced blood flow to the brain during an arrhythmia. 


Most patients with LQTS experience diagnosable signs and symptoms in childhood and adolescence, but these cases may be mistaken for benign syncope or seizure (London & Zegre-Hemsey et al, 2020).


Management may include beta blockers, supplemental potassium, or  an implantable cardiac defibrillator.


Risk of Drug-Induced QT Prolongation


The FDA is unlikely to approve new drugs prolong mean QT interval by >20 msec. For most medications, extent of QT prolongation is dose dependent.


QT / QTc prolongation antipsychotics list : pimozide, thioridazine, haloperidol, quetiapine (Seroquel), ziprasidone (Geodon) magnitude of effect

QT Prolongation by Antipsychotics

List of QT / QTc prolongation by antipsychotics with msec quetiapine Seroquel

Antidepressants

QT / QTc prolongation antidepressants: Gepirone (Exxua), TCAs, tricyclics, citalopram Celexa, escitalopram (Lexapro)

Mechanism of Drug-Induced QT Prolongation


QT prolongation is caused when a medication blocks hERG potassium ion channels in the heart, leading to inhibition of the cardiac delayed rectifier potassium current.


About 40% of cases of congenital long QT syndrome (LQTS) are caused by hERG mutations (Went et al, 2021).

Mechanism of QT prlongation hERG potassium channels by Jason Cafer MD Cafermed
Mechanism of drug / medication induced QT / QTc prolongation  hERG
Intracellular and extracellular concentration of potassium, magnesium, sodium, and calcium

Mascots / Mnemonics for QT-prolonging drugs


Mnemonics for QT prolonging FGA antipsychotics Thioridazine (Mellaril), Pimozide (Orap), haloperidol (Haldol) and droperidol
QT / QTc prolonging SGA antipsychotics - Quetiapine (Seroquel) and ziprasidone (Geodon)
QTc / QT prolongation by antidepressants gepirone (Exxua), tricyclics (TCAs), and citalopram (Celexa) cafermed
QT / QTc prolongation by flecainide, amiodarone, and dofetilide by Jason Cafer MD Cafermed mnemonics
Class 1A antiarrhythmics
Class 1c Antiarrhythmics
Class 3 antiarrhythmics mnemonics amiodarone dofetilide sotalol
Does fluconazole prolong QT?  Does clarithromycin prolong QT? mnemonics
QT / QTc prolongation mascot mnemonics for ondansetron (ZOFRAN) and granisetron (KYTREL)
QT / QTc prolongation by methadone and propofol mascots mnemonics by Jason Cafer MD
QT / QTc prolongation by pitolisant WAKIX mnemonics



Copyright 2024 CaferMed Publishing. Intended for prescribers.

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