QT Prolongation and Monitoring

QT Prolongation is associated with many psychotropic medications (especially antipsychotics) and some are linked to serious ventricular arrhythmias (e.g. - Torsades de Pointes) and sudden cardiac death. The risk of QT prolongation is likely dose-related, but the overall absolute risk is low. ECG monitoring is recommended for all patients on QT-prolonging agents, especially those taking medications long-term. There are few guidelines on the monitoring of QT, but it is generally recommended when a QT-prolonging agent is started, or if there are there is a dose increase. Yearly monitoring is suggested by some guidelines.

Why is QT prolongation bad?

The QT interval indicates the length of cardiac repolarization (the time for the ventricles to contract and relax). Simply put, an increase in the QT interval causes heterogeneity in electrical phasing in different ventricular structures of the heart. This can cause events like ventricular extrasystole and Torsades de Pointes, leading to ventricular fibrillation and sudden death.[1]

The QT interval is an interval between the start of the QRS complex to the end of the T Wave on an electrocardiocgram (in milliseconds).

Since different hear rates can affect the QT interval, the QT interval is usually reported as the QTc (QT corrected for heart rate). There are 4 types of formulae to correct the QT interval, mainly Bazett, Fredericia (also spelled Fridericia), Framingham, and Hodges. Each type of correction formula can give markedly different QTc values. The Bazett correction (which is most commonly used) has been found to overestimate the number of patients with potentially dangerous QTc prolongation, especially with higher heart rates. This overcall can lead to unnecessary withholding of first-line medications. The Fredericia and Framingham corrections have the best rate correction, and are recommended for patients starting new drugs or on shorter regimens.[2]

Regardless of the different corrections, the QTc remains an imprecise indicator of risk of Torsades de Pointes and cardiac mortality. Combining QTc with T-wave morphology better predicts the risk for Torsades de Pointes. Some patients whose QTc falls above the traditional upper limits can also take medications that alter cardiac repolarization without developing Torsades.[3]

QT interval Fig. 1

Management of QT Prolongation

Adapted from: Taylor, D. M., Barnes, T. R., Young, A. H. (2018). The Maudsley prescribing guidelines in psychiatry.
QTc* (men) QTc* (women) Action Cardiology Referral
<440ms <470ms None unless abnormal T‐wave morphology No
440-500ms 470-500ms Consider reducing dose or switching to drug of lower effect and repeat ECG Consider
>500ms >500ms Repeat ECG. Stop suspected QT-prolonging agents(s) and switch to drug less QT effects Yes

Risk factors for QT prolongation include:

  • Female gender
  • Older age (> 65years old)
  • Eating disorders
  • Heart disease (recent myocardial infarction, congestive heart failure, bradyarrhythmias)
  • Electrolyte disturbances (hypokalemia and hypomagnesia)
  • Renal impairment (CrCl <20ml/min)

Other Factors That Affect QTc

  • There is normal physiological variation in the QTc interval. QT can vary with gender, time of day, food intake, alcohol intake, menstrual cycle, ECG lead placement
  • Plasma levels can also change QTc prolongation is most prominent at peak drug plasma levels and least obvious at trough levels.

The list of medications here will focus on psychotropic medications. Non-psychotropic medications that also affect QT include: antibiotics, antimalarials, and antiarrhythmics.

Antipsychotics

Adapted from: Taylor, D. M., Barnes, T. R., Young, A. H. (2018). The Maudsley prescribing guidelines in psychiatry.
No effect Brexpiprazole
Cariprazine
Lurasidone
Low effect Aripiprazole
Asenapine
Clozapine
Flupenthixol
Fluphenazine
Loxapine
Perphenazine
Olanzapine
Paliperidone
Risperidone
Moderate effect Amisulpride
Chlorpromazine
Haloperidol
Quetiapine
Ziprasidone
High effect • Any intravenous antipsychotic
• Pimozide
• Sertindole
• Any drug doses exceeding recommended maximum
Unknown Zuclopenthixol

Antidepressants

Adapted from: Taylor, D. M., Barnes, T. R., Young, A. H. (2018). The Maudsley prescribing guidelines in psychiatry.
None • Agomelatine
Bupropion
Fluoxetine
Fluvoxamine
MAOIs
Mirtazapine
Moclobemide
Vilazodone
• Reboxetine
Paroxetine
Sertraline
Vortioxetine
Low effect Duloxetine
Trazodone
Moderate effect Citalopram
Escitalopram
Venlafaxine
High effect Tricyclics

Opioids

High effect Methadone

Methadone, either alone or combined with other QT‐prolonging agents, can cause QT interval prolongation. Patients on more than 100mg of methadone daily should be closely monitored as the risk of QTc prolongation is dose related.

Cocaine is also a QT‐prolonging agent.

  • If on antidepressant: try switching to: bupropion, SSRIs other than citalopram/escitalopram
  • If on antipsychotic: try switching to: aripiprazole, and lurasidone
  • If on methadone: plan switch to buprenorphine, Suboxone
  • Remove interacting drugs that prolong metabolism and increase plasma levels of QT-prolonging drugs (e.g. - omeprazole can increase plasma levels of escitalopram and citalopram)
  • If the QTc is not normal, i.e. > 500, order Mg and K levels. If these levels are low, then it should be replaced and the ECG repeated again.
  • Correct bradycardia