QT (QTc) 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.
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 heart 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, Framingham, and Hodges. Each type of correction formula can give markedly different QTc values.
The Bazett correction (which is most commonly used and found in most preprogrammed ECG machines that calculate the QTc), however, it tends to:
This overcall can lead to unnecessary withholding of first-line medications. Thus manual measurement using the Fredericia or Framingham corrections, or population-based nomograms have the best rate correction. These alternative methods 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]
Different clinical guidance exists for the cut off scores for QTc intervals (which also depend on correction methods). Below are two guidelines to guide decision making.
QTc* (men) | QTc* (women) | Action | Cardiology Referral |
---|---|---|---|
<440 ms | <470 ms | None unless abnormal T‐wave morphology | No |
440 to 500 ms | 470 to 500 ms | Consider reducing dose or switching to drug of lower effect and repeat ECG | Consider |
>500 ms | >500 ms | Repeat ECG. Stop suspected QT-prolonging agents(s) and switch to drug less QT effects | Yes |
QTc* (men) | QTc* (women) | Interpretation |
---|---|---|
<430 ms | >450 ms | Normal |
431 to 470 ms | 451 to 480 ms | Borderline |
>470 ms | >480 ms | Prolonged |
Risk factors for QT prolongation include:
The list of medications here will focus on psychotropic medications. Non-psychotropic medications that also affect QT include: antibiotics, antimalarials, and antiarrhythmics.
No effect | • Brexpiprazole • Cariprazine • Lurasidone |
---|---|
Low effect | • Aripiprazole*[5] • Asenapine • Clozapine • Flupenthixol • Fluphenazine • Loxapine • Perphenazine • Paliperidone |
Moderate effect | • Amisulpride • Risperidone • Olanzapine • Quetiapine • Haloperidol • Chlorpromazine |
High effect | • Risperidone |
Unknown | • Zuclopenthixol |
None | • Agomelatine • Bupropion • Fluoxetine* • Duloxetine*[6][7] • Fluvoxamine*[8] • MAOIs • Mirtazapine • Moclobemide • Vilazodone • Reboxetine • Paroxetine*[9] • Sertraline*[10] • Vortioxetine |
---|---|
Low effect | • Trazodone |
Moderate effect | • Citalopram • Escitalopram • Venlafaxine |
High effect | • Tricyclics |
High effect | • Methadone |
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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.