Do all psychiatric medications prolong the QTc (corrected QT) interval?

From the Guidelines

No, not all psychiatric medications prolong the QTc interval, and the risk varies among different classes of medications. While some psychiatric medications can affect cardiac conduction and prolong QTc, many do not have this effect or have minimal impact. Medications with higher risk of QTc prolongation include certain antipsychotics (particularly thioridazine, ziprasidone, and high-dose quetiapine), tricyclic antidepressants (especially amitriptyline and imipramine), and the antidepressant citalopram at doses above 40mg daily, as reported in a study published in the European Heart Journal 1.

Medications with Higher Risk of QTc Prolongation

• Certain antipsychotics: thioridazine, ziprasidone, and high-dose quetiapine
• Tricyclic antidepressants: amitriptyline and imipramine
• The antidepressant citalopram at doses above 40mg daily

Medications with Lower Risk

• Most SSRIs: fluoxetine, sertraline, escitalopram
• Many newer antipsychotics: aripiprazole, lurasidone, brexpiprazole
• Mood stabilizers: lithium, lamotrigine, and valproate

When prescribing psychiatric medications, it's essential to consider a patient's baseline QTc interval, other medications they're taking that might also affect QTc, and cardiac risk factors, as emphasized in guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death 1. For high-risk patients or those taking multiple QTc-prolonging medications, ECG monitoring may be necessary, and the use of antipsychotics should be cautious in patients at significant risk for torsades de pointes, as suggested by clinical practice guidelines for the management of pain, agitation, and delirium in adult patients in the intensive care unit 1. The mechanism of QTc prolongation involves blockade of potassium channels in cardiac cells, which delays ventricular repolarization and can potentially lead to dangerous arrhythmias like Torsades de Pointes in susceptible individuals.

Key Considerations

• Patient's baseline QTc interval
• Other medications that might affect QTc
• Cardiac risk factors
• ECG monitoring for high-risk patients
• Caution with antipsychotics in patients at risk for torsades de pointes

From the FDA Drug Label

In clinical trials, quetiapine was not associated with a persistent increase in QT intervals. However, the QT effect was not systematically evaluated in a thorough QT study. The use of quetiapine should be avoided in combination with other drugs that are known to prolong QTc including Class 1A antiarrythmics (e.g., quinidine, procainamide) or Class III antiarrythmics (e.g., amiodarone, sotalol), antipsychotic medications (e.g., ziprasidone, chlorpromazine, thioridazine), antibiotics (e.g., gatifloxacin, moxifloxacin), or any other class of medications known to prolong the QTc interval (e.g., pentamidine, levomethadyl acetate, methadone)

Not all psych meds prolong QTc. The provided drug label for quetiapine indicates that it was not associated with a persistent increase in QT intervals in clinical trials, although the QT effect was not thoroughly evaluated. However, it does mention that other antipsychotic medications, such as ziprasidone, chlorpromazine, and thioridazine, are known to prolong the QTc interval 2.

From the Research

QTc Prolongation and Psychotropic Medications

• Not all psychotropic medications prolong the QTc interval, as evidenced by studies that have investigated the effects of various medications on QTc interval length 3, 4, 5, 6, 7.
• The risk of QTc prolongation is associated with certain medications, such as antipsychotics and antidepressants, particularly when used in combination or in patients with underlying cardiovascular conditions 4, 5, 7.
• Advanced age and cardiovascular comorbidity are also associated with an increased risk of QTc prolongation, regardless of medication use 3.

Medication-Specific Effects on QTc Interval

• Antipsychotic monotherapy may not significantly prolong the QTc interval, whereas combination therapy with antidepressants or other medications may increase the risk of QTc prolongation 4.
• Certain antipsychotics, such as haloperidol and olanzapine, have been associated with QTc prolongation, although the risk may be lower with other medications, such as risperidone and clozapine 4, 5.
• The risk of QTc prolongation with antidepressants is generally lower than with antipsychotics, although certain medications, such as citalopram and escitalopram, may still pose a risk 4, 7.

Monitoring and Management of QTc Prolongation

• Routine ECG monitoring is not necessarily recommended for all patients taking psychotropic medications, although it may be useful in patients with underlying cardiovascular conditions or those taking medications with a high risk of QTc prolongation 5, 6.
• A thorough assessment of medication interactions and side effects, as well as careful monitoring of patients with co-occurring medical or mental health conditions, can help minimize the risk of QTc prolongation 7.