What psychotropic medication causes QT (QT interval) prolongation, leading to a widened QRS (QRS complex)?

From the Guidelines

Tricyclic antidepressants (TCAs) are the primary psychotropic medications that cause QRS prolongation on electrocardiograms. Specific examples include amitriptyline, imipramine, desipramine, nortriptyline, and clomipramine 1. This effect occurs because TCAs block sodium channels in cardiac tissue, which slows cardiac conduction and widens the QRS complex. QRS prolongation becomes clinically significant when it exceeds 100 milliseconds, with serious toxicity concerns when it surpasses 120 milliseconds. In overdose situations, QRS widening greater than 160 milliseconds is associated with increased risk of seizures and ventricular arrhythmias.

Key Points to Consider

• Other psychotropic medications that can affect QRS include certain antipsychotics like thioridazine and ziprasidone, though to a lesser extent than TCAs 1.
• Patients with pre-existing cardiac conduction abnormalities, electrolyte disturbances, or those taking other QRS-prolonging medications are at higher risk for these effects.
• Sodium bicarbonate administration is the standard treatment for TCA-induced QRS prolongation in overdose situations.
• The risk of QRS prolongation and associated arrhythmias should be carefully evaluated in patients taking psychotropic medications, particularly those with underlying cardiac conditions or taking multiple medications that can affect cardiac conduction 1.

Clinical Implications

• Clinicians should be aware of the potential for QRS prolongation and associated arrhythmias in patients taking psychotropic medications, particularly TCAs and certain antipsychotics.
• Patients should be monitored closely for signs of QRS prolongation and arrhythmias, particularly in overdose situations or when taking multiple medications that can affect cardiac conduction.
• Sodium bicarbonate administration should be considered in patients with TCA-induced QRS prolongation, and other treatments such as pacing or defibrillation may be necessary in severe cases.

From the FDA Drug Label

QT-Prolongation and Torsade de Pointes Citalopram causes dose-dependent QTc prolongation, an ECG abnormality that has been associated with Torsade de Pointes (TdP), ventricular tachycardia, and sudden death, all of which have been observed in postmarketing reports for citalopram 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. In post marketing experience, there were cases reported of QT prolongation in patients who overdosed on quetiapine

The psychotropic medications that may cause QRS prolongation (more specifically QTc prolongation) are:

• Citalopram: causes dose-dependent QTc prolongation, which can lead to Torsade de Pointes, ventricular tachycardia, and sudden death 2
• Quetiapine: although not associated with a persistent increase in QT intervals in clinical trials, there were cases reported of QT prolongation in post-marketing experience, particularly in overdose situations or with concomitant use of other drugs that prolong the QTc interval 3

From the Research

Psychotropic Medications and QRS Prolongation

• The relationship between psychotropic medications and QRS prolongation is not directly addressed in the provided studies, but it is related to QT prolongation, which can be a precursor to QRS prolongation.
• According to 4, psychotropics are among the most common causes of drug-induced acquired long QT syndrome, which can lead to QRS prolongation.
• Antipsychotics such as haloperidol, thioridazine, sertindole, pimozide, risperidone, ziprasidone, quetiapine, and olanzapine, as well as antidepressants like amitriptyline, imipramine, doxepin, trazadone, and fluoxetine, can depress the delayed rectifier potassium current (IKr) in a dose-dependent manner, potentially leading to QT and QRS prolongation.

Specific Medications and QRS Prolongation

• Haloperidol and thioridazine have been associated with a higher risk of QTc prolongation and potentially QRS prolongation 4.
• Risperidone, olanzapine, and quetiapine have also been linked to QTc prolongation, but the risk of QRS prolongation is not explicitly stated in the provided studies 4, 5, 6.
• Selective serotonin reuptake inhibitors (SSRIs) like escitalopram have been associated with QTc prolongation, but the risk of QRS prolongation is not well established 4, 7, 8.

Risk Factors and QRS Prolongation

• Female gender, concomitant cardiovascular disease, substance abuse, drug interactions, bradycardia, electrolyte disorders, anorexia nervosa, and congenital Long QT syndrome are risk factors for drug-induced LQT syndrome and potentially QRS prolongation 4.