What electrocardiogram (ECG) changes are expected in a nortriptyline (tricyclic antidepressant) overdose?

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From the Guidelines

Nortriptyline overdose is expected to cause characteristic ECG changes, including QRS prolongation, rightward deviation of the terminal 40 ms QRS axis, and sinus tachycardia, as a result of its sodium channel blocking effects. These changes can be observed in the electrocardiogram and are crucial in managing the overdose. The most common ECG findings include:

  • Prolongation of the QRS complex (greater than 100 ms)
  • Rightward deviation of the terminal 40 ms QRS axis
  • Prolongation of the QT/QTc interval
  • Sinus tachycardia
  • A prominent R wave in lead aVR (R wave > 3 mm)
  • ST segment and T wave changes
  • Various arrhythmias including ventricular tachycardia, ventricular fibrillation, or heart blocks, as described in the 2023 American Heart Association focused update 1.

The QRS duration correlates with the severity of toxicity, with intervals exceeding 160 ms associated with increased risk of seizures and ventricular arrhythmias, as noted in the context of sodium channel blocker poisoning 1. Monitoring these ECG parameters is crucial in managing nortriptyline overdose, as they help guide treatment decisions, including sodium bicarbonate administration, which is indicated when QRS prolongation occurs, as supported by the therapeutic intervention with the most evidence 1.

From the FDA Drug Label

Changes in the electrocardiogram, particularly in QRS axis or width, are clinically significant indicators of tricyclic antidepressant toxicity A maximal limb-lead QRS duration of ≥ 0. 10 seconds may be the best indication of the severity of the overdose.

The expected ECG changes in a nortriptyline overdose include:

  • Changes in the QRS axis or width
  • A maximal limb-lead QRS duration of ≥ 0.10 seconds, which may indicate the severity of the overdose. 2

From the Research

ECG Changes in Nortriptyline Overdose

The expected ECG changes in a nortriptyline (tricyclic antidepressant) overdose include:

  • Prolongation of the PR, QRS, and QT intervals 3
  • Nonspecific ST segment and T wave changes 3
  • Atrioventricular block 3
  • Right axis deviation of the terminal 40 ms vector of the QRS complex in the frontal plane (T 40 ms axis) 3
  • Brugada pattern (downsloping ST segment elevation in leads V1-V3 in association with right bundle branch block) 3
  • Wide QRS complex, with a QRS duration > 100 ms being a predictor of serious complications 3, 4
  • Sinus tachycardia, due to anticholinergic activity and inhibition of norepinephrine uptake by tricyclic antidepressants 3
  • Bradyarrhythmias (due to atrioventricular block) and tachyarrhythmias (supraventricular and ventricular) may occur 3
  • Torsade de pointes, although uncommon 3

Predictive Value of ECG Parameters

The predictive value of ECG parameters for serious complications in tricyclic antidepressant overdose is:

  • QRS duration > 100 ms, which appears to be a better predictor of serious complications than an elevated serum tricyclic antidepressant level 4
  • QRS duration > 120 ms, which has a stronger association with the occurrence of arrhythmia 5
  • QTc > 500, which has a stronger association with the occurrence of arrhythmia 5
  • R/S ratio in aVR > 0.7, which is most strongly related to arrhythmia, but has estimated positive and negative predictive values of only 41% and 95%, respectively 5
  • Terminal 40-ms frontal plane QRS vector (T40), which reaches statistical significance regarding prediction of serious events 6

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Tricyclic antidepressant poisoning.

Cleveland Clinic journal of medicine, 2000

Research

Risk assessment of severe tricyclic antidepressant overdose.

Human & experimental toxicology, 2009

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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