Tricyclic Antidepressant Overdose on ECG

What it looks like on ECG

In the initial stage of intoxication, sinus tachycardia (anticholinergic effect of TCAs) with a normal or slightly widened QRS is typical. As the drug concentration increases, QRS complex widening due to fast sodium channel blockade predominates — ventricular depolarization slows down, which is visible in all leads, but the maximum width is measured in the lead where it is greatest.

A classic additional sign is changes in lead aVR: a terminal R wave with an amplitude >3 mm and an R/S ratio >0.7. Given the appropriate history (ingestion or suspected ingestion of TCAs), this sign supports the diagnosis, but it is not specific to TCAs — this pattern has been described in poisoning by any sodium channel blockers. The mechanism is classically explained as follows: the terminal part of ventricular depolarization (late vector directed rightward and upward) slows down due to sodium channel blockade, and this vector's direction is close to the axis of lead aVR; in some patients, the pattern may differ due to the baseline QRS morphology.

As progression occurs, AV blocks, bradycardia, and ventricular tachycardia (often monomorphic, resembling right bundle branch block in morphology) and ventricular fibrillation are possible. The axis shifts, forming a characteristic 'right superior' terminal vector.

Mechanism

TCAs block fast sodium channels of cardiomyocytes (an effect similar to class IA/IC antiarrhythmics), slowing phase 0 of the action potential and conduction through the His-Purkinje system and ventricular myocardium. This manifests as QRS widening. The terminal part of depolarization suffers the most, which is classically associated with a vector directed rightward and upward — hence the terminal R wave in aVR in some patients. Additionally, TCAs block potassium channels, slowing repolarization (true JT prolongation is possible, not just secondary QT prolongation due to a wide QRS), and have anticholinergic and alpha-blocking effects (tachycardia, hypotension). Severe sodium channel blockade reduces contractility and creates a risk of re-entry ventricular arrhythmias.

Causes

• Intentional or accidental overdose of amitriptyline, imipramine, clomipramine, doxepin, and other TCAs
• Toxicity against the background of reduced hepatic metabolism (hepatic impairment) and drug interactions, including CYP2D6 inhibition; renal impairment may be a contributing factor, but not the primary cause of toxicity from therapeutic doses
• Co-ingestion with other sodium channel blockers (quinidine, flecainide, carbamazepine) increases cardiotoxicity
• Pediatric age — high sensitivity even to small doses

Differential diagnosis

• Poisoning by other sodium channel blockers (carbamazepine, quinidine, flecainide, cocaine) — a similar picture, can only be distinguished by history and clinical dynamics
• Hyperkalemia — also widens QRS, but a tall peaked T wave and shortening/disappearance of the P wave are characteristic; an isolated R wave in aVR is not a reliable differentiating sign, as it can also appear in other causes of delayed terminal right ventricular forces
• Right bundle branch block — QRS widening and slurring in V1; signs in aVR (terminal R, R/S ratio) are non-specific and do not independently rule out RBBB or differentiate it from toxic sodium channel blockade — one should rely on QRS dynamics, the baseline ECG prior to intoxication, the diffuse nature of intraventricular conduction delay, and the clinical context
• Brugada syndrome — type 1 ST-segment elevation in right precordial leads V1–V2, preferably recorded with electrodes placed in the 2nd–4th intercostal spaces; QRS duration and the presence or absence of an R wave in aVR are not exclusion criteria, and some TCAs and other sodium-channel-blocking drugs can induce a Brugada-like phenocopy pattern — differentiation requires clinical evaluation and history
• Ventricular tachycardia of other etiology — in TCA-induced VT, the key clue remains preceding QRS widening and a history of drug ingestion

Clinical significance and management

QRS widening ≥100 ms warrants vigilance for seizures, while ≥160 ms is a predictor of ventricular tachycardia and ventricular fibrillation. A terminal R in aVR >3 mm supports the presence of significant sodium channel blockade and, considering the history, helps suspect TCAs, but it does not replace clinical evaluation or distinguish TCAs from other sodium-channel-blocking poisons.

Guideline-level management: continuous cardiac monitoring and serial ECG recordings, assessing QRS duration dynamics. Indications are categorized by the leading syndrome. For seizures — immediate airway management (ABC) and a benzodiazepine as the first-line agent; antiseizure therapy must not be delayed while waiting for other measures. For QRS widening ≥100 ms, hypotension, or ventricular arrhythmias in the setting of TCA toxicity, the main specific intervention is sodium bicarbonate (bolus, with subsequent infusion if necessary) per local toxicology protocol: raising blood pH and extracellular sodium reduces TCA binding to sodium channels and narrows the QRS. Sodium bicarbonate may also be considered as an adjunctive measure in seizures with signs of sodium channel blockade, but it does not replace benzodiazepines and airway management. When administering bicarbonate, monitoring pH, sodium, and potassium is mandatory to prevent excessive alkalosis and hypernatremia. Additionally — maintaining normal circulating blood volume and blood pressure; for ventricular arrhythmias, avoid class IA and IC antiarrhythmics (they increase sodium channel blockade). Diagnosis and emergency decisions are based primarily on clinical presentation, ECG, and condition dynamics; toxicological screening plays an auxiliary role, is often limited in sensitivity, and blood TCA concentrations correlate poorly with the severity of acute cardiotoxicity, so waiting for lab results must not delay sodium bicarbonate and resuscitation efforts. The decision regarding specific dosages and infusion regimens is made by the toxicology/resuscitation team.

Common interpretation errors

• Assessing only the QRS duration in a single lead rather than finding the maximum value across all leads
• Failing to measure the R wave and the R/S ratio in aVR and assuming they are diagnostically specific to TCAs, when they are merely supportive signs of sodium channel blockade
• Using the absence or presence of a terminal R in aVR as an independent criterion to rule out right bundle branch block or Brugada syndrome
• Interpreting wide-complex tachycardia as primary ventricular tachycardia without considering intoxication
• Categorically treating QT prolongation in TCA poisoning as solely secondary (due to a wide QRS), without considering the possibility of true repolarization delay and the risk of torsades de pointes
• Ignore ECG dynamics — as toxicity increases, the picture changes rapidly; a single "normal" ECG does not rule out the risk

Frequently asked questions

Related terms

More in "Pharmacology and Toxicology"

Entire section

Sources

• Goldberger's Clinical Electrocardiography, latest edition
• Surawicz, Knilans. Chou's Electrocardiography in Clinical Practice
• Hampton. The ECG in Practice

Educational material for medical students and physicians. Does not replace clinical guidelines and physical examination; the ECG must always be interpreted in conjunction with the clinical picture.