From the Guidelines
Amitriptyline overdose primarily causes toxicity through the blockade of cardiac sodium channels, leading to hypotension, dysrhythmia, and death, as well as by mimicking a Brugada type 1 ECG pattern, as supported by the 2020 American Heart Association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care 1. The mechanisms of amitriptyline overdose are multifaceted, involving:
- Blockade of sodium channels in the heart, disrupting cardiac conduction and potentially causing life-threatening arrhythmias, as evidenced by characteristic ECG findings including tachycardia and QRS prolongation with a right bundle branch pattern 1.
- Anticholinergic properties resulting in the classic "anticholinergic toxidrome" with symptoms like dry mouth, blurred vision, urinary retention, and hyperthermia.
- Blockade of alpha-adrenergic receptors, causing vasodilation and hypotension.
- Blockade of histamine receptors, contributing to sedation.
- Excessive levels of norepinephrine and serotonin due to the blockade of their reuptake, affecting various body systems. Key cardiovascular effects include:
- Tachycardia
- Hypotension
- QRS prolongation on ECG Treatment approaches, as outlined in the guidelines, include:
- Sodium boluses and serum alkalization, typically achieved through administration of sodium bicarbonate boluses, to counteract cardiac toxicity 1.
- Administration of magnesium in addition to sodium bicarbonate for patients with TCA-induced hypotension, acidosis, and/or QRS prolongation, although the evidence for this is preliminary 1.
From the FDA Drug Label
Deaths may occur from overdosage with this class of drugs. Multiple drug ingestion (including alcohol) is common in deliberate tricyclic antidepressant overdose. Manifestations Critical manifestations of overdose include: cardiac dysrhythmias, severe hypotension, convulsions, and CNS depression, including coma Changes in the electrocardiogram particularly in QRS axis or width, are clinically significant indicators of tricyclic antidepressant toxicity. In addition, a rightward axis shift in the terminal QRS complex together with a prolonged QT interval and sinus tachycardia are specific and sensitive indicators of first generation tricyclic overdose.
The mechanisms of amitriptyline overdose include:
- Cardiac toxicity: leading to cardiac dysrhythmias, severe hypotension, and changes in the electrocardiogram, such as a prolonged QRS duration and QT interval.
- CNS depression: resulting in coma, convulsions, and impaired mental status.
- Other systemic effects: including impaired myocardial contractility, disorders of ocular motility, agitation, hyperactive reflexes, and polyradiculoneuropathy 2.
From the Research
Mechanisms of Amitriptyline Overdose
The mechanisms of amitriptyline overdose involve several key factors, including:
- Anticholinergic effects, which predominate in cases of low-dose ingestion 3
- Cardiotoxicity, seizures, and hypotension, which occur in cases of high-dose ingestion 3
- Blockage of alpha-adrenergic receptors and anticholinergic effects, leading to cardiotoxicity, arrhythmias, and hypotension 4
- Direct local anesthetic actions, blocking sodium channels in cardiac membranes, resulting in ventricular conduction abnormalities and severe ventricular arrhythmias 5
Cardiovascular Toxicity
Cardiovascular toxicity is a major concern in amitriptyline overdose, with effects including:
- ECG abnormalities, arrhythmias, and hypotension 6
- Prolongation of the PR, QRS, and QT intervals, nonspecific ST segment and T wave changes, atrioventricular block, and right axis deviation of the terminal 40 ms vector of the QRS complex in the frontal plane (T 40 ms axis) 6
- Sinus tachycardia, bradyarrhythmias, and tachyarrhythmias, including torsade de pointes 6
- Hypotension resulting from reduced myocardial contractility and reduced systemic vascular resistance due to alpha-adrenergic blockade 6
Treatment Options
Treatment options for amitriptyline overdose include:
- Sodium bicarbonate to rapidly convert ventricular tachycardia to normal sinus rhythm 5
- Intravenous lipid emulsion (ILE) as rescue therapy in cases of cardiac arrest 4
- Esmolol for intractable ventricular arrhythmias in major amitriptyline toxicity 7
- Supportive treatments, including mechanical ventilatory support and correction of electrolytes 3, 7