What are the side effects and treatment for a high dose ingestion of amitriptyline (tricyclic antidepressant)?

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Management of Amitriptyline Overdose

Sodium bicarbonate administration is the cornerstone of treatment for amitriptyline overdose, particularly for cardiac conduction abnormalities and QRS prolongation.

Clinical Manifestations of Amitriptyline Overdose

Amitriptyline overdose presents with a range of potentially life-threatening symptoms that typically develop within 30 minutes and peak between 2-6 hours after ingestion 1:

Cardiovascular Effects

  • Sinus tachycardia (most common, occurring in ~66% of cases) 1
  • QRS prolongation (>120 ms indicates severe toxicity) 2
  • QT prolongation and rightward axis shift in terminal QRS complex 2
  • Ventricular arrhythmias (including torsades de pointes)
  • Hypotension (occurs in ~7% of cases) 1

Neurological Effects

  • Altered mental status (occurs in ~78% of cases) 1
  • Seizures
  • Coma
  • Respiratory depression requiring mechanical ventilation (in ~9% of cases) 1

Anticholinergic Effects

  • Dilated pupils
  • Hyperthermia
  • Dry mouth
  • Urinary retention
  • Visual hallucinations
  • Agitation

Emergency Management Algorithm

1. Initial Stabilization

  • Secure airway, breathing, and circulation
  • Obtain ECG immediately and initiate cardiac monitoring 2
  • Establish IV access
  • Monitor vital signs continuously

2. Gastrointestinal Decontamination

  • Perform gastric lavage if presentation is within 1 hour of ingestion 2
  • Administer activated charcoal (repeated doses may be beneficial) 3
  • IMPORTANT: Emesis is contraindicated due to risk of rapid deterioration 2

3. Cardiovascular Management

  • For QRS prolongation ≥0.10 seconds (primary intervention):

    • Administer sodium bicarbonate 1-2 mEq/kg IV bolus 4
    • Target serum pH 7.45-7.55 2
    • Continue sodium bicarbonate infusion as needed to maintain alkalosis
    • Monitor pH frequently to avoid excessive alkalosis (pH >7.60) 2
  • For refractory arrhythmias:

    • Consider lidocaine if unresponsive to sodium bicarbonate 2
    • AVOID Class IA and IC antiarrhythmics (quinidine, disopyramide, procainamide) as they may worsen toxicity 2
  • For hypotension:

    • Administer IV fluid boluses
    • If refractory, use vasopressors (epinephrine and norepinephrine are more effective than dopamine) 4

4. Neurological Management

  • For seizures: Administer benzodiazepines (first-line)
  • For severe agitation: Consider benzodiazepines
  • For anticholinergic symptoms: Consider physostigmine in selected cases with pronounced symptoms 3

5. Advanced Interventions for Refractory Cases

  • Consider ECMO for cardiac arrest or refractory shock due to severe toxicity 4
  • Hemodialysis and hemoperfusion may be considered in severe cases, though evidence is limited 3

Monitoring and Disposition

  • Minimum 6 hours of cardiac monitoring for all patients with suspected overdose 2

  • Extended monitoring (24+ hours) for patients with:

    • Any signs of toxicity
    • QRS prolongation
    • Altered mental status
    • Arrhythmias
  • ICU admission criteria:

    • QRS >100 ms
    • Arrhythmias
    • Hypotension
    • Altered mental status
    • Respiratory depression
    • Seizures

Important Caveats and Pitfalls

  1. Do not rely on plasma drug levels to guide management; clinical presentation is more important 2

  2. Do not underestimate "low-dose" overdoses - even amounts as low as 500-1000 mg can be life-threatening 5

  3. Watch for late deterioration - fatal dysrhythmias can occur late after overdose, particularly in patients who received inadequate initial treatment 2

  4. Avoid Class IA and IC antiarrhythmics as they may worsen sodium channel blockade and increase toxicity 4

  5. Monitor for QT prolongation and torsades de pointes - amitriptyline can cause TdP, especially with high doses 4

  6. Consider co-ingestions - multiple drug ingestions (including alcohol) are common in deliberate tricyclic antidepressant overdose 2

By following this structured approach with early recognition and aggressive management of cardiac toxicity with sodium bicarbonate, outcomes can be significantly improved in amitriptyline overdose.

References

Research

Analysis of amitriptyline overdose in emergency medicine.

Emergency medicine journal : EMJ, 2011

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

A study of low-dose amitriptyline overdoses.

The American journal of psychiatry, 1977

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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