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EMERGENCY

Tricyclic Antidepressant Overdose

High EvidenceUpdated: 2024-12-21

On This Page

Red Flags

  • QRS prolongation over 100ms
  • Seizures
  • Arrhythmias
  • Hypotension
  • Altered consciousness
  • Anticholinergic syndrome
Overview

Tricyclic Antidepressant Overdose

Topic Overview

Summary

Tricyclic antidepressant (TCA) overdose is a life-threatening toxicological emergency. TCAs cause sodium channel blockade (cardiac toxicity), anticholinergic effects, and alpha-adrenergic blockade (hypotension). The classic triad is altered consciousness, seizures, and cardiac dysrhythmias. QRS prolongation over 100ms is a key predictor of cardiac toxicity. Treatment is supportive with sodium bicarbonate (first-line for QRS widening and arrhythmias), benzodiazepines (seizures), and IV fluids (hypotension).

Key Facts

  • Mechanism: Sodium channel blockade + anticholinergic + alpha-blockade
  • Toxic dose: Over 10 mg/kg may be severe; over 20 mg/kg often fatal
  • Key ECG sign: QRS over 100ms predicts seizures/arrhythmias
  • Treatment: Sodium bicarbonate (first-line), benzodiazepines, IV fluids
  • Do NOT use: Flumazenil, anti-arrhythmics (class Ia/Ic), physostigmine

Clinical Pearls

QRS over 100ms = high risk of seizures; QRS over 160ms = high risk of ventricular arrhythmias

Sodium bicarbonate narrows QRS by increasing extracellular sodium and alkalinising blood

The "dirty drug" — TCAs have multiple mechanisms causing multiple toxidromes

Why This Matters Clinically

TCA overdose can deteriorate rapidly from stable to cardiac arrest. Early recognition of ECG changes and prompt treatment with sodium bicarbonate are life-saving.

Visual Summary

Visual assets to be added:

  • TCA mechanism of toxicity diagram
  • ECG showing QRS widening
  • TCA overdose management algorithm
  • Anticholinergic toxidrome features
Epidemiology

Incidence

  • Decreasing (SSRIs now more commonly prescribed)
  • Still significant mortality (~5% of severe overdoses)

Demographics

  • Deliberate self-harm (most cases)
  • Patients with depression
  • Accidental ingestion in children

Common TCAs

AgentNotes
AmitriptylineMost common in UK
Dosulepin (dothiepin)Most toxic
Imipramine
Nortriptyline
Clomipramine
Pathophysiology

Multiple Mechanisms — "Dirty Drug"

MechanismEffect
Sodium channel blockadeQRS widening, arrhythmias, negative inotropy
AnticholinergicTachycardia, mydriasis, urinary retention, delirium
Alpha-adrenergic blockadeHypotension
GABA antagonismSeizures
Potassium channel blockadeQT prolongation
Noradrenaline/serotonin reuptake inhibitionEarly tachycardia

Why Sodium Bicarbonate Works

  • Increases extracellular sodium → overcomes sodium channel blockade
  • Alkalinises blood → reduces TCA binding to sodium channels
  • Narrows QRS, treats arrhythmias
Clinical Presentation

Classic Triad

  1. Altered consciousness (ranging from agitation to coma)
  2. Seizures
  3. Cardiac dysrhythmias

Anticholinergic Features — "Hot, Dry, Blind, Mad"

Cardiovascular

Timeline

Red Flags

FindingSignificance
QRS over 100msRisk of seizures
QRS over 160msRisk of VT/VF
SeizuresGive bicarbonate and benzodiazepines
HypotensionResistant to fluids — may need vasopressor
Tachycardia
Common presentation.
Mydriasis (dilated pupils)
Common presentation.
Dry skin and mucous membranes
Common presentation.
Urinary retention
Common presentation.
Decreased bowel sounds
Common presentation.
Hyperthermia
Common presentation.
Agitation, delirium, hallucinations
Common presentation.
Clinical Examination

General

  • Altered consciousness
  • Agitation or coma

Eyes

  • Mydriasis (dilated pupils)

Cardiovascular

  • Tachycardia
  • Hypotension

Skin

  • Dry, flushed
  • Hyperthermia

Abdomen

  • Reduced bowel sounds
  • Urinary retention
Investigations

ECG — CRITICAL

FindingSignificance
Sinus tachycardiaCommon
QRS over 100msPredicts seizures
QRS over 160msPredicts ventricular arrhythmias
R wave in aVR over 3mmCorrelates with toxicity
Rightward axis of terminal 40ms
QT prolongation

Blood Tests

TestPurpose
Paracetamol, salicylateCo-ingestion
U&EBaseline
Glucose
ABGAcidosis (worsens toxicity)

TCA Levels

  • Not routinely useful (poor correlation with toxicity)
  • ECG is better predictor
Classification & Staging

By Severity

SeverityFeatures
MildAnticholinergic features only
ModerateQRS widening, drowsiness
SevereSeizures, arrhythmias, coma
Management

Initial Resuscitation

ActionDetails
AirwayProtect early if GCS reduced
Oxygen
IV access
Continuous ECG monitoringEssential
12-lead ECGAssess QRS width

Decontamination

  • Activated charcoal: Consider if within 1-2 hours and airway protected

Sodium Bicarbonate — First-Line for QRS Widening

IndicationDose
QRS over 100ms50-100 mmol IV bolus (1-2 mL/kg 8.4%)
ArrhythmiasRepeat until QRS narrows
HypotensionAlso give bicarbonate
TargetQRS under 100ms; pH 7.50-7.55

Seizures

  • IV benzodiazepines (lorazepam 4mg, diazepam 10mg)
  • Followed by sodium bicarbonate
  • Avoid phenytoin (worsens sodium channel blockade)

Hypotension

  • IV crystalloid
  • Sodium bicarbonate
  • If refractory: Noradrenaline (alpha-agonist)

Arrhythmias

  • Sodium bicarbonate (first-line)
  • Avoid: Class Ia/Ic antiarrhythmics, amiodarone
  • Consider: Lidocaine, magnesium (for TdP)
  • DC cardioversion if pulseless VT/VF

Do NOT Use

AgentReason
FlumazenilLowers seizure threshold
Class Ia/Ic antiarrhythmicsWorsen sodium channel blockade
PhysostigmineMay cause asystole

Monitoring

  • Continuous ECG for at least 6 hours
  • If asymptomatic with normal ECG at 6 hours → can discharge
Complications

Cardiac

  • Ventricular arrhythmias
  • Cardiac arrest
  • Cardiogenic shock

Neurological

  • Seizures
  • Hypoxic brain injury
  • Aspiration pneumonia

Other

  • Rhabdomyolysis
  • Hyperthermia
Prognosis & Outcomes

Prognosis

  • Good if treated early
  • Most deaths within 6 hours of ingestion
  • Prolonged CPR may be successful (TCA toxicity is reversible)

Mortality

  • Under 5% with treatment
  • Higher with delayed presentation
Evidence & Guidelines

Key Guidelines

  1. TOXBASE (UK National Poisons Information Service)
  2. AACT/EAPCCT Guidelines

Key Evidence

  • Sodium bicarbonate is effective for QRS widening and arrhythmias
  • QRS width predicts seizures and arrhythmias
Patient & Family Information

What is TCA Overdose?

Tricyclic antidepressants are older antidepressant medications. Taking too many can cause serious heart problems and fits.

Symptoms

  • Confusion
  • Fast heartbeat
  • Fits (seizures)
  • Collapse

Treatment

  • Hospital monitoring
  • Medication to protect the heart (sodium bicarbonate)
  • Medication to stop fits

Resources

  • TOXBASE
  • NHS Antidepressant Overdose
References

Key Reviews

  1. Woolf AD, et al. Tricyclic antidepressant poisoning: an evidence-based consensus guideline for out-of-hospital management. Clin Toxicol. 2007;45(3):203-233. PMID: 17453872
  2. Kerr GW, et al. Tricyclic antidepressant overdose: a review. Emerg Med J. 2001;18(4):236-241. PMID: 11435353

Guidelines

  1. TOXBASE. Tricyclic Antidepressant Poisoning Management. 2023.

Last updated: 2024-12-21

At a Glance

EvidenceHigh
Last Updated2024-12-21
Emergency Protocol

Red Flags

  • QRS prolongation over 100ms
  • Seizures
  • Arrhythmias
  • Hypotension
  • Altered consciousness
  • Anticholinergic syndrome

Clinical Pearls

  • QRS over 100ms = high risk of seizures; QRS over 160ms = high risk of ventricular arrhythmias
  • Sodium bicarbonate narrows QRS by increasing extracellular sodium and alkalinising blood
  • The "dirty drug" — TCAs have multiple mechanisms causing multiple toxidromes
  • **Visual assets to be added:**
  • - TCA mechanism of toxicity diagram

Guidelines

  • NICE Guidelines
  • BTS Guidelines
  • RCUK Guidelines