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This is a clinician-written, evidence-based summary aligned to the 2026 MLA Content Map. It is intended for medical students and junior doctors preparing for the UKMLA. Always cross-reference with NICE guidance, local protocols, and clinical judgement.
Key points
- TCAs (amitriptyline, dosulepin, nortriptyline) are highly toxic in overdose — lethal dose as low as 10–20 mg/kg
- Three main toxicity mechanisms: anticholinergic effects, sodium channel blockade (cardiac), alpha-adrenergic blockade (hypotension)
- ECG: wide QRS (>100 ms) = cardiac sodium channel blockade → risk of VT/VF
- First-line for cardiac toxicity: IV sodium bicarbonate 8.4% (50–100 mL) — narrows QRS and treats acidosis
- Seizures: IV benzodiazepines (lorazepam/diazepam). Do NOT give phenytoin (worsens cardiac toxicity)
Overview
Tricyclic antidepressant overdose is one of the most dangerous drug overdoses due to narrow therapeutic index and multiple toxicity mechanisms. TCAs block cardiac sodium channels (causing conduction delays and arrhythmias), block muscarinic receptors (anticholinergic effects), block alpha-1 adrenoceptors (hypotension), and block histamine H1 receptors (sedation). The combination of seizures, arrhythmias, and coma makes TCA overdose rapidly fatal. IV sodium bicarbonate is the cornerstone of treatment for cardiac toxicity — it increases serum pH (reducing TCA binding to sodium channels) and provides a sodium load that helps overcome the sodium channel blockade.
Epidemiology
Despite decreasing prescribing of TCAs as first-line antidepressants, they remain a significant cause of overdose deaths. Amitriptyline is the most commonly prescribed TCA in the UK (often for chronic pain and migraine prophylaxis rather than depression). Dosulepin is the most dangerous TCA in overdose. Ingestion of >10 mg/kg body weight is potentially serious; >20 mg/kg is potentially life-threatening.
Clinical Features
Symptoms
Anticholinergic syndrome: dry mouth, blurred vision, urinary retention, confusion, agitation, hallucinations
Drowsiness progressing rapidly to coma
Seizures
Signs
Dilated pupils (mydriasis) — unlike opioid overdose which has miosis
Tachycardia (anticholinergic effect)
Hypotension (alpha-1 blockade)
Wide QRS complex on ECG (>100 ms) — indicates sodium channel blockade
Prolonged QT interval
Seizures (may be first presentation)
Arrhythmias: VT, VF, torsades de pointes
Hyperthermia (from anticholinergic effect)
Absent bowel sounds (ileus from anticholinergic effect)
Investigations
First-line
12-lead ECG (URGENT)QRS >100 ms = significant sodium channel blockade. QRS >160 ms = high risk of arrhythmias. Also check QTc
VBG/ABGMetabolic acidosis worsens TCA toxicity (increases free drug binding to sodium channels) — must correct
Blood glucoseExclude hypoglycaemia
Second-line
U&EsPotassium (arrhythmia risk), renal function
Paracetamol and salicylate levelsExclude co-ingestion
Specialist
Continuous cardiac monitoringMinimum 12 hours — arrhythmias can develop late
1
Immediate
- ABCDE approach — intubate early if GCS dropping rapidly
- Activated charcoal 50 g if <1 hour since ingestion and airway protected
- Continuous cardiac monitoring for minimum 12 hours
- IV access and fluid resuscitation for hypotension
2
Cardiac toxicity (QRS >100 ms)
- IV sodium bicarbonate 8.4% — 50–100 mL bolus (1–2 mmol/kg)
- Aim to narrow QRS to <100 ms and maintain arterial pH 7.45–7.55
- Repeat sodium bicarbonate as needed
- If refractory VT/VF: IV magnesium, consider IV lipid emulsion (Intralipid 20%)
3
Seizures
- IV lorazepam 4 mg or diazepam 10–20 mg
- Do NOT use phenytoin — worsens cardiac conduction block
- Correct acidosis (seizures worsen acidosis which worsens cardiac toxicity — vicious cycle)
4
Hypotension
- IV crystalloid boluses first
- If refractory: noradrenaline infusion (alpha-agonist counteracts alpha-blockade)
- Avoid flumazenil even if benzodiazepine co-ingestion suspected (lowers seizure threshold)
Complications
- Cardiac arrest: VT/VF from sodium channel blockade — can occur rapidly
- Status epilepticus: Worsens acidosis which worsens cardiac toxicity
- Aspiration pneumonia: From seizures and reduced consciousness
- Rhabdomyolysis: From prolonged seizures or immobility
UKMLA Exam Tips
- 1Wide QRS (>100 ms) + anticholinergic features + seizures = TCA overdose
- 2IV sodium bicarbonate 8.4% is the KEY treatment for cardiac toxicity — narrows QRS and corrects acidosis
- 3Do NOT give phenytoin for TCA-induced seizures — it worsens sodium channel blockade
- 4TCA overdose has DILATED pupils (anticholinergic). Opioid overdose has PINPOINT pupils
- 5Anticholinergic toxidrome: "hot as a hare, dry as a bone, red as a beet, blind as a bat, mad as a hatter"
- 6Dosulepin is the most dangerous TCA in overdose — higher fatality rate per prescription than other TCAs
- 7Acidosis worsens TCA toxicity — always correct pH with sodium bicarbonate
practicetest your knowledge on TCA OverdoseApply what you've learnt with UKMLA-style questions from the iatroX Q-Bank — Clinical Pharmacology and beyond.
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