Tricyclic Antidepressants

Cause multiple receptor effects (sodium, potassium, and calcium channels, muscarinic and alpha-receptor blockades, some sympathetic agonist effects). At higher doses sodium channel blockade predominates and can be lethal.
Large volume of distribution, liver metabolism with enterohepatic circulation.
The main toxic effects are usually apparent within 4 hours of ingestion:
- CNS depression, irritation and convulsions.
- Anticholinergic effects.
- Tachycardia first, arrhythmias next, then progression to cardiovascular depression.
  Note: After initial tachycardia, the main cardiac effects are slowing of conduction and hence widening of all phases of the ECG, cardiovascular depression, bradyarrhythmia and escape rhythms.
Treatment depends on the dose taken, the time taken and the symptoms displayed.


Effects of tricyclic antidepressant overdosage
Dose	Effect
<5 mg/kg	Minimal symptoms
5-10 mg/kg	Drowsiness and mild anticholinergic symptoms
>10 mg/kg	Potential for coma, hypotension, seizures and arrhythmias within 2-4 hrs
>30 mg/kg	Life-threatening toxicity with pH dependent cardiotoxicity and coma.

Sodium bicarbonate has both prophylactic and therapeutic effects on cardiac toxicity for two possible reasons. Alkalinization of the blood to a pH of 7.5 seems to be cardio-protective. Sodium bicarbonate also provides a bolus of sodium that may reduce the cardiotoxicity caused by sodium channel blockade. Give 50-100 mmol sodium bicarbonate IV over 5-10 minutes. Improvement may be apparent within minutes.
If intubated for airway management then hyperventilation will help by raising the blood pH.
Suxamethonium may raise parasympathetic tone which can increase heart block, however its use may be unavoidable if urgent airway management is required.
Treat convulsions with benzodiazepines if required.
Many arrhythmias will respond to bolus bicarbonate as above. All drugs that prolong depolarization are contraindicated.
Lignocaine 1.5 mg/kg by IV bolus is considered the next line of treatment. Magnesium may be considered. Pacing, cardioversion and defibrillation are relatively safe but unlikely to be effective.
Hypotension can be treated with IV fluid boluses and bicarbonate. If persistently hypotensive then vasopressors such as adrenaline or noradrenaline can be infused.
Patients with a widened QRS or any altered level of consciousness should be referred to ICU.
Patients who have no signs or symptoms at 6 hours post ingestion can be discharged after a mental health assessment.


Information about this CDHB document (1585):
Document Owner:	Blue Book Editorial Committee (see Who's Who)
Issue Date:	December 2013
Next Review:	December 2015
Keywords:
Note: Only the electronic version is controlled. Once printed, this is no longer a controlled document.
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Topic Code: 1585