Tricyclic Antidepressant - Overdose

Overdose

TCA overdose is a significant cause of fatal drug poisoning. The severe morbidity and mortality associated with these drugs is well documented due to their cardiovascular and neurological toxicity. Additionally, it is a serious problem in the pediatric population due to their inherent toxicity and the availability of these in the home when prescribed for bed wetting and depression.

A number of treatments are effective in a TCA overdose.

An overdose on TCA is especially fatal as they are rapidly absorbed from GI tract in the alkaline conditions of the small intestines. As a result, toxicity often becomes apparent in the first hour after an overdose. However, symptoms may take several hours to appear if a mixed overdose has caused delayed gastric emptying

Many of the initial signs are those associated to the anticholinergic effects of TCAs such as dry mouth, blurred vision, urinary retention, constipation, dizziness, and emesis (or vomiting). Due to the location of norepinephrine receptors all over the body, many physical signs are also associated with a TCA overdose:

1. Anticholinergic effects: altered mental status (e.g., agitation, confusion, lethargy, etc.), resting sinus tachycardia, dry mouth, mydriasis (pupil dilation), fever
2. Cardiac effects: hypertension (early and transient, should not be treated), tachycardia, orthostasis and hypotension, arrhythmias (including ventricular tachycardia and ventricular fibrillation, most serious consequence) / ECG changes (prolonged QRS, QT, and PR intervals)
3. CNS effects: syncope, seizure, coma, myoclonus, hyperreflexia
4. Pulmonary effects: hypoventilation resulting from CNS depression
5. Gastrointestinal effects: decreased or absent bowel sounds

Treatment depends on severity of symptoms. If there is a metabolic acidosis, infusion of sodium bicarbonate is recommended by Toxbase (UK poisons advice website). Two mechanisms are postulated for its therapeutic effect. Tricyclics are protein bound and become less bound in more acidic conditions. By reversing the acidosis, protein binding increases and bioavailability thus decreases. An alternative explanation is that the sodium load helps to reverse the Na+ channel blocking effects of the TCA. Treatment is otherwise supportive.