This document discusses tricyclic antidepressant (TCA) toxicity from overdose or drug interactions. It outlines the clinical features and timeline of TCA toxicity, which include early anticholinergic effects followed later by myocardial depression, seizures, and arrhythmias. Diagnostic testing includes ECG and urine drug screens. Management involves stabilizing the patient, administering activated charcoal, fluid resuscitation, vasopressors if hypotensive, benzodiazepines for seizures, and other interventions depending on symptoms. Patients exhibiting signs of TCA toxicity such as arrhythmias or seizures require ICU admission.

2. Toxicology
Dr. M.M. Shater
TRICYCLIC ANTIDEPRESSANTS
ROSEN’S
EMERGENCY MEDICINE
Concepts and Clinical Practice

3. Principles of Toxicity
 In the 1950s, imipramine became the first TCA used for the treatment of
depression.
 use for other conditions, including treatment of migraines, various neuropathies,
trigeminal neuralgia, and nocturnal enuresis has increased.

4. Clinical Features
 Cyclic antidepressant toxicity can result from overdose of a TCA or drug
interactions.
 Cytochrome P450
 Desipramine and nortriptyline
 serotonin syndrome(MAOI or SSRI)

5. Clinical Features
 After an overdose of a TCA, symptoms typically begin within 1 to 2 hours.
 within the first 2 hours:
 anticholinergic effects(dry mucosal membranes, urinary retention, and hot, dry
skin)
 Pupils are often small
 Patients may be alert and confused, severely agitated, mute, hallucinating, or
even deeply comatose
 Speech is often rapid and mumbling in character
 Seizures
 Early hypertension , hypotension may also be due

6. Clinical Features
 Later (2 to 6 hours post ingestion):
 myocardial depression
 hypotension and bradycardia
 widening of the QRS interval(prognostic):100 , 160 msec
 prolonged QT interval
 Severe: depressed level of consciousness, seizures, hypotension, and wide-
complex cardiac arrhythmias.

7. Clinical Features
 Chronic toxicity:
 Confusion, urinary retention, and prolonged corrected QT (QTc) interval are
common.

8. Differential Diagnoses
 Diphenhydramine and carbamazepine
 Cocaine
 serotonin syndrome
 procainamide, disopyramide, quinidine
 flecainide, encainide, and propafenone
 Propoxyphene and propranolol
 amantadine, mesoridazine, and thioridazine.

9. Key
 The constellation of early anticholinergic symptoms, decreased level of
consciousness followed by seizures, wide QRS, and cardiovascular collapse is
highly suggestive of acute TCA overdose.

10. Diagnostic Testing
 ECG:
 sinus tachycardia
 (aVR) demonstrating tall R wave
 QT prolongation
 Urine drug of abuse screens commonly test for the presence of TCAs, but a
positive test result suggests only use of a TCA or another xenobiotic that cross-
reacts with the screen.
 Urine drug of abuse screens commonly test for the presence of TCAs, but a
positive test result suggests only use of a TCA or another xenobiotic that cross-
reacts with the screen

11. Management
 Ensuring stability of the airway, with adequate ventilation, and volume repletion
are of primary importance.
 activated charcoal
 Patients with sinus tachycardia alone do not need specific treatment but should
be monitored to detect QRS widening early in the clinical course.
 Early hypertension should not be treated
 Hypotensive patients should first receive fluid resuscitation with an isotonic
crystalloid. Patients who remain hypotensive should be treated with direct-acting
vasopressors such as norepinephrine and epinephrine.

12. Management
 Hypertonic sodium bicarbonate
 Class Ia or Ic antidysrhythmics should be avoided.
 Seizures are best treated with an IV benzodiazepine
 Refractory seizures can be treated with phenobarbital
 Acidosis and intubation
 Physostigmine
 Intravenous lipid emulsion (ILE)

13. Disposition
 If the heart rate has not exceeded 100/minute for a period of at least 10 minutes,
ECG intervals are normal, level of consciousness is normal, and no seizures have
developed within 6 hours of a TCA overdose, it is unlikely that toxicity will occur.
The patient can be medically cleared from the emergency department for
psychiatric evaluation and disposition if needed.
 Patients with signs of cyclic antidepressant cardiotoxicity, seizures, or coma
should be admitted to an intensive care unit.