3. Principles of Toxicity
ď‚´ In the 1950s, imipramine became the first TCA used for the treatment of
depression.
ď‚´ use for other conditions, including treatment of migraines, various neuropathies,
trigeminal neuralgia, and nocturnal enuresis has increased.
4. Clinical Features
ď‚´ Cyclic antidepressant toxicity can result from overdose of a TCA or drug
interactions.
ď‚´ Cytochrome P450
ď‚´ Desipramine and nortriptyline
ď‚´ serotonin syndrome(MAOI or SSRI)
5. Clinical Features
ď‚´ After an overdose of a TCA, symptoms typically begin within 1 to 2 hours.
ď‚´ within the first 2 hours:
ď‚´ anticholinergic effects(dry mucosal membranes, urinary retention, and hot, dry
skin)
ď‚´ Pupils are often small
ď‚´ Patients may be alert and confused, severely agitated, mute, hallucinating, or
even deeply comatose
ď‚´ Speech is often rapid and mumbling in character
ď‚´ Seizures
ď‚´ Early hypertension , hypotension may also be due
6. Clinical Features
ď‚´ Later (2 to 6 hours post ingestion):
ď‚´ myocardial depression
ď‚´ hypotension and bradycardia
ď‚´ widening of the QRS interval(prognostic):100 , 160 msec
ď‚´ prolonged QT interval
ď‚´ Severe: depressed level of consciousness, seizures, hypotension, and wide-
complex cardiac arrhythmias.
7. Clinical Features
ď‚´ Chronic toxicity:
ď‚´ Confusion, urinary retention, and prolonged corrected QT (QTc) interval are
common.
8. Differential Diagnoses
ď‚´ Diphenhydramine and carbamazepine
ď‚´ Cocaine
ď‚´ serotonin syndrome
ď‚´ procainamide, disopyramide, quinidine
ď‚´ flecainide, encainide, and propafenone
ď‚´ Propoxyphene and propranolol
ď‚´ amantadine, mesoridazine, and thioridazine.
9. Key
ď‚´ 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
ď‚´ ECG:
ď‚´ sinus tachycardia
ď‚´ (aVR) demonstrating tall R wave
ď‚´ QT prolongation
ď‚´ 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.
ď‚´ 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
ď‚´ Ensuring stability of the airway, with adequate ventilation, and volume repletion
are of primary importance.
ď‚´ activated charcoal
ď‚´ Patients with sinus tachycardia alone do not need specific treatment but should
be monitored to detect QRS widening early in the clinical course.
ď‚´ Early hypertension should not be treated
ď‚´ 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
ď‚´ Hypertonic sodium bicarbonate
ď‚´ Class Ia or Ic antidysrhythmics should be avoided.
ď‚´ Seizures are best treated with an IV benzodiazepine
ď‚´ Refractory seizures can be treated with phenobarbital
ď‚´ Acidosis and intubation
ď‚´ Physostigmine
ď‚´ Intravenous lipid emulsion (ILE)
13. Disposition
ď‚´ 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.
ď‚´ Patients with signs of cyclic antidepressant cardiotoxicity, seizures, or coma
should be admitted to an intensive care unit.