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Cyclic antidepressants inhibit reuptake of norepinephrine and serotonin and antagonize postsynaptic serotonin receptors. They can produce severe toxicity in overdose.

Clinical Features

Toxicity may present with altered mental status, seizures, cardiac conduction or rhythm disturbances, hypotension, respiratory depression, and, in severe cases, coma.


ECG changes include sinus tachycardia; right axis deviation of the terminal 40 milliseconds; PR, QRS, and QT interval prolongation; right bundle-branch block; A-V blocks; and the Brugada pattern.

Emergency Department Care and Disposition

Care is primarily supportive.

  1. Obtain IV access and initiate cardiac rhythm and ECG monitoring.

  2. Patients should receive 1 gram/kilogram of activated charcoal PO. This may be preceded by gastric lavage in patients presenting < 1 hour after a large ingestion.

  3. Hypotension is treated with isotonic crystalloids. If no response, administer sodium bicarbonate as an IV bolus of 1 to 2 mEq/kg, repeated until the patient improves or until blood pH is 7.50 to 7.55. A continuous IV infusion (150 mEq added to 1 L of 5% dextrose in water) may be used at a rate of 2 to 3 mL/kg/h. Norepinephrine is indicated if hypotension persists.

  4. Treat conduction disturbances and ventricular dysrhythmias with sodium bicarbonate. Synchronized cardioversion may be indicated for unstable patients. Treat torsades de pointes with 2 grams of IV magnesium sulfate.

  5. Control agitation with benzodiazepines.

  6. Treat seizures with benzodiazepines. Phenobarbital, starting at 15 milligrams/kilogram IV, may be required for refractory seizures.

  7. Patients who remain asymptomatic after 6 hours do not need admission for toxicologic reasons. Admit symptomatic patients to a monitored bed or intensive care unit (ICU).

Newer antidepressants include trazodone, bupropion, mirtazapine, selective serotonin reuptake inhibitors, and serotononin/norepinephrine reuptake inhibitors. They are safer than older agents but can still cause toxicity, including the serotonin syndrome.

Clinical Features

Symptoms of toxicity include central nervous system depression, ataxia, dizziness, seizures, orthostatic hypotension, vomiting, and abdominal pain. ECG abnormalities include QT interval prolongation, sinus bradycardia and tachycardia, and torsades de pointes.

Emergency Department Care and Disposition

Supportive care is generally sufficient in isolated overdoses.

  1. Initiate cardiac rhythm monitoring and obtain a 12-lead ECG.

  2. Single-dose activated charcoal is recommended. Gastric lavage followed by activated charcoal may be beneficial for trazodone ingestions >2 grams if early after ingestion.

  3. Treat hypotension with isotonic IV fluids, followed by norepinephrine.

  4. Treat torsades de pointes with IV magnesium sulfate.

  5. Discharge patients who remain asymptomatic for at least 6 hours, with psychiatric evaluation as indicated. Admit those with neurologic and/or cardiac symptoms for >6 hours after ingestion to a monitored bed.

Clinical Features

Toxicity manifests as agitation, dizziness, tremor, vomiting, drowsiness, and tachycardia. Seizures are more common than with other atypical antidepressants. ...

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