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Cyclic antidepressants inhibit reuptake of norepinephrine and serotonin, block sodium channels, and antagonize postsynaptic serotonin receptors. They can produce severe toxicity in overdose. Their use has declined as newer, safer agents have been developed.

Clinical Features

Toxicity may present with altered mental status, seizures, cardiac conduction or rhythm disturbances, hypotension, respiratory depression, and, in severe cases, coma. If serious toxicity is going to develop, it generally develops within 6 hours of the ingestion.


The diagnosis is clinical. Characteristic ECG changes include sinus tachycardia; right axis deviation of the terminal 40 ms; PR, QRS, and QT interval prolongation. Right bundle-branch block, A-V blocks, and the Brugada pattern are less common. Amoxapine can notably cause toxicity without characteristic ECG changes.

Emergency Department Care and Disposition

Care is primarily supportive.

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

  2. Consider using 1 g/kg of activated charcoal PO if no contraindications exist.

  3. Hypotension is treated with isotonic crystalloids. Norepinephrine or epinephrine is indicated if hypotension persists.

  4. Treat conduction disturbances and ventricular dysrhythmias with 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.

  5. Treat torsades de pointes with 2 g of IV magnesium sulfate.

  6. Control agitation with benzodiazepines. Avoid physostigmine.

  7. Treat seizures with benzodiazepines. Phenobarbital, starting at 10 to 15 mg/kg IV, may be required for refractory seizures.

  8. 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 serotonin/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. Priapism can be seen at therapeutic doses.

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. Consider single-dose activated charcoal if no contraindications exist.

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

  4. Treat torsades de pointes with IV magnesium sulfate or overdrive pacing.

  5. Discharge patients who remain asymptomatic for at least 6 hours, with psychiatric evaluation as ...

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