Antidepressant Toxicity Workup

Updated: Apr 12, 2015
  • Author: Jeena Jacob, MD, PharmD; Chief Editor: Asim Tarabar, MD  more...
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Laboratory Studies

Quantitative screening or tricyclic serum concentrations are of minimal utility in the acute setting because serum levels do not correlate with acute toxicity secondary to pharmacologic properties such as large volume of distribution, pH-dependent protein binding, wide intrapatient variability of terminal elimination half-lives, and prolonged distribution phases. An abbreviated screen for acetaminophen and aspirin coingestants usually is sufficient.

Electrolytes and glucose levels should be used to screen for anion gap acidosis that exists with other ingestions and to look for metabolic disturbances that can alter mental status, cause seizures, or change the ECG. See the Anion Gap calculator.

Blood gas analysis should be obtained to check pH, with an attempt to maintain an alkaline environment (pH = 7.45-7.55). Acidemia allows a greater degree of fast sodium channel binding by the TCA and produces a wider QRS on the ECG.


Imaging Studies

Obtain a chest radiograph after intubation or if evidence of hypoxia, aspiration, or ARDS is present.



See the list below:

  • Endotracheal intubation

    • Aggressively manage airway for patients who present agitated or with a decreased level of consciousness. For these patients, endotracheal intubation may be required before gastric lavage or activated charcoal to prevent aspiration.

    • Consider hyperventilation after intubation as a method of serum alkalinization. It is not as effective as sodium bicarbonate as a single method of alkalinization. If performed, carefully, monitor the patient's pH levels.

    • After the patient's airway, breathing, and circulation are secured, gastric lavage can be initiated in the symptomatic patient with an intentional overdose within 2 hours after ingestion.

    • If the patient exhibits declining mental status, the intubation should be performed first. Activated charcoal should be administered if the benefit of charcoal administration outweighs the risk of aspiration.

  • A central venous line may be helpful in administering medication and monitoring fluid status.

  • Hemodialysis

    • Hemodialysis and hemoperfusion are not effective and are not recommended for TCA poisoning.

    • The poor efficacy of hemodialysis probably is because only a small amount of free TCA is present in the serum. TCA is highly bound to serum proteins and tissues, with a large volume of distribution.



ECG has great utility in predicting the severity of toxicity. Indeed, ECG is the single most important test to determine diagnosis and prognosis. One study reported that 33% of patients with a QRS interval of 100 milliseconds or more developed seizures, and 14% developed ventricular dysrhythmias. For patients with a QRS of 160 milliseconds or more, 50% developed ventricular dysrhythmias. Other significant ECG findings include the following:

  • Prospective studies of patients with TCA overdose show that the sensitivity of an R-wave greater than or equal to 3 mm in aVR can predict toxicity.

  • Rightward deviation of QRS vector (a negative deflection in lead 1 and a positive final deflection in lead aVR) is associated with TCA toxicity.

  • Sinus tachycardia is a typical but nonspecific early sign of TCA toxicity.

  • Dysrhythmias are also nonspecific to TCA toxicity but important to respond to.

  • Ventricular tachycardia is the most common lethal dysrhythmia.

  • Torsade de pointes is uncommon in overdose but may occur in patients taking therapeutic doses.

  • Bradycardia and asystole are usually preterminal rhythms, although patients have been resuscitated from these with aggressive supportive care.