Tricyclic Antidepressant Toxicity Workup

Updated: Jan 26, 2023
  • Author: Vivian Tsai, MD, MPH, FACEP; Chief Editor: David Vearrier, MD, MPH  more...
  • Print

Laboratory Studies

Studies have shown that serum cyclic antidepressant (CA) level does not correlate well with severity of CA toxicity and is a poor predictor of clinical outcome. However, because multisubstance ingestion is common, routine screening for other potentially treatable toxicants is recommended (eg, acetaminophen, aspirin). Requests for the other serum toxicologic levels should be based on the clinical picture. For example, in patients with acidosis, assess for aspirin, ethylene glycol, and methanol.

Assess the following:

  • Electrolyte, blood urea nitrogen (BUN), and creatinine levels
  • Anion gap (see the Anion Gap calculator)
  • Complete blood cell count (CBC)
  • Blood alcohol level
  • Arterial blood gases (ABGs) for evaluation of acidosis or hypoxia

Point-of-care qualitative urine immunoassays for CA are available but are of limited clinical utility. Test results are positive for most tricyclic antidepressants in the subtherapeutic-to-toxic range, with the exception of clomipramine; therefore a positive result does not imply CA toxicity. False-positive results also occur due to cross-reactivity with other polycyclic medications. A urine immunoassay may be helpful when the patient's medications are unknown and CA toxicity is suspected on the basis of history, clinical presentation, and ECG findings. [6]


Imaging Studies

Chest radiography should be performed in cases of suspected aspiration or when respiratory symptoms are noted and may be used to rule out other causes of fever, tachycardia, and altered mental status.



Electrocardiography (ECG) is a highly sensitive tool, and a normal result can be used to rule out clinically significant CA toxicity. However, ECG is not specific enough to be used alone to diagnose CA overdose. However, characteristic ECG changes can be a valuable adjunct to typical clinical features (anticholinergic toxidrome, seizures, hypotension, tachycardia) in diagnosing CA toxicity.

ECG features of CA toxicity are as follows:

  • Sinus tachycardia is the most common ECG finding in CA toxicity.

  • Measurement of QRS duration in limb leads can be used to assess the severity of CA exposure. A QRS interval greater than 100 milliseconds is the basis for treatment with bicarbonate (alkalinization).

  • Widening of the QRS complex can be used as a rough guide in determining the prognosis of TCA poisoning (eg, seizures, dysrhythmias). Patients with a QRS interval less than 100 milliseconds are unlikely to develop seizures and arrhythmias. Patients with a QRS interval greater than 100 milliseconds have up to a 34% chance of developing seizures and up to a 14% chance of developing a life-threatening cardiac arrhythmia. With a QRS complex greater than 160 milliseconds, the chance of ventricular arrhythmias increases to 50%. [7]

  • The amplitude of the R wave in lead aVR and the ratio of the R/S waves in aVR are greater in patients who developed seizures or dysrhythmias.

  • According to Liebelt et al, when the R wave in aVR equals 3 mm or more, the sensitivity and specificity for subsequent development of seizures or arrhythmias are 81% and 73%, respectively. [8]

  • ECG findings that can be observed in CA toxicity include sinus tachycardia; prolongation of the PR, QRS, and QTc intervals; nonspecific ST-segment and T-wave changes; atrioventricular block; right-axis deviation of the terminal 40-millisecond vector of the QRS complex in the frontal plane; and the Brugada pattern (downsloping ST-segment elevation in leads V1-V3 in association with right bundle branch block). [9]

  • A Brugada pattern was seen using ECG in 17% of patients with TCA toxicity in a retrospective study completed by Monteban-Kooistra et al. [10] The ECG finding abnormalities resolved after administration of sodium bicarbonate.

  • A study of 98 consecutive cases of CA intoxication in France found that the mortality rate was 6.7% among patients with the Brugada pattern and 2.4% among patients without it. However, the difference was not statistically significant (P=0.39). [11]

  • Early recognition of conduction disturbances is important in suspected CA poisoning.