Laboratory Studies
As in all patients with potential overdose, the following should be routinely monitored in cases of cyclic antidepressant (CA) poisoning:
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Complete blood cell count (CBC)
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Serum acetaminophen level
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Electrolyte levels (with determination of anion gap)
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Urinalysis (UA)
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Urine or serum pregnancy test (in females of childbearing age)
Arterial blood gas (ABG) testing is also indicated. Cyclic antidepressant toxicity usually results in mixed acidosis due to respiratory depression coupled with hypotension from myocardial depression and peripheral vasodilation, thus resulting in increased lactate production. Acidemia decreases protein binding and increases plasma levels of free drug. Therefore, correction of pH is a primary target of therapy in cyclic antidepressant overdose.
In addition to serum acetaminophen levels, obtaining serum salicylate levels can also be considered. Further serum and/or urine toxicology screening for other potential co-ingestants (eg, ethanol) may be performed if indicated based on the clinical picture. Urine drug screens should not be routeinly obtained as they do not change clinical management. Serum and urine cyclic antidepressant screens are available but are notorious for false positives, including from cyclobenzaprine and diphenhydramine, and have not been shown to have clinical utility. [31]
Serum cyclic antidepressant level
Serum cyclic antidepressant levels are typically available through reference and research laboratories only, and thus are not available for at least several days, well after the peak of toxicity. Therefore, levels may only be used to retrospectively confirm suspected poisoning or give a rough estimate of overdose.
However, serum levels do not correlate with toxic effects. This is due to the highly lipophilic nature of cyclic antidepressants and high degree of protein binding. Because of the large volume of distribution, tissue levels of cyclic antidepressant are often much higher than serum levels of free drug.
In fact, a meta-analysis of 18 studies of prognostic indicators in cyclic antidepressant overdose found that prolongation of the QRS interval on the electrocardiogram had pooled sensitivity and specificity similar to that of serum cyclic antidepressant concentrations in predicting dysrhythmias, seizures, and death. Both measures had relatively poor predictive performance, however. [11]
Imaging Studies
Chest radiography should be performed if a history or suspicion of aspiration is noted or to rule out other causes of fever, hypotension, or respiratory failure.
Neuroimaging should also be considered for patients with altered mental status, especially if the history is unclear or if trauma is a potential comorbid contributor.
Electrocardiography
An electrocardiogram (ECG) is useful as both a screening tool for cyclic antidepressant exposure and as a prognostic indicator in cyclic antidepressant poisoning. [12] See the image below.
Toxicity, antidepressant. ECG shows the terminal R wave in aVR and the widened QRS complex associated with tricyclic antidepressant (TCA) toxicity.
The most common ECG finding in cyclic antidepressant poisoning is sinus tachycardia, usually due to peripheral antimuscarinic effects. Early ECG changes that suggest significant, evolving toxicity include prolongation of the QRS complex and QT interval; terminal 40-millisecond (msec) right-axis deviation of the QRS in aVR; and the Brugada pattern, including right bundle branch block (RBBB) and a downsloping ST segment elevation in V1-V3. Later ECG changes can include atrioventricular (AV) blocks, ectopy, and ventricular dysrhythmias.
Cyclic antidepressants block fast sodium channels in the myocardium and slow phase zero depolarization of the action potential. Ventricular depolarization is delayed, which leads to a prolonged QRS interval. QRS interval is evaluated best using the limb leads.
Widening of the QRS complex is associated with the development of seizures and dysrhythmias, and QRS duration in the limb leads can be used to assess the severity of cyclic antidepressant toxicity. Patients with a QRS of less than 100 msec are unlikely to develop seizures and dysrhythmias. When the QRS is more than 100 msec, patients have a 34% chance of seizure and a 14% chance of serious dysrhythmia. Patients with QRS complexes of more than 160 msec have a 50% chance of developing ventricular dysrhythmias.
Cyclic antidepressants affect the right fascicle of the heart. The reason is unknown, but the effect can be observed as an exaggerated height of the R wave in aVR. A large R wave in aVR is a highly sensitive screening tool for cyclic antidepressant exposure. Liebelt et al found that the finding of a large R wave in aVR had better test characteristics than any particular QRS length. In this study, an R wave of more than 3 mm in aVR was 81% sensitive and 73% specific for the development of seizures and dysrhythmias. [13]
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Toxicity, antidepressant. ECG shows the terminal R wave in aVR and the widened QRS complex associated with tricyclic antidepressant (TCA) toxicity.
