Q. What is your opinion on employing qualitative rapid homogeneous immunoassay (enzyme-multiplied immunoassay technique, ELISA) urine screens for tricyclic antidepressant (TCA) testing in pregnant women and emergencies involving neonates, particularly at a low cutoff threshold of 300 ng/mL? Immunoassays are faster than the current practice of running a quantitative urine test using liquid chromatography-mass spectrometry (LC-MS) at a cutoff of 1,000 ng/mL. Given the sensitive nature of these cases, it is imperative that the initial testing methods detect low concentrations of TCAs, provide rapid results in emergencies, and that they are cost-effective. All presumptive TCA-positive urines would then be confirmed using serum LC-MS, which would help rule out any TCA toxicity that could impact the fetus or neonate.
A. There are several significant concerns about the use of immunoassay screens for tricyclic antidepressants.
1. Essentially all such commercial assays are known to have substantial risk for false-positives. Various publications have described high false-positive rates, which often exceed the rate of true-positives, especially as the number of prescriptions for these drugs decrease.1,2 The Association for Diagnostics and Laboratory Medicine released guidelines in January that recommend avoiding TCA immunoassays for precisely this reason. False-positives are particularly concerning for pediatric cases, as child protective services might be contacted in some scenarios based on presumptive immunoassay results before confirmation testing is done.
2. Although evidence is limited, at least one study showed urine positivity (>1,000 ng/mL) in nearly all patients taking TCAs, even when their corresponding serum demonstrated subtherapeutic or therapeutic concentrations.3 This suggests that even true-positive results might not provide clinical utility, especially for patients prescribed TCAs, and might lead clinicians to investigate toxicity when none is present. Added to this, urine can remain positive for days after last exposure to a drug, well after physiological effects have declined. This further increases the risk that a true-positive could be misleading rather than helpful.
3. While lower cutoffs are sometimes suggested for pediatric exposures to account for the small amount of drug required to cause toxicity, using such cutoffs would undoubtedly exacerbate the concerns previously described. Although confirmation testing would distinguish true- from false-positive results, it seems likely that the longer turnaround time for LC-MS testing would risk providers acting—potentially incorrectly—on the immunoassay results before the confirmation results are returned. On the other hand, if providers do not act on the immunoassay result but instead wait for confirmation to avoid a false-positive, then any time advantage for the immunoassay is lost.
In short, little is gained by performing TCA immunoassays, relative to the increased risks, even in this sensitive population.
- Tanaka T, Yoshida K, Kasai K, Yoshizumi S, Sato H. Assessment of Triage DOA, Status DS10, and Driven-Flow M8-Z on-site drug screening kits for postmortem urine. Leg Med (Tokyo). 2022;54:101993.
- Saitman A, Park HD, Fitzgerald RL. False-positive interferences of common urine drug screen immunoassays: a review. J Anal Toxicol. 2014;38(7):387–396.
- Melanson SEF, Lewandrowski EL, Griggs DA, Flood JG. Interpreting tricyclic antidepressant measurements in urine in an emergency department setting: comparison of two qualitative point-of-care urine tricyclic antidepressant drug immunoassays with quantitative serum chromatographic analysis. J Anal Toxicol. 2007;31(5):270–275.
Christine Snozek, PhD, D(ABCC)
Codirector, Clinical Chemistry and Support Services
Director, Point of Care and Central Processing
Mayo Clinic Arizona
Phoenix, Ariz.
Former Member, CAP Toxicology Committee