Reliability of antidepressant assays: a reference laboratory perspective on antidepressant monitoring

Chromatography (gas and liquid) and immunoassays are used for monitoring the commonly prescribed tricyclic antidepressants. Many commercially available immunoassays are known to cross react with structurally similar compounds. Chromatographic methods make it possible simultaneously to resolve and quantify amitriptyline, nortriptyline, imipramine, desipramine, trimipramine, doxepin, desmethyldoxepin, protriptyline, and maprotiline-and potentially crossreactive compounds can be separated from the tricyclics. Immunoassays may have a valuable role in initial toxicological screening for the presence of a tricyclic-like compound, and they also may be helpful in a laboratory dedicated to a well-controlled patient group. However, 10% of our specimens contain more or different antidepressants than we are requested to analyze for. With our analysis, we are able to report which antidepressants are present, and in what concentrations. Further, in the case of a potential overdose of tricyclic, the primary purpose for early toxicological analysis to anticipate subsequent clinical complications. Therefore, even in the case of toxicological analysis, it is important to know exactly what tricyclic antidepressant is present rather than just the semiquantitative presence of one or more structurally related compounds, because these various compounds differ markedly in their potential for adverse effects. There are too many potential, and possibly yet unknown, interactions for a reference laboratory routinely to rely on immunoassays for therapeutic drug monitoring or toxicological identification of antidepressants.