Clinical Pharmacological Evaluation of an Assay Kit for Intoxications with Tricyclic Antidepressants

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Abstract
Summary: The performance of an enzyme immunoassay kit (EMIT) to diagnose intoxications with tricyclic antidepressants was compared with a high performance liquid chromatography (HPLC) technique in vitro and in vivo. The cutoff reference solution contained in the kit of nominally 1,140 nM nortriptyline varied from 1,250 to 1,600 nM. In vitro addition of antidepressants gave positive results (change in absorbance above the cut-off value) of ˜ 1,100 nM for amitritpyline, imipramine, and desmethylimipramine and ˜ 1,600 nM for clomipramine and desmethylclomipramine. In contrast, high concentrations of the tetracyclic antidepressant maprotiline (7,000 nM) and the bicyclic zimeldine (2,000 nM) gave negative results. False positive results were obtained with high concentrations of thioridazine (4,000 nM), chlorpromazine (300 nM), and alimemazine (trimeprazine) (5,000 nM). Of 51 patient samples, five gave readings above the cutoff value, consistent with a tricyclic antidepressant intoxication, but two of these were false positives as compared with the specific HPLC analysis. However, no false negative results were obtained with the EMIT. In conclusion, the EMIT kit is likely to detect intoxications with tricyclic antidepressants but miss intoxications with nontricyclic antidepressants. For a screening method, this is a serious drawback, since maprotiline and zimeldine together make up ˜ 25% of the total of antidepressants used in Sweden. Users of the kit must also be aware that certain phenothiazines in high therapeutic doses or in intoxication cases could interfere with this test and might lead to the false diagnosis of intoxication with tricyclic antidepressants.

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