This decline in use of phenothiazines means they will likely acco

This decline in use of phenothiazines means they will likely account for increasingly fewer false positives on TCA screening assays. Figure 5 Tricyclic antidepressant assays. A) Rank of tricyclic antidepressants,

cyclobenzaprine, and quetiapine by total number of prescriptions in the United States in the time period from 1998–2007. TCAs are indicated by closed symbols, while the non-TCAs … In our own medical system, we use Inhibitors,research,lifescience,medical two different assay methods for TCA screening (Biosite Triage® and Syva Emit® serum tox™). Over the course of 24 months (January 2007 for through January 2009), we performed GC/MS analysis for the broad detection of drugs and drug metabolites on all samples that returned a positive screening result for TCA assays (109 on Triage and 15 on Syva) to determine the most likely cause of the positive

result (Additional file 1, tab U). As shown in Figure ​Figure5B,5B, 70% of the positive results were accounted for by the presence of different amitriptyline (28.2%) Inhibitors,research,lifescience,medical or cyclobenzaprine (41.9%), a centrally acting muscle relaxant that differs from amitriptyline by the presence of one double bond [64]. Other TCAs accounted for 10.5% (1 imipramine and 10 doxepin cases) of the positive screens while two phenothiazines (chlorpromazine and prochlorperazine) accounted for only 3.2% of the positive screens. Inhibitors,research,lifescience,medical Thus, TCAs only accounted for 38.7% of the most likely causes for the positive screening results in our study. The remaining Inhibitors,research,lifescience,medical positive screens (16.0% of the total) included patients whose urine showed high concentrations of venlafaxine (n = 2), carbamazepine (n = 2), topiramate (n = 1), or quetiapine (n = 1). The frequency of drugs most likely causing positive TCA screens in our sample fits well with the overall Inhibitors,research,lifescience,medical prescription trends in the United States (Figure

​(Figure5A;5A; Additional file 1, tab S) and the known cross-reactivities of the Biosite Triage and Syva EMIT assay systems. For example, the package insert for the Triage assay states that a cyclobenzaprine urine concentration of only 2000 ng/mL will produce cross-reactivity AV-951 equal to 1000 ng/mL TCAs (Additional file 1, tab R). Given the current widespread use of cyclobenzaprine in the United States (Figure ​(Figure5A)5A) [29,64], it is not surprising to encounter false positive TCA screening assay results due to the presence of this drug. The increasing use of cyclobenzaprine and quetiapine will likely result in more and more TCA positive screens resulting from these compounds [17-19,59,65], especially combined with increasing reports of intentional misuse and overdoses with quetiapine [66-68]. Previous studies have shown cross-reactivity of quetiapine (parent drug) with marketed TCA assays but did not look at quetiapine metabolites [17-19,59,65].

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