Tricyclic antidepressants labelling

Rao et al.20 demonstrated a fluorescence polarization immunoassay for evaluating serum concentrations of tricyclic antidepressants (amitriptyline, imipramine, clomipramine, and doxepin) with respect to nonresponse, compliance, therapeutic window, and influences of age, sex, substance abuse, and toxicity. Abbott Laboratories TDx/TDxFLx Toxicology Tricyclic Assay FPIA (fluorescence polarization immunoassay) was used. This assay of 50 /uL samples contained tricyclic antidepressant antibodies raised in rabbits and fluorescein-labeled tricyclic antidepressant as a tracer. The assay was calibrated with imipramine in the range of 75 to 1000 fig/L (268 to 3571 nmol/L). Intra-assay and inter-assay coefficients of variation for internal quality control samples from the manufacturer were 4.2 and 4.7%, respectively. The limits of detection were 72,71,64, and 72 nmol/L for amitriptyline, imipramine, clomipramine, and doxepin, respectively. This high-throughput immunoassay was easy to use although amitriptyline, dosulepine, desipramine, and nortriptyline showed cross-reactivities ranging from 74 to 100%. 

There have been three randomized clinical trials and multiple case reports and open-label trials with the tricyclic antidepressants (TCAs) in PTSD, although only one study of childhood PTSD (Southwick et al., 1994) has been reported. Robert et al. (1999) reported the use of low-dose imipramine (1 mg/kg) to treat symptoms of ASD in children with burn injuries. In this study, 25 children ages 2 to 19 years were randomized to receive either chloral hydrate or imipramine for 7 days. Ten of 12 subjects receiving imipramine experienced from half to full remission of ASD symptoms, whereas 5 of 13 subjects responded to chloral hydrate. Sleep-related flashbacks and insomnia appeared to be particularly responsive to treatment. 

MAO Inhibitors and Other Antidepressants. Product literature and case reports caution against concurrent use of MAO inhibitors with tricyclic antidepressants (e.g., amitriptyline, imipramine) because severe atropinelike reactions, tremors, convulsions, hypothermia, and vascular collapse can occur. The labeling for most of these products warns that therapy with a MAO inhibitor or a tricyclic antidepressant should not be initiated until at least 7-14 days after therapy with the other drug has been discontinued. 

Nortriptyline, a drug belonging to the class of the tricyclic antidepressants, was labeled directly in one step by acylation of its secondary amino function by the acid chloride of cymantrene (Scheme 8.8) [34]. 

Cyclobenzaprine is indicated as an adjunct to rest and physical therapy for relief of muscle spasm associated with acute, painful musculoskeletal conditions. Like other tricyclic antidepressants, it is also prescribed off-label for the treatment of fibromyalgia and as a sleep aid. 

In addition to the treatment of depression, the Food and Drug Administration (FDA) has approved the (on-label) use of the antidepressants for treatment of panic disorders, obsessive-compulsive disorders, bulimia nervosa, social phobia, and generalized anxiety disorder. And although not the treatment of choice, the tricyclics are sometimes used for enuresis—bed wetting. 

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