Overdose of Tricyclic Antidepressant

At a Glance

Commonly prescribed tricyclic antidepressants (TCAs) include imipramine, amitriptyline, desipramine, nortriptyline, doxepin, protriptyline, and maprotiline. Although the prescription of TCAs has decreased since the introduction of serotonin reuptake inhibitors to treat depression, overdose with TCAs can occur and may be life-threatening because of cardiotoxicity of these drugs. In addition to cardiotoxicity and potential QRS prolongation, TCA overdose can cause anticholinergic effects (e.g., flushing, dry mouth, dilated pupils, and hyperpyrexia) and central nervous system (CNS) effects (e.g., confusion and hallucinations).

What Tests Should I Request to Confirm My Clinical Dx? In addition, what follow-up tests might be useful?

In suspected TCA overdose, a serum or urine screening immunoassay designed to detect TCAs should be performed. These screening assays may produce qualitative or semi-quantitative results with the latter indicating total tricyclic concentration (parent drug + active metabolite).

If available, confirmatory techniques, such as HPLC-UV and GC/MS, can be performed to confirm the presence of a specific TCA and quantitate its concentration.

Are There Any Factors That Might Affect the Lab Results? In particular, does your patient take any medications – OTC drugs or Herbals – that might affect the lab results?

Urine and serum drug screens have limitations, including the generation of false-positive and false-negative results. TCA immunoassays are affected by structurally similar drugs, such as carbamazepine, chlorpromazine, diphenhydramine, quetiapine, cyproheptadine, and thioridazine, which can generate false-positive results. In addition, hydroxyzine and cetirizine may also interfere with fluorescence polarization immunoassays. False-negative results can be seen if a particular TCA immunoassay has low cross-reactivity for a specific TCA, such as doxepin.

Immunoassays should only be used for initial diagnosis of tricyclic antidepressant overdose and should not be used for therapeutic drug monitoring.

Other than structurally similar drugs that interfere with immunoassays, there is no report of over-the-counter (OTC) drugs or herbals that interfere with immunoassays for determining TCAs.

What Lab Results Are Absolutely Confirmatory?

Confirmatory techniques, such as HPLC-UV and GC/MS, can be performed to confirm the presence of a specific tricyclic antidepressant and quantitate its concentration. These techniques are free from any interference and should be used for confirming tricyclic overdose, as well as therapeutic drug monitoring of tricyclic antidepressants.