Epidemiology

Tricyclic antidepressants (TCAs) are associated with more drug-related deaths than any other class of prescription medication. Their complex pharmacologic activity, low therapeutic index, and general availability predispose to the development of clinical toxicity. The 1997 Annual Report of the American Association of Poison Control Centers Toxic Exposure Surveillance System indicated that 1 of every 27 adult exposures to a pharmaceutical medication involved a TCA. 1 Over the past 5 years, there have been an average of 19,000 exposures and 120 associated deaths related to TCAs. However, these numbers undoubtedly underestimate the true magnitude of TCA-related drug toxicity. Most reported TCA exposures occur in young adults, with approximately 60 percent of all exposures believed to be intentional

TCAs are used primarily for the treatment of major depression. In addition, they are prescribed frequently for other psychiatric and medical conditions such as obsessive-compulsive disorder, attention-deficit disorder, panic and phobia disorders, anxiety disorders, eating disorders, chronic pain syndromes, peripheral neuropathies, nocturnal enuresis, migraine headache prophylaxis, and selected drug withdrawal therapy. There are currently eight different TCAs available in the

United States (Table 152.-1), but many more varieties are available in other countries. The five most commonly reported TCAs involved in drug exposures include amitriptyline (40 percent), imipramine (17 percent), doxepin (14 percent), nortriptyline (12 percent), and desipramine (6 percent). Two related antidepressants, maprotiline and amoxapine, have minor structural differences when compared with traditional TCAs but have similar toxicity in overdose and thus will be included in this chapter. Cyclobenzaprine (Flexeril) is a muscle relaxant that is almost structurally identical to amitriptyline but lacks antidepressant activity. It tends to have less cardiotoxicity than amitriptyline but can still produce significant central nervous system (CNS) sedation and antimuscarinic toxicity in overdose. 2 The average therapeutic dose for TCAs is highly variable. Initially, lower doses are used, followed by gradual increases until the desired therapeutic response is achieved. In addition, this process allows most patients to become acclimated to the typical TCA-induced adverse effects such as CNS sedation and dry mucous membranes.

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