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Cyclic antidepressants were the first generation of drugs developed to treat depression. Their use for treating depression has declined greatly as safer agents have been developed. Cyclic antidepressants are now occasionally used to treat obsessive-compulsive disorder, attention-deficit/hyperactivity disorder, panic and phobia disorders, and anxiety disorders.

Cyclic antidepressants have the highest ratio of deaths to exposures for antidepressants reported to U.S. Poison Control Centers.1 Roughly half of all cyclic antidepressant exposures involve other drugs as well, and most co-ingestants increase the incidence and severity of cyclic antidepressant overdose toxicity.

Eight cyclic antidepressants are currently available in the United States (Table 177-1), with more agents available in other countries. Two related antidepressants, amoxapine and maprotiline, have structural differences from traditional cyclic antidepressants but have similar toxicity in overdose. Cyclobenzaprine is a muscle relaxant that is almost structurally identical to amitriptyline but lacks antidepressant activity, and serious toxicity from overdose is rare.2

TABLE 177-1Cyclic Antidepressants and Related Drugs

Cyclic antidepressants possess a narrow therapeutic index, and toxicity can occur at therapeutic dosages (Table 177-2).

TABLE 177-2Mechanisms for Cyclic Antidepressant Drug Toxicity at Therapeutic Dosages


The cyclic antidepressants are named after their chemical structure, which consists of a three-ring central structure plus a side chain—thus the common term tricyclic antidepressants. Maprotiline is a tetracyclic (also termed a heterocyclic), with a four-ring central structure plus a side chain. Cyclic antidepressants are subdivided into two categories: tertiary and secondary amines. Tertiary amines have two methyl groups at the end of the side chain. The five tertiary ...

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