Tricyclic Antidepressants

Introduced in 1959, the tricyclic antidepressants (TCAs) constituted the first line of treatment for depression until the appearance of the selective serotonin reuptake inhibitors in the 1980s. The first TCA to be introduced was imipramine, which was found to have antidepressant actions instead of sedative effects that were expected based on its structure analogous to phenothiazine. Currently, there are nine TCAs (imipramine, amitriptyline, desipra-mine, nortriptyline, clomipramine, trimipramine, dox-epine, protriptyline, and amoxapine) and one tetracyclic (maprotiline) drug marketed in the United States. Central nervous system side effects are mostly due to their antimuscarinic action. Sedation, confusion, or seizures resulting from lowering of seizure threshold occur in about 15% of patients. Peripheral side effects include significant antimuscarinic effects on the cardiovascular system (arrhythmias and tachycardia) as well as blurred vision, dry mouth, constipation, and urinary retention.

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