Antidepressants are medicines primarily designed and used for depression. Recent studies have found antidepressive effects from agents not traditionally categorized as antidepressants. Many antidepressants are proved to be effective in treating conditions other than depression. Nonetheless, at this point in time, when we talk about pharmacotherapy for depression, we are still in large talking about a consensually recognized group of agents.

The categorization of antidepressants is not as systematic, with a mixed emphasis on either chemical structure or mechanism of action. Four major groups of antidepressants are – tricyclic antidepressant (TCA), monoamine oxidase inhibitor (MAOI), serotonin specific reuptake inhibitor (SSRI), and serotonin-norepinephrine reuptake inhibitor (SNRI). The first two groups were invented before the birth of fluoxetine (1989), and the latter two after. They are therefore also called “old” and “new” antidepressants, respectively. The major advantage of the new vs. old antidepressants is the decreased toxic side effects and the lethality of overdose. Tetracyclics may be considered an extension from tricyclics. There are yet other antidepressants that cannot be easily included in any of the above four major groups.

TCAs have a characteristic molecular structure that contains a 3-ring component (Figure 29–1). Mechanism wise, TCAs are either norepinephrine reuptake inhibitors or SNRIs. However, we usually reserve the term of SNRI for those newer agents that do not have the characteristic tricyclic structure.

Maprotiline and amoxapine have the similar tricyclic structure and a fourth ring attached. They are called tetracyclics. Tetracyclics are structurally and chemically very close to the tricyclic group, and are sometimes referred to, together with TCAs, as “heterocyclic antidepressants.”