Overview of Currently Available Antidepressants

Abstract

Until the late 1980s when the first selective serotonin reuptake inhibitor (SSRI) was introduced, clinicians had limited options for treatment of clinical depression, with the only available antidepressants being the tricyclic antidepressants (TCAs), the monoamine oxidase inhibitors (MAOIs), and trazodone. In recent decades, antidepressant drug development has evolved from a process based on chance discovery to a rational development process that molecularly targets specific sites of action in the central nervous system. Such rational drug development has produced agents that are safer and better tolerated than the older agents such as the TCAs and the MAOIs. Currently available antidepressants have a variety of mechanism of actions. Some of them, such as the tertiary amine TCA amitriptyline, affect multiple sites of action (SOA) while others, such as the SSRIs, target a single SOA. Drugs such as venlafaxine and bupropion affect two SOAs. This chapter serves as an introduction to the chapters that follow, by reviewing the mechanisms of action of antidepressants and providing a brief overview of the history of antidepressant development. Each of the five chapters in the section that follows deals with different groups of antidepressants. The next chapter and the one following it cover the first classes of antidepressants that were introduced, the TCAs and the MAOIs, respectively. Newer antidepressants are then reviewed: the SSRIs and other recently developed antidepressants. Finally, Wheatley provides an overview of new findings concerning herbal agents in the treatment of depression.