Current and Emerging Therapeutics of Anxiety and Stress Disorders

During the 1960s and 1970s the concept of ‘‘pharmacologic dissection’’ became popular as a putative method for differentiating among different categories of psychiatric illness. At the time, it was widely held that anxiety disorders, but not depression, respond to benzodiazepines, whereas depression, but not anxiety disorders, responds to antidepressants. Panic disorder was held to be the one exception, responding only to antidepressants. Alprazolam, selective serotonin reuptake inhibitors (SSRIs), and buspirone had not yet been tested. On the basis of these observations, it was asserted that anxiety and depression are clearly distinct categories of illness. Thirty years later we find that the situation has changed dramatically. The first inconsistency with the notion of pharmacologic dissection was the clear finding that panic disorder does indeed respond to benzodiazepines. For a while, alprazolam and then clonazepam were regarded by some authorities and clinicians as first-line therapies for panic disorder, replacing tricyclics and monoamine oxidase inhibitors. An even more potent challenge, however, has come from the evidence not only that anxiety disorders respond to antidepressants but also that antidepressants work better than benzodiazepines for most of them. As this chapter discusses, antidepressants are now considered the appropriate pharmacologic intervention for panic disorder, social anxiety disorder, posttraumatic stress disorder (PTSD), and generalized anxiety disorder (GAD). The latter case is particularly interesting. Once considered the sole domain of benzodiazepines, GAD was then shown to be responsive to a drug in an entirely new category, with no relationship whatsoever to the benzodiazepine receptor or -aminobutyric acid (GABA)—buspirone. At about the same time evidence