The Development of New Antidepressants: Focus on Duloxetine and Escitalopram.

Effective antidepressant pharmacotherapy began in the 1950s, with the introduction of tricyclic antidepressants (TCA) and monoamine oxidase inhibitors (MAOI). Unfortunately, these medications have properties that can limit their utility. TCA can produce a variety of side effects and they have a narrow therapeutic index with a high risk of death in overdose. MAOI require dietary restrictions and carry a risk of hyperadrenergic crisis. Moreover, the advent of selective serotonin reuptake inhibitors (SSRI) has significantly affected the treatment of depression. SSRI have become the first-line treatment for depression because they are effective, require minimal dose titration and have fewer side effects with less risk of death in overdose than the traditional agents. In addition, the sexual side effects of SSRI and the older antidepressants can reduce compliance and diminish patient's quality of life.