Dual-Action Antidepressants in the Treatment of Depression
Since the late 1980s, with the introduction of fluoxetine, the first selective serotonin reuptake inhibitor (SSRI) antidepressant, the treatment of depression has become much more of a commonplace phenomenon. The SSRIs' efficacy, side-effect profile, and safety allowed the pharmacologic treatment of depression to take a huge leap. Because of the ease of prescribing these agents and their wide therapeutic index, nonpsychiatric practitioners increasingly began to utilize them in the treatment of depression in primary care settings.

However, it quickly became apparent that the SSRIs were not a panacea for the treatment of depression. As much as 30% to 40% of patients did not respond to these agents, and many responders never did achieve full remission of their depressive symptoms. Onset of action continued to be slow, with at least 3-4 weeks needed to assess if the medication would be effective. SSRIs were not free of side effects, with sexual dysfunction, gastrointestinal effects, and increased anxiety commonplace complaints from patients.