Comparative benefits and harms of second-generation antidepressants: Background paper for the American College of Physicians
Major depressive disorder (MDD) is the most prevalent axis I disorder, affecting more than 16% of U.S. adults during their lifetime (1). In 2000, the economic burden of depressive disorders was an estimated $83.1 billion (2), more than 30% of which was attributable to direct medical expenses.
Pharmacotherapy dominates the medical management of MDD. Since the mid-1980s, second-generation antidepressants have gradually replaced tricyclic antidepressants and monoamine oxidase inhibitors as first-line medications, primarily because of their lower toxicity in overdose and similar general efficacy (3). These newer treatments include selective serotonin reuptake inhibitors, serotonin and norepinephrine reuptake inhibitors, selective serotonin and norepinephrine reuptake inhibitors, and other second-generation drugs (Table 1).
To date, only 2 systematic reviews have assessed the comparative efficacy and harms of second-generation antidepressants (3 - 4). These studies reported no substantial differences in efficacy or harms among agents. However, because of a lack of direct head-to-head comparisons, assessments in both studies were primarily qualitative. Consequently, uncertainties persist about the differences among the drugs for which sufficient head-to-head evidence is lacking.