Evaluating antidepressant therapies: remission as the optimal outcome.

Depression is the fourth-largest contributor to the global burden of disease, and it causes profound suffering and extreme costs to health care systems and society. Although there have been many new antidepressants introduced, few depressed individuals receive the optimal treatment. One problem is that the traditional definition of response to antidepressant therapy, i.e., a 50% improvement in symptoms, ensures little beyond a reduction of syndromal intensity. Responders who have persistent depressive symptoms experience ongoing psychosocial dysfunction, poorer health, and an increased risk of relapse. The goal of the first or acute-phase treatment should be complete remission of symptoms and a full return to premorbid levels of functioning. Remission is also a necessary, transitional state toward sustained recovery. Within this context, evidence pertaining to various treatment approaches is reexamined, taking into account critical methodological issues such as design sensitivity and statistical power. Whereas results of individual studies are inconsistent, the findings of meta-analyses (i.e., quantitative and pooled) suggest that both psychotherapy-pharmacotherapy combinations and use of antidepressants that enhance serotonergic and noradrenergic neurotransmission increase the likelihood of remission.