Antidepressant effectiveness in severe depression and melancholia.

While outcome has improved in patients with depressive disorders since the introduction of the newer antidepressants, some physicians still treat severely depressed patients with the older tricyclic antidepressants because of conflicting reports about the efficacy of the newer agents, particularly the selective serotonin reuptake inhibitors, in severe depression. However, a standardized operational definition of severe depression is lacking, and treatment studies are difficult to evaluate due to variation in methodology. Remission rates are relatively low in many of the short-term clinical trials of the newer antidepressants in severe depression, but may improve if the research design were to include a longer trial and aggressive dosing. There is some evidence that venlafaxine, a serotonin-norepinephrine antidepressant, may offer some advantage for severely depressed patients.