While outcome has improved in patients with depressive disorders since the
introduction of the newer antidepressants, some physicians still treat seve
rely depressed patients with the older tricyclic antidepressants because of
conflicting reports about the efficacy of the newer agents, particularly t
he 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 tri
als of the newer antidepressants in severe depression, but may improve if t
he research design were to include a longer trial and aggressive dosing. Th
ere is some evidence that venlafaxine, a serotonin-norepinephrine antidepre
ssant, may offer some advantage for severely depressed patients.