Augmentation and combination strategies in treatment-resistant depression

A substantial proportion of depressed patients show only partial or no resp onse to antidepressants, and even among responders to antidepressant treatm ent, residual symptoms are rather common. When depressions do not respond a dequately to treatment with an antidepressant, clinicians may choose to kee p the same antidepressant and add another "augmenting" compound. Such augme ntation strategies involve the use of a pharmacologic agent that is not con sidered to be a standard antidepressant but may boost or enhance the effect of an antidepressant. Alternatively, clinicians may choose combination str ategies, in which they combine the antidepressant that did not produce adeq uate response with another antidepressant, typically of a different class. There are only a few controlled clinical trials of these 2 strategies among patients with treatment-resistant depression or among patients who have on ly partially benefited from antidepressant treatment. Most of the time, cli nicians' decisions are, therefore, guided by anecdotal reports, case series , and by some relatively smaller, uncontrolled clinical trials. These augme ntation and combination strategies appear to be relatively safe and effecti ve approaches to treatment-resistant depressions, although there is a relat ive paucity of controlled studies to support their efficacy. These strategi es typically aim at obtaining a different neurochemical effect than the one obtained with the antidepressant that has not produced adequate response. While drug-drug interactions may limit the use of some of these strategies, the potential loss of partial benefit from the failed drug inherent in swi tching may increase the acceptability of augmentation and combination strat egies among partial responders. Further studies are clearly needed to evalu ate the comparative efficacy and tolerability of these different approaches in treatment-resistant depressions.