Augmentation and Combination Strategies in Treatment-Resistant Depression

A substantial proportion of depressed patients show only partial or no response to antidepressants, and even among responders to antidepressant treatment, residual symptoms are rather common. When depressions do not respond adequately to treatment with an antidepressant, clinicians may choose to keep the same antidepressant and add another “augmenting” compound. Such augmentation strategies involve the use of a pharmacologic agent that is not considered to be a standard antidepressant but may boost or enhance the effect of an antidepressant. Alternatively, clinicians may choose combination strategies, in which they combine the antidepressant that did not produce adequate 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 only partially benefited from antidepressant treatment. Most of the time, clinicians’ decisions are, therefore, guided by anecdotal reports, case series, and by some relatively smaller, uncontrolled clinical trials. These augmentation and combination strategies appear to be relatively safe and effective approaches to treatment-resistant depressions, although there is a relative paucity of controlled studies to support their efficacy. These strategies 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 switching may increase the acceptability of augmentation and combination strategies among partial responders. Further studies are clearly needed to evaluate the comparative efficacy and tolerability of these different approaches in treatment-resistant depressions.