Pharmacological Strategies in the Treatment of Resistant Depression (TRD): The Past, the Present, and the Future

Friday, April 6: 3:30 PM  - 4:30 PM 
Jerilyn Ross Lecture 
Mezzanine Level 
Room: Thurgood Marshall Ballroom 
In major depressive disorder (MDD), a substantial proportion of depressed patients show only partial or no response to standard antidepressant therapies, and, even among responders to antidepressant treatment, residual symptoms are rather common. When patients with MDD do not respond adequately to treatment with an antidepressant, clinicians are faced by critical clinical decisions. The typical pharmacological strategies for treatment resistant depression (TRD) are switching to a different antidepressant, or using a pharmacologic agent that is not considered to be a standard antidepressant to boost the effect of an antidepressant that is continued (augmentation), or combining the antidepressant that did not produce adequate response with another antidepressant, typically of a different class (combination). Augmentation strategies of variable efficacy dominated the TRD literature in the early years, partly because of the modest differences in efficacy across antidepressant classes. More recently, there has been an emergence in practice of switching and combination strategies, reflecting the introduction of antidepressant compounds with marked differences in both efficacy and tolerability from standard therapies. In particular, with respect to the augmentation and combination strategies, there are a number of placebo-controlled clinical among patients with treatment-resistant depression, showing the efficacy of various pharmacological tactics. The best studied augmentation strategies involve the use of atypical antipsychotic agents, ketamine and other glutamergic compounds, dopaminergic agents, anti-inflammatory psychotropic drugs, and opioid modulators. The best studied combination strategies involve the use of SSRIs or SNRIs with bupropion or mirtazapine. On the other hand, clinicians' decisions are often guided also by anecdotal reports, case series, and by some relatively smaller, uncontrolled clinical trials. All these augmentation and combination strategies appear to be relatively safe and effective approaches to treatment-resistant depressions. 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.

Learning Objectives

1. Participants will learn about the typical pharmacological strategies used in the treatment of resistant depression.
2. They will also learn about the changes in approaches to resistant depression over time in both practice and research.
3. They will also become familiar with the evidence of efficacy of these various strategies. 


Maurizio Fava, MD, Massachusetts General Hospital