This toolbox compares pharmacologic options for treatment-resistant depression (TRD) that may be considered if the patient fails to experience adequate response or remission despite optimizing antidepressant therapy.

This toolbox compares pharmacologic options for treatment-resistant depression (TRD) that may be considered if the patient fails to experience adequate response or remission despite optimizing antidepressant therapy.

Various other pharmacologic agents (e.g. pindolol, buspirone, hormones, stimulants, inositol, atomoxetine, folic acid, gabapentin, lamotrigine, omega-3 fatty acids, herbal supplements) for use as augmentation or combination therapy in TRD have been reported in literature; however, there is limited evidence for efficacy of these agents.

Table 1.

Anti-depressant combinations1 

Adding another antidepressant from a different class

Advantages: Rapid response rates, no titration necessary, initial improvements are maintained and built upon; generally recommended if partial response was achieved with current treatment.

Disadvantages: Associated with reduced adherence, increased likelihood of adverse effects and drug interactions, higher costs.

Anti-depressant combinations1
Anti-depressant combinations1
Table 2.

Augmenting anti-depressants with other agents 13,14 

Adding a second agent that is not an antidepressant but may enhance antidepressant effects.

Advantages: Evidence that augmentation strategies convert partial responders, and even non-responders, to full remitters.

Disadvantages: Multiple medications, a broader range of treatment-emergent adverse events, higher cost of treatment.

Augmenting anti-depressants with other agents 1314
Augmenting anti-depressants with other agents 1314
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