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. Author manuscript; available in PMC: 2015 May 7.
Published in final edited form as: Focus (Am Psychiatr Publ). 2010 Fall;8(4):488–500. doi: 10.1176/foc.8.4.foc488

Table 2. Developing Treatment Options for TRD.

Approach Highest Level of Support Comments
Dopamine agonists Two placebo-controlled RCTs
CRF-1 receptor antagonists Open-label data One negative placebo-controlled RCT has been published
Glucocorticoid receptor antagonists One placebo-controlled RCT for mifepristone Study was done in patients with psychotic depression; benefits were greater for psychotic than depressive symptoms
Substance P receptor antagonists Two placebo-controlled RCTs for aprepitant Open-label data for 2 other agents The smaller RCT was positive, but the larger phase III study was negative
Ketamine Two placebo-controlled RCTs Effects are acute (within a few hours), but relapse generally occurs within a few days
Riluzole Open-label studies
Scopolamine Two placebo-controlled RCTs
SAMe One placebo-controlled RCT
VNS Three long-term open-label studies A 10-week sham-controlled RCT was negative; data from one long-term open-label study were compared with those from a nonrandomized, treatment-as-usual group followed for a similar period of time
TMS Several sham-controlled RCTs Data from a large, industry-sponsored RCT suggest no statistically significant antidepressant effect for TMS in patients in whom more than one adequate antidepressant medication has failed
MST Open-label comparisons to ECT One study suggested greater antidepressant efficacy for ECT over MST
tDCS Three sham-controlled RCTs Two of the three RCTs were positive; one was negative
DCS One open-label study
DBS One open-label study for each of 3 targets (SCC, VC/VS, and NAcc)Single case reports for 2 other targets (ITP and habenula)

RCT, randomized controlled trial; SCC, subcallosal cingulate; VC/VS, ventral capsule/ventral striatum; NAcc, nucleus accumbens; ITP, inferior thalamic peduncle.