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.