**5. Conclusions**

While enthusiasm for DBS as a therapy for TRD has been tempered by recent randomized trials, this meta-analysis reveals that active stimulation significantly ameliorates depression in patients with TRD. The meta-regression did not reveal an optimal stimulation target to treat depression due to the small size and number of available studies, and also likely due to the heterogeneous nature of this condition's neurobiology. Additional trials are needed to determine optimal stimulation targets. Further studies are also required to establish the patient populations for whom DBS would be effective. Particular attention to factors that include electrode placement technique, patient selection, and long-term observation is essential for future trial design.

**Supplementary Materials:** The following are available online at http://www.mdpi.com/2077-0383/9/9/2796/s1, Table S1: Complete list of adverse events.

**Author Contributions:** Conceptualization, F.L.H. and G.H.B.; methodology, F.L.H.; validation, F.L.H., A.I.Y., M.A.C., G.H.B.; formal analysis, F.L.H and A.I.Y; investigation, F.L.H.; data curation, F.L.H.; writing—Original draft preparation, F.L.H. and A.I.Y.; writing—Review and editing, F.L.H., A.I.Y., M.A.C., G.H.B.; visualization, F.L.H.; supervision, G.H.B.; project administration, G.H.B. All authors have read and agreed to the published version of the manuscript.

**Funding:** This research received no external funding.

**Conflicts of Interest:** The authors declare no conflict of interest.
