*Article* **Deep Brain Stimulation Is E** ff**ective for Treatment-Resistant Depression: A Meta-Analysis and Meta-Regression**

### **Frederick L. Hitti 1,\*, Andrew I. Yang 1, Mario A. Cristancho 2 and Gordon H. Baltuch 1**


Received: 21 July 2020; Accepted: 27 August 2020; Published: 30 August 2020

**Abstract:** Major depressive disorder (MDD) is a leading cause of disability and a significant cause of mortality worldwide. Approximately 30–40% of patients fail to achieve clinical remission with available pharmacological treatments, a clinical course termed treatment-resistant depression (TRD). Numerous studies have investigated deep brain stimulation (DBS) as a therapy for TRD. We performed a meta-analysis to determine e fficacy and a meta-regression to compare stimulation targets. We identified and screened 1397 studies. We included 125 citations in the qualitative review and considered 26 for quantitative analysis. Only blinded studies that compared active DBS to sham stimulation (k = 12) were included in the meta-analysis. The random-e ffects model supported the e fficacy of DBS for TRD (standardized mean di fference = −0.75, <0 favors active stimulation; *p* = 0.0001). The meta-regression did not demonstrate a statistically significant di fference between stimulation targets (*p* = 0.45). While enthusiasm for DBS treatment of TRD has been tempered by recent randomized trials, this meta-analysis reveals a significant e ffect of DBS for the treatment of TRD. Additionally, the majority of trials have demonstrated the safety and e fficacy of DBS for this indication. Further trials are required to determine the optimal stimulation parameters and patient populations for which DBS would be e ffective. Particular attention to factors including electrode placement technique, patient selection, and long-term follow-up is essential for future trial design.

**Keywords:** deep brain stimulation; treatment-resistant depression; depression; meta-analysis; meta-regression; subcallosal cingulate gyrus; medial forebrain bundle; inferior thalamic peduncle; ventral capsule; ventral striatum
