Deep Brain Stimulation for Refractory Depression: a Systematic Review and Meta-Analysis

Abstract

Introduction:

The burden of treatment-resistant depression (TRD) often rises in the context of large-scale crises, with catastrophic events being linked with a higher incidence of mental health issues. TRD poses a significant clinical challenge, with patients failing to achieve remission despite multiple antidepressant therapies. Deep brain stimulation (DBS) has been explored as a novel intervention, but with uncertain effectiveness and safety.

Objective:

To assess the therapeutic outcomes and tolerability of DBS in adults with TRD through a systematic review and meta-analysis.

Methods:

We systematically searched PubMed, Embase, and Cochrane CENTRAL from database inception to 17 October 2025 for studies reporting DBS outcomes in TRD. Eligible studies included randomised controlled trials and observational cohorts. The primary outcomes were changes in depression severity scores (HDRS, MADRS) and rates of response or remission. Random-effects meta-analysis was performed, with heterogeneity assessed via I². Study quality and risk of bias were appraised using Cochrane RoB 2.0.

Results:

19 out of 203 screened studies fulfilled inclusion criteria. DBS’ remarkable antidepressant effect is represented by the 14.8 point (95% CI 12.6-17.0) reduction in pooled mean MADRS, with all studies exceeding the minimum clinically important difference of ≥ 1.9 points. Age, sex, stimulation site (vALIC/NAcc, SCC, sIMFB), or depression duration (p>0.05) had no significant moderating effect, as evidenced by meta-regression. Greater improvement was predicted with longer stimulation (−0.11 MADRS points/month, p = 0.004). Across studies, substantial heterogeneity was observed (I² = 79.4%).

Conclusion:

Regardless of demographic or illness factors, DBS confers clinically meaningful antidepressant effects in TRD. However, procedural risks should be evaluated alongside benefits. Definitive predictors of response are key to guiding improving patient selection and shaping future research.