Has Deep Brain Stimulation Shown Its Full Potential in Treatment-Resistant Depression? A Scoping Review

Major depressive disorder is increasingly conceptualized as a networkopathy involving dysfunction across brain networks rather than isolated regions. This perspective has supported the use of deep brain stimulation (DBS) in treatment-resistant depression (TRD), where conventional therapies have failed. In this scoping review, we examined peer-reviewed studies on bilateral DBS for TRD, with a focus on the relationship between stimulation targets, conceptual frameworks of depression, and clinical outcome measures. A comprehensive literature search was conducted in September 2024 across 6 bibliographic databases, supplemented by citation tracking strategies to identify additional relevant studies. Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines, we screened and selected studies based on predefined eligibility criteria. The review identified significant variability in how TRD is defined, which brain targets are selected, and how these are associated with specific symptom dimensions. Anatomical targets varied widely, reflecting differing neurobiological rationales. While most studies assessed symptom severity using standardized scales such as the Montgomery-Åsberg Depression Rating Scale or Hamilton Depression Rating Scale, a minority of studies (8 of 48 [16.7%]) did not specify which symptom dimensions were expected to respond to DBS. Despite methodological heterogeneity, DBS appears promising for symptom alleviation in TRD. However, its clinical benefits remain to be fully established. The review highlights the need for greater standardization, including consistent definitions of TRD, clear symptom mapping, and improved integration of patient-reported and functional outcomes. Although most existing studies focus on bilateral stimulation, future work should also explore unilateral and multitarget approaches to advance toward more personalized neuromodulation strategies.