Emerging Outlook on Personalized Neuromodulation for Depression—a Systematic Review

Introduction: There is growing evidence supporting the utility of deep brain stimulation (DBS) for treatment-resistant depression. Despite its promises, heterogeneity of clinical response in large trials has prevented DBS from becoming the mainstay treatment for treatment-resistant depression. Lack of anatomical personalization of network targets may be a reason for this heterogeneity. Tractography has been used to personalize DBS targeting and therapy. Here, we provide a systematic review of outcomes of DBS for depression comparing patients that received pre-operative tractography to those who did not.

Methods: The literature was comprehensively reviewed using Medline, EMBASE, and clinicaltrials.gov databases to August 2022. 2077 records were imported into EndNote 20, and abstracts were analyzed based on the inclusion & exclusion criteria. For each patient, pre-operative, and most recent post-operative depression scales scores (MADRS, HAM-D, BDI-II) were extracted and the percent mean improvement was calculated. Data was imported into R for statistical analysis.

Results: 19 papers—comprising of 211 patients, 36 with pre-operative tractography—met the inclusion criteria. Surgical targets included the MFB, SCC, AcB, BNST, LHb, and VC/VS. Mean improvement in depression scores was significantly higher in the tractography cohort compared to the non-tractography cohort (tractography: 65.39±4.40%, non-tractography: 51.10±1.08%, p-value: 0.005). Improvements in depression symptoms was also compared within responders and non-responders to treatment. In both, patients who received tractography had a significantly higher mean improvement in depression scores (tractography-responders: 81.31±2.84%, non-tractography-responders: 74.14±1.44%, p-value: 0.031; tractography-non-responders: 33.54±3.59%, non-tractography-non-responders: 21.09±2.33%, p-value: 0.008). The higher percent mean improvements in tractography patients remained while controlling for the surgical targets.

Conclusion : We demonstrate that pre-operative tractography results in improved outcomes for depression management, independent of the surgical target. Given the patient-specific network structure of depression, absence of personalized neuromodulation may account for some of the response heterogeneity observed in clinical trials. Further research is needed to elucidate the mechanisms of action and optimal targets.