Bed nucleus of the stria terminalis-nucleus accumbens stimulation for depression: A randomized, double-blind, crossover trial

Clinical Snapshot

Key Findings

• P Value: p < 0.001

• Effect Size: 10.1 point reduction in HAMD-17 (clinically significant)

• Primary Outcome: Mean decrease in HAMD-17 scores of 10.1 points

• Nnt Or Sensitivity: 50% response rate (NNT = 2 for response)

• Confidence Interval: Not reported

Clinical Application

Limited to specialized neurosurgical centers with DBS expertise and multidisciplinary psychiatric teams Would require TGA approval for this indication; limited to major tertiary centers; not currently PBS-funded; would need RANZCP and neurosurgical society guidelines Highly selected patients with severe, treatment-resistant depression who have failed multiple conventional therapies

Abstract

Although deep brain stimulation (DBS) shows potential in treatment-resistant depression (TRD), the efficacy remains controversial. To assess the efficacy of DBS of the bed nucleus of the stria terminalis (BNST) and nucleus accumbens (NAc) for TRD, we conduct a randomized, double-blind, crossover trial after an open-label optimization stage. Stimulation leads to a mean decrease in the Hamilton Depression Scale-17 (HAMD) scores of 10.1 points (p < 0.001) with a 50% response rate at the end of the open-label stage. Anxiety, quality of life, and disability are also improved. The HAMD scores are significantly lower in patients during active DBS than during sham DBS (p < 0.001). Serious adverse events include suicide (1 patient) and seizure (1 patients). With individual stimulation analysis, we identify optimal stimulation sites, fiber tracts, and functional networks (false discovery rate [FDR] p < 0.05). This study demonstrates the efficacy and safety of BNST-NAc DBS for TRD and reveals optimal brain targets for stimulation. This study was registered at ClinicalTrials.gov (NCT04530942).

References

1. 1.Lai, Y., Zhang, Y., Wang, Y., Wang, L., Dai, L., Ye, K., Lv, X., Wang, F., Zhang, J., Zhao, Y., Hu, K., Huang, P., Zhang, X., Qiu, X., Pan, Y., Liu, W., Liu, Q., Zhang, C., Fang, Y., Ye, Z., Yuan, T. F., Li, D., Li, N., Lozano, A. M., Voon, V., Zhan, S., & Sun, B. (2026). Bed nucleus of the stria terminalis-nucleus accumbens stimulation for depression: A randomized, double-blind, crossover trial. Cell Reports Medicine, 15(4), 102711. https://doi.org/10.1016/j.xcrm.2026.102711