J Neurosurg. 2025 Sep 5:1-10. doi: 10.3171/2025.4.JNS242393. Online ahead of print.
ABSTRACT
OBJECTIVE: Major depressive disorder is a significant cause of disability, impacting an estimated 193 million individuals worldwide. Forty percent are estimated to have little to no response to standard pharmacological therapies. Deep brain stimulation (DBS) has emerged as a favorable neuromodulation therapy for treatment-resistant depression, but it remains unclear which brain targets are optimal.
METHODS: The authors performed a systematic literature review and meta-analysis of articles published through January 2022 to examine the efficacy of DBS targets in reducing depressive symptoms in patients with treatment-resistant depression. The primary outcome was the reduction in depression severity measured by the Montgomery-Asberg Depression Rating Scale and Hamilton Rating Scale for Depression. Secondary outcomes were responder and remission rates.
RESULTS: The authors analyzed 22 trials, 15 of which were sham-controlled studies. This network meta-analysis identified that stimulation of the medial forebrain bundle (MFB) was associated with the greatest reduction in depressive symptoms, compared with stimulation of the subcallosal cingulate gyrus (SCG) and ventral capsule/ventral striatum (VC/VS). Stimulation of the MFB also exhibited a higher responder rate (86%) than stimulation of the SCG or anterior limb of the internal capsule. Stimulation of the rostral extension of the prefrontal cortex was associated with the highest remission rate (60%), but this was not statistically significant compared with stimulation of other brain regions.
CONCLUSIONS: The MFB shows promise as a DBS target for treatment-resistant depression, possibly a result of its involvement in the mesocortical and mesolimbic pathways mediating depression. However, additional trials directly comparing stimulation of different brain regions are necessary to establish MFB as the optimal neurostimulation target.
PMID:40911913 | DOI:10.3171/2025.4.JNS242393
