Deep Brain Stimulation Offers New Hope for Treatment-Resistant Depression

By Joao L. de Quevedo, MD, PhD, Director, Center for Interventional Psychiatry UTHealth Houston
September 8, 2025

image of brain

Major depressive disorder (MDD) remains one of the leading causes of disability worldwide, with nearly 200 million people affected. While many respond well to antidepressants, psychotherapy, or neuromodulation approaches like TMS and ECT, up to 40% of patients experience little to no relief even after multiple treatment attempts. For this group—patients with treatment-resistant depression (TRD)—clinicians and researchers continue to search for innovative solutions.

A newly published meta-analysis in the Journal of Neurosurgery highlights the growing role of deep brain stimulation (DBS) in addressing TRD. DBS, a therapy more commonly known for treating movement disorders such as Parkinson’s disease, involves implanting electrodes into specific brain regions to deliver targeted electrical impulses.

What This Study Found

The research team conducted a network meta-analysis of 22 clinical trials (15 sham-controlled), comparing different DBS targets for TRD. Their findings shed light on which brain circuits may hold the most promise:

  • Medial Forebrain Bundle (MFB):
    • Associated with the most significant reduction in depressive symptoms.
    • Achieved the highest responder rate (86%).
    • Likely effective because of its central role in dopamine pathways involved in motivation and reward.
  • Subcallosal Cingulate Gyrus (SCG) & Anterior Limb of the Internal Capsule (ALIC):
    • Both showed significant improvements compared to sham stimulation.
    • However, neither outperformed MFB stimulation.
  • Epidural Prefrontal Cortex (EPFC):
    • Associated with the highest remission rate (60%), though not statistically superior to other regions.

Overall, DBS was consistently more effective than sham stimulation, with MFB ranking as the top target across analyses.

Why This Matters

These findings point toward the MFB as a particularly promising target for future DBS interventions in depression. Unlike other brain areas, the MFB directly connects midbrain dopamine centers to the prefrontal cortex, making it a powerful hub for regulating mood and motivation.

Still, the authors caution that more research is needed. Very few trials directly compare one brain region to another, and many studies have small sample sizes. Head-to-head studies will be crucial to determine which patients benefit most from specific targets.

Looking Ahead

At UTHealth Houston Psychiatry, our Center for Interventional Psychiatry continues to explore advanced treatments for patients who have not found relief with traditional therapies. DBS represents a frontier in psychiatric neurosurgery, offering real hope to those living with the most difficult-to-treat forms of depression.

As this research evolves, patients may one day benefit from more personalized neuromodulation strategies—guided by brain circuitry, clinical features, and biological markers—to achieve lasting recovery.

Reference
Naik A, Chu T, Gupta R, et al. Deep brain stimulation for treatment-resistant major depressive disorder: a network meta-analysis of stimulation targets. J Neurosurg. Published online September 5, 2025. doi:10.3171/2025.4.JNS242393

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