Revisiting Deep Brain Stimulation for Depression: Hope in the Subcallosal Cingulate

By Joao L. de Quevedo, MD, PhD, Director, Center for Interventional Psychiatry UTHealth Houston
September 2, 2025

image of electricity

Treatment-resistant depression (TRD) remains one of the most urgent challenges in psychiatry. Despite multiple advances—from new antidepressants to electroconvulsive therapy (ECT) and transcranial magnetic stimulation (TMS)—up to a third of patients continue to experience chronic, debilitating symptoms. For these individuals, sustained recovery has long felt out of reach.

A recently published pooled analysis in Brain Stimulation revisits one of the most promising but controversial approaches in the field: deep brain stimulation (DBS) targeting the subcallosal cingulate (SCC).

Why the Subcallosal Cingulate?

The SCC has been a focal point of depression research since early studies demonstrated its role in regulating mood circuits. DBS delivers continuous, adjustable electrical stimulation to this region, aiming to rebalance dysfunctional brain networks. While initial large-scale trials, such as the BROADEN study, struggled to show short-term benefits, long-term follow-ups suggested a different story: patients experienced gradual, durable improvements that extended over years.

The New Analysis

This new report combines data from five major SCC DBS studies across the U.S., Canada, and Europe, totaling 172 patients who were implanted with the same DBS system. Most participants had lived with depression for nearly a decade, many after exhausting pharmacological, psychotherapeutic, and neuromodulation options, including ECT.

Key findings included:

  • Sustained Symptom Reduction: Depressive severity scores (MADRS and HDRS-17) dropped by 43% after one year and 53% after two years.
  • Meaningful Response Rates: At 24 months, 55% of patients achieved clinical response, with nearly 40% reaching remission.
  • Durability: Improvements persisted throughout long-term follow-up, up to five years in some cohorts.
  • Safety Profile: Adverse events were generally consistent with other DBS uses (e.g., for Parkinson’s disease). Suicide and suicide attempt rates were comparable to those seen in TRD patients treated with ECT or vagus nerve stimulation, underscoring the high baseline risk in this population rather than device-related harm.

Why This Matters

These results highlight an essential truth: DBS may not work instantly—but for some, it provides steady and lasting relief where every other option has failed. Notably, the study also shows that outcomes improve with refined targeting strategies, particularly tractography-based approaches that map individual brain connectivity for more precise electrode placement.

As psychiatric neuromodulation evolves, DBS could become an integral part of TRD treatment, particularly for the most severe and chronic cases. However, further randomized controlled trials will be essential before widespread adoption.

Looking Ahead

The road from experimental therapy to standard care is a long one. Still, this new analysis offers renewed optimism for patients, families, and clinicians confronting TRD. By harnessing the brain’s circuitry with surgical precision, SCC DBS has the potential to transform lives where hope once seemed lost.

Reference

Himes LM, Mayberg HS, Husain MM, et al. Revisiting subcallosal cingulate deep brain stimulation for depression: Long-term safety and effectiveness outcomes from a pooled analysis of 172 implanted patients. Brain Stimulation. 2025;18:1632–1640. doi:10.1016/j.brs.2025.08.017

Contact

Request for Second Opinion Form – https://Go.uth.edu/CIPIntake.

Phone – (713) 486-2621

Fax – (713) 500-2728

E-mail – [email protected]