Summary: For approximately 30% of people living with depression, standard medications and therapy simply do not work—a condition known as treatment-resistant depression. Researchers are now investigating Deep Brain Stimulation (DBS) as a potential lifeline for these patients.
Already FDA-approved for Parkinson’s and other movement disorders, DBS acts like a “pacemaker for the brain,” using implanted electrodes to deliver precise electrical pulses. While still in the clinical trial phase for mental health (including the national TRANSCEND trial), early data suggests that by targeting the brain’s “white matter” communication highways, DBS can help “unstick” a brain trapped in a chronic depressive state.
Key Facts
- The “Unstucking” Goal: DBS for depression is not a “happy switch.” Instead, it aims to reduce biological barriers, allowing the brain to move out of a stagnant, depressed state so patients can once again engage in meaningful life activities.
- White Matter vs. Gray Matter: Unlike Parkinson’s treatment (which targets gray matter), depression DBS targets white matter—the brain’s communication highways. Because of this, the effects are more gradual, often taking weeks or months to unfold.
- The TRANSCEND Trial: UTSW is a site for this gold-standard, double-blind study. To ensure total objectivity, neither the patients nor the doctors know who is receiving active stimulation during the initial study phase.
- Eligibility: Candidates typically include adults who have not responded to four or more treatments and have a history of severe, long-term depressive episodes.
Source: UT Southwestern
For many people living with depression, medications, psychotherapy, and other treatments can be life-changing.
But for approximately 30% of patients, depression remains severe and persistent despite trying multiple well-established therapies. This is known as treatment-resistant depression, also known as difficult-to-treat depression.
Sometimes, standard therapies do not work for depression symptoms for biological reasons. But for other patients, it’s the demands of treatment or treatment-related side effects – not the treatment itself – that preclude continued treatment with a particular therapy.
For these patients, finding successful symptom management requires a team of experts who understand the complexities and nuances of depression care. UT Southwestern combines the expertise of specialists ranging from psychiatrists to neurosurgeons to find effective, sustainable solutions for patients with treatment-resistant depression.
One of the latest areas of research here and at other centers nationally has been deep brain stimulation (DBS), which has traditionally been used to treat conditions such as Parkinson’s disease, essential tremor, dystonia, and other movement disorders.
DBS is not yet approved by the U.S. Food and Drug Administration for depression and is currently available only through clinical trials for this condition. Yet early experiences in select patients, including at UTSW, suggest this therapy may offer hope for people who have not found relief with other treatments.
How is ‘treatment-resistant depression’ defined?
Generally speaking, “treatment-resistant depression” means a person’s symptoms have not improved after adequate treatment with at least two to three standard medications. But simplifying this definition to a specific number of treatments overlooks the nuances of living with depression. Many factors can contribute to a patient’s emotional and physical state including:
- Sleep, diet, and hydration
- Taking medications as prescribed
- Work, family, or social responsibilities that may contribute to symptoms
- Access to therapy
- Other health problems a patient is dealing with
For patients who struggle with these factors, a drug may help – but it must be used on time, as prescribed, and consistently. Furthermore, there are some patients for whom medications are ineffective despite adequate adherence, dosage, and duration of treatment.
For these patients – and for those whose depression is truly resistant to treatment – there are other options. Some of these include:
- Ketamine or esketamine medication: Ketamine is an anesthetic, dissociative drug that can create a sense of detachment. Research suggests it can provide quick benefits for people with serious depression and suicidal thoughts. Ketamine is given intravenously (IV) under close supervision. Esketamine is a special formulation of ketamine that can be administered via a nasal spray that can also be used to treat depression.
- Transcranial magnetic stimulation (TMS): TMS is a procedure that uses magnets precisely placed on the head to modulate nerve cells in the brain that are involved in mood regulation and depression. Patients typically get 30- to 45-minute treatments five times a week, which can provide significant improvement in depression symptoms.
- Electroconvulsive therapy (ECT): ECT is a safe, effective outpatient procedure that delivers electrical current to the brain via pads placed on the head. A brief, controlled seizure is induced under anesthesia to relieve depression. Patients typically get ECT two to three times a week for several weeks under close monitoring. At UTSW, we perform more ECT procedures than any other center in Texas and have been part of several groundbreaking ECT clinical trials.
How does DBS work?
Deep brain stimulation is like a pacemaker for the brain. It provides a small amount of electricity to correct abnormal brain activity. The two main parts of a DBS system are the thin wires that go into the brain and a battery placed under the skin below the collarbone.
There are two main types of batteries: rechargeable and nonrechargeable. Rechargeable batteries are smaller, designed to last many years, and must be recharged at home using a wireless charger. Nonrechargeable batteries typically last only a few years and can be replaced with a short outpatient (same-day) surgery.
After the device is activated, patients do not feel the electrical pulses. DBS patients can participate in their normal activities, including swimming or soaking in a hot tub, after the surgical wounds are healed. Similar to a pacemaker, the device can be deactivated should a patient choose to discontinue the treatment. The device can also be removed if necessary and the effects of stimulation are reversible.
DBS has been proved to be safe and highly effective for movement disorders. It can dramatically reduce tremors, stiffness, and slowness of movement – usually immediately after the device is turned on.
However, early research studies have shown that the recovery process is more gradual for serious depression due to differences in targeted areas of the brain and the disease being treated.
How is DBS used to treat depression?
In movement disorders, we target and stimulate gray matter, areas of the brain that generate brain activity. For depression, the target is white matter – the brain’s communication highway that connects various regions involved in mood, motivation, and emotional regulation.
Because of this difference, DBS for depression uses higher levels of stimulation and works more gradually. Mood does not change overnight. Improvement typically unfolds over weeks to months.
DBS for depression is not a “happy switch,” and it does not force a person to feel joy. The goal is to help the brain get “unstuck” and to reduce the biological barriers that keep a patient trapped in a depressed state.
Through DBS, some patients who do not get adequate relief from standard depression treatments may be able to once again enjoy meaningful activities and relationships.
Some people improve with treatments such as ECT but their depression symptoms can return over time. These patients may be the best candidates for DBS because their brain has demonstrated an ability to change.
How can I get access to DBS for depression?
DBS for depression is currently available only through research studies. UT Southwestern is proud to offer our own study of DBS for depression as well as serving as a center recruiting patients for the TRANSCEND trial, a large, randomized, double-blind, placebo-controlled study – the gold-standard for clinical research.
Earlier clinical trials of DBS for depression have sometimes been described as “failed.” Those studies were short, and both the treatment and placebo groups reported symptom improvement. Though the data did not definitively determine the specific benefits of DBS, anecdotal accounts report that some patients in those trials had symptom relapse after the battery was depleted.
Furthermore, many patients continued to improve after multiple years of stimulation. These findings suggest the devices provided benefit, and this work helped inform both our institutional clinical trial and the TRANSCEND trial design.
Both trials will follow patients for at least a year, allowing researchers to see whether benefits emerge gradually and persist. For the TRANSCEND study, all participants will get a nonrechargeable battery to keep the study double-blinded, meaning neither the patient nor the care team knows who is receiving DBS treatment. If appropriate, the battery can be exchanged for a rechargeable one in an outpatient procedure after the study concludes.
Who might be eligible for the clinical trials of DBS for depression?
Some of the eligibiity criteria for adults interested in joining these clinical trials include:
- Diagnosis of major depressive disorder.
- Stable medication and treatment regimen for at least four weeks before the first visit.
- Living within a major depressive episode for longer than three months or at least three depressive episodes in their lifetime.
- Inadequate response to four or more depression treatments.
- Not being currently pregnant.
- Not being at acute risk of suicide.
- Not having a current or lifetime history of psychosis.
Patients will continue to take their normal medications and participate in psychotherapy if that already was part of their treatment. The goal is to keep all other treatments as stable as possible to determine the specific effects of DBS on a person’s depression.
Because DBS requires a procedure, careful and thorough evaluation is critical. Patients are assessed by experienced interventional psychiatrists who are familiar with the full range of depression treatments. Multiple psychiatrists must agree that DBS is an appropriate option before a patient can move forward in the trial.
A bright future for depression treatment
If the TRANSCEND trial shows clear benefit, the results would support potential FDA approval of DBS use for treatment-resistant depression. The approval process takes time; optimistically, this therapy could become more widely available within five years.
There is not yet a cure for depression, and most people benefit from a combination of treatments. The goal is to help people move out of depressive episodes and reduce the impact of the disease on their lives.
If you or a loved one struggle with treatment-resistant depression, talk with your mental health care provider about advanced treatment options. For some patients, joining a clinical trial or trying an advanced treatment can offer a chance to engage with life again in a more fulfilling way.
Key Questions Answered:
A: No. Researchers emphasize that DBS isn’t a “joy button.” Its purpose is to clear the biological “fog” and barriers that keep a person stuck. Patients report that it simply allows them to feel like themselves again, making it possible to experience normal emotions—both good and bad—and engage with the world.
A: While both use electricity, they are very different. ECT involves a brief, controlled seizure under anesthesia a few times a week. DBS is a continuous form of stimulation provided by an implanted device. Interestingly, patients who responded well to ECT in the past but saw their symptoms return are often the best candidates for DBS.
A: The effects are reversible. Like a heart pacemaker, the device can be turned off or even surgically removed if a patient chooses to discontinue treatment. The stimulation doesn’t damage brain tissue; it simply “modulates” the electrical signals traveling through it.
Editorial Notes:
- This article was edited by a Neuroscience News editor.
- Journal paper reviewed in full.
- Additional context added by our staff.
About this neurotech and depression research news
Author: Frederick Hitti
Source: UT Southwestern
Contact: Frederick Hitti – UT Southwestern
Image: The image is credited to Neuroscience News
