Are There Any New Treatments for Depression?

Summary: Yes, there are several new treatments for depression currently undergoing clinical trials for safety and effectiveness.

Key Points:

• New treatments for depression that get the most publicity include psychedelic and dissociative medications such as psilocybin, ketamine, Spravato®, MDMA, and LSD.
• New treatments for depression that are equally promising but get far less publicity include brain stimulation therapies such as transcranial magnetic stimulation (TMS) and vagus nerve stimulation (VNS).
• A new study reviews the effectiveness of vagus nerve stimulation on patients with treatment resistant depression (TRD).

A New Approach to Brain Stimulation

When we hear electrical stimulation and mental health in the same sentence, most of us conjure up negative associations with traditional, old-school electroshock therapy. Those therapies from the early days of electrical stimulation treatment for mental health, which we now call electroconvulsive therapy (ECT), involved high, unsafe levels of electrical current delivered without anesthesia or medication. More often than not, they caused significant pain, injuries like broken bones, and additional side effects including serious fear of treatment and distrust of doctors and/or providers who recommended or approved the treatment.

Those days are gone. In 2026, there are several safe and effective variations of electrical stimulation therapy available for a variety of different mental health disorders, which are now classified as brain stimulation therapies, or BSTs.

The National Institute of Mental Health (NIMH) reports three types of safe and effective BSTs currently approved by the Food and Drug Administration (FDA):

• Electroconvulsive therapy (ECT)
• Transcranial magnetic stimulation (TMS)
• Vagus nerve stimulation (VNS)

In addition, there are two types of BST, magnetic seizure therapy (MST) and deep brain stimulation (DBS), which are in the final stages of clinical trials, and may be approved soon. These therapies use electricity or electromagnetic pulses to either induce a momentary seizure or stimulate key brain areas associated with emotion and cognition.

In this article, we’ll share the results of a new study on VNS conducted by scientists at Washington University School of Medicine in St. Louis, MO, called “Durability of the Benefit of Vagus Nerve Stimulation in Markedly Treatment-Resistant Major Depression: A RECOVER Trial Report.” The researchers identified this experimental goal:

“Characterize depressive symptoms, function, and quality of life (QoL) over 24 months of adjunctive vagus nerve stimulation (VNS) in participants with markedly treatment-resistant depression.”

Let’s take a closer look at why scientists are exploring VNS for markedly TRD.

New Treatments for Depression: Vagus Nerve Stimulation (VNS)

We used a term that’s not very common, above: markedly treatment resistant depression. Treatment resistant depression (TRD) is defined as major depressive disorder (MDD) that fails to respond to at least two attempts at treatment with standard medication and protocols. Markedly treatment resistant depression, on the other hand, is defined as major depressive disorder (MDD) that fails to respond to (4) or more attempts at depression treatment under standard protocols with psychotherapy and antidepressant medication.

In an interview published online, the lead author of the study, Dr. Charles Conway, observes:

“There is a dire need to find effective treatments for these patients, who often have no other options. With this kind of chronic, disabling illness, even a partial response to treatment is life-altering, and with vagus nerve stimulation we’re seeing that benefit is lasting.”

That’s important to understand: TRD is a serious condition and people with severe TRD, i.e. markedly TRD, experience serious disruption, disturbance, and functional impairment as a result of the intensity, frequency and duration of the symptoms.

Before we dive into the study, we’ll also offer this explanation of what the vagus nerve is and does:

“The vagus nerve is a part of the parasympathetic and sensory nervous systems that serves as a direct connection between the brain and the enteric nervous system. It is a mixed nerve containing both afferent and efferent fibers and is often referred to as the “sixth sense.” The vagus nerve plays a crucial role in interoceptive awareness and has an immunomodulatory function.”

Its association with the parasympathetic nervous system and functional role interoceptive awareness, i.e. our ability to interpret and understand our internal sensations, led scientists to explore a possible role for vagus nerve stimulation in mental health treatment. Initial research shows positive results on patients with markedly TRD after treatment with a cervically implanted VNS device.

Now let’s take a closer look at the study itself.

Testing Vagus Nerve Stimulation for Depression Can It Help People With TRD?

The research team recruited 249 patients with clinically defined markedly TRD and assigned them to an active VNS protocol as an adjuvant to typical psychotherapy. Patients received a surgically implanted VNS device that delivers electrical impulses at predetermined times, durations, and intensities. In most cases, the pulses occur in short, repetitive cycle throughout the day. However, physicians and technicians have the ability to alter, adjust, and fine tune the device to achieve optimal treatment effect.

To measure the impact on depression and quality of life, the researchers administered the following assessments at baseline, then at 12 months, 18 months, and 24 months after implant and initiation of vagus nerve stimulation:

• Montgomery-Asberg Depression Rating Scale (MADRS), measures depression.
• Quick Inventory of Depressive Symptomatology–Clinician (QIDS-C), measures depression.
• Quick Inventory of Depressive Symptomatology–Self-Report (QIDS-SR), measures depression.
• Clinical Global Impression–Severity (CGI-S), measures general psychiatric condition.
• Clinical Global Impression–Improvement (CGI-I), measures general psychiatric condition.

In addition, the researchers developed what they call a tripartite composite score, which is a combination of the three depression metrics and the two CGI metrics, and created this three-tiered scale to determine the general impact of VNS:

1. Meaningful benefit (MB): 30%-50% reduction in scores on selected metric or composite
2. ≥Meaningful Benefit (≥MB): At least 30% reduction in scores on selected metric or composite
3. Substantial Benefit (SB): ≥50% reduction in scores on selected metric or composite
4. No Benefit (NB): fail to meet criteria for MB, ≥MB, or SB.

Now let’s look at what they found.

VNS: Can It Help People With TRD?

Here are the results of the study. We included the core findings on effectiveness and duration of effectiveness. For a detailed examination of various additional outcomes, please refer to the source study via the link above.

Outcomes: Depression and Overall Psychiatric Status at 12, 18, and 14 Months Post Treatment

Depression (MADRS):

• ≥MB:
  • 12: 43.6%
  • 18: 49.2%
  • 24: 53.6%
• SB:
  • 12: 28.7%
  • 18: 32.6%
  • 24: 34.3%
• MB:
  • 12: 14.9%
  • 18: 16.6%
  • 24: 19.3%
• Remission:
  • 12: 15.5%
  • 18: 18.2%
  • 24: 21.5%
• NB:
  • 12: 56.4%
  • 18: 50.8%
  • 24: 46.4%

Depressive Symptoms, Clinician Report (QIDS-C):

• ≥MB:
  • 12: 55.8%
  • 18: 58.6%
  • 24: 62.4%
• SB:
  • 12: 33.7%
  • 18: 37.6%
  • 24: 40.9%
• MB:
  • 12: 22.1%
  • 18: 21.0%
  • 24: 21.5%
• Remission
  • 12: 19.3%
  • 18: 23.2%
  • 24: 24.3%
• NB:
  • 12: 44.2%
  • 18: 41.4%
  • 24: 37.6%

Depression, Self-Report (QIDS-SR):

• ≥MB:
  • 12: 61.3%
  • 18: 56.9%
  • 24: 59.1%
• SB:
  • 12: 38.1%
  • 18: 39.2%
  • 24: 41.4%
• MB
  • 12: 23.2%
  • 18: 17.7%
  • 24: 17.7%
• Remission
  • 12: 24.3%
  • 18: 21.5%
  • 24: 23.8%
• NB:
  • 12: 38.7%
  • 18: 43.1%
  • 24: 40.9%

Overall Mental Health Status (CGI-I):

• ≥MB:
  • 12: 68.6%
  • 18: 80.5%
  • 24: 77.3%
• SB:
  • 12: 41.1%
  • 18: 48.6%
  • 24: 51.9%
• MB:
  • 12: 27.6%
  • 18: 31.9%
  • 24: 25.4%
• Remission:
  • 12: 17.3%
  • 18: 17.23%
  • 24: 21.6%
• NB:
  • 12: 31.4%
  • 18: 19.5%
  • 24: 22.7%

Combined Depression/Quality of Life:

• ≥MB:
  • 12: 80.0%
  • 18: 83.6%
  • 24: 82.4%
• SB:
  • 12: 60.6%
  • 18: 67.3%
  • 24: 66.1%
• MB:
  • 12: 19.4%
  • 18: 16.4%
  • 24: 16.4%
• NB:
  • 12: 20.0%
  • 18: 16.4%
  • 24: 17.6%

Those outcomes are surprising and far exceed practical expectations for depression treatment and treatment for TRD in particular. In the interview we reference above, Dr. Coway offers this assessment of these experimental outcomes:

“We were shocked that one in five patients was effectively without depressive symptoms at the end of two years. Seeing results like that for this complicated illness makes me optimistic about the future of this treatment. These results are highly atypical, as most studies of markedly treatment-resistant depression have very poor sustainability of benefit, certainly not at two years. We’re seeing people getting better and staying better.”

We’ll discuss these results in further detail below.

New Treatment for Depression May Change Prognosis for People With Treatment Resistant Depression

As we mention above, this study contains promising news for people with TRD and markedly TRD. Many people with TRD give up hope that any type of treatment can help them in any way at all. To meet criteria for TRD, a patient must have an unsatisfactory response to two (2) treatment attempts, and for markedly TRD, that number increase to four (4).

For some patients, that could mean 1-2 years of treatment attempts, followed by disappointing results. If the results of this study are repeatable and consistent, then this could bring hope to patients with markedly TRD who may have lost hope in the process.

Here are additional outcomes highlighted by the research team:

• Among the 80% of patients who experienced clinically meaningful benefit (MB) on the tripartite composite score after a year of treatment, all reported the same level of improvement/benefit at 24 months post-implant.
• Meaningful benefit (≥MB) persisted for most patients at 18 at 24 months post-implant.
• A significant percentage of patients with no meaningful benefit at 12 months showed meaningful benefit.
• Two-thirds of patients with meaningful benefit (≥MB) at 12 months improved to MB by 24 months.

That’s more promising news for patients with TRD. When we learn more about the follow up studies on VNS, we’ll report them here. In the meantime, patients with TRD can find hope that new and effective treatments – like VNS – may become more readily available sooner, rather than later.