Could vagus nerve stimulation offer progress on treatment resistant depression?

Almost a third of people with major depressive disorder find that regular treatments, including anti-depressant drugs, or even electroconvulsive therapy, don't help. Now, a new year-long trial of a treatment that involves electrically stimulating the vagus nerve has found promising results for people suffering with exactly this type of this 'treatment-resistant' depression (TRD).

The double-blind, sham-controlled study, reported in Brain Stimulation, was led by Charles Conway at Washington University, US. It involved 493 adults diagnosed with severe TRD, who had not responded to at least four antidepressant treatments during their current depressive episode. On average, though, each patient had been sick with depression for more than half of their lives and already tried 13 treatments previously, without seeing any relief of their symptoms, commented Conway, in a statement. These patients, who were, in the researchers' words "chronically depressed and markedly treatment resistant" were recruited from 84 different sites across the US.

All were implanted with a device capable of stimulating the left cervical vagus nerve, which links the brain with various internal organs, including the heart and the gut. Other work has found that vagal stimulation can improve mood, and can even help people with treatment resistant depression. However, the US health insurance programme Medicare has considered the evidence on this to be insufficient, meaning that it couldn't be claimed for on insurance, and leading to calls for further work — hence this study.

After the devices were implanted, only about half (249) of the patients had their devices turned on. Neither they nor the other group were told whether they were receiving an active or a sham treatment. They all continued to follow their existing anti-depressant drug regimens, if any.

The team then followed these patients over the next 12 months. On their main outcome measure — the percentage of time that the participants experienced at least a 50% reduction in the severity of their depression — they found no difference between the active and the sham groups.

However, there were still some benefits to the therapy. Those who'd received the active treatment reported spending more time with lower levels of depressive symptoms (about 25% of the time for the treatment group, compared with about 20% of the time for the sham group). They also reported improvements in their daily lives and their ability to function.

Given the resistance of their depression to other treatments, this was striking, Conway said. 
"You have a population of people who have been failed by a ridiculously high number of treatments… and they're not just saying, 'Yeah, I feel a little bit better.' They're saying they are seeing meaningful improvements in their ability to function and live their lives.'

Most of the benefits became apparent during the last three months of the study, the team noted. This fits with findings from earlier studies that the benefits of vagal nerve stimulation can take time to appear.

Overall, the stimulation treatment was well tolerated, the most common side effects being dysphonia (voice alterations) and dyspnea (a sensation of running out of air) both of which have previously been observed in people receiving vagal nerve stimulation.

Though the team's paper reports on results to twelve months, at the end of the study period, those with the active devices continued to receive the vagal stimulation and the sham group had their devices turned on. The team plans to continue to follow all of the patients over four years, to explore the extent to which they ultimately benefit — and the impacts of the treatment over time.

Read the paper in full:
Conway, C. R. et al. (2024) Vagus nerve stimulation in treatment-resistant depression: A one-year, randomized, sham-controlled trial. Brain Stimulation, 0(0). https://doi.org/10.1016/j.brs.2024.12.1191

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