Mood enhancement and Neural Network Modulation with Transcutaneous Vagus Nerve Stimulation (tVNS)​

Depression and the vagus nerve

Depression affects millions of people worldwide and constitutes a leading cause of disability. Although pharmacological interventions are available, many of them produce suboptimal outcomes due to high non-responsive rates or intolerable side effects.

It has been estimated that between 20 to 40 per cent of patients either failed to respond to conventional antidepressant therapies, or were forced to withdraw from treatment due to intolerable side effects [1]. As such, there is an urgent need to find alternative treatments.

Vagus Nerve Stimulation (VNS) has been shown to enhance mood and modulate certain neural networks and as a result is a promising intervention for this area. Many studies have shown clinical benefits of VNS in depressed patients, and the FDA has granted clearance for use in treatment-resistant individuals. However, conventional VNS requires surgery and the risk of complications has limited its wider adoption.

Non-invasive vagus nerve stimulation

Transcutaneous vagus nerve stimulation, or tVNS, is a new breakthrough treatment that stimulates the vagus nerve via a non-invasive route - through the skin of the ear. A recent study published by a collaborative research team drawn from Chinese and American universities had demonstrated the efficacy of tVNS in treating depression [2].

The research focused on the mood-enhancing effect of tVNS treatment alone in participants suffering from mild to moderate depression. A total of 49 participants were recruited into two cohorts: one received tVNS while the other received a sham treatment (identical device was used but the stimulation points were adjusted to a location with no vagus nerve distribution).

All patients were trained to apply the tVNS or the sham treatment, and subsequent therapies were self-administered at home. They were asked to use the device at least 5 days each week for 4 weeks, with two 30 minute sessions each day.

To assess the efficacy, the researchers evaluated the difference in depression rating before and after treatment in both groups. The measurement was carried out with four standardised tools to ensure the validity of the results. These were the Hamilton Depression Rating Scale, Hamilton Anxiety Rating Scale, Self-Rating Depression Scale and Self-Rating Anxiety Scale.

In addition, MRI brain scans were also obtained to show researchers a more in-depth look into the changes in brain functions and signaling with respect to tVNS treatments.

Clinical Outcomes

This research showed that tVNS significantly reduced the symptoms of depression when compared to the sham treatment. This could be attributed to its neuro-modulating effect of vital brain connections known as the default mode network (DMN) that regulates mood and emotion. Patients who received tVNS scored significantly lower on the Hamilton Depression Rating Scale compared to those who received the sham treatment.

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HAM-D, Hamilton Depression Rating Scale; HAM-A, Hamilton Anxiety Rating Scale; SAS, Self-Rating Anxiety Scale; SDS, Self-Rating Depression Scale. tVNS, transcutaneous vagus nerve stimulation; * indicates significant difference in mean score before and after treatment.

Brain scans also revealed the positive effects of tVNS on several key regions that have been linked with emotional regulation. The connectivity between the DMN and the right anterior insula and parahippocampus was reduced significantly, while the opposite effect occurred between the DMN and precuneus and orbital prefrontal cortex. The researchers believed such adjustments in connectivity between key brain regions could explain the improvement in depression score.

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Red colour regions showed decreased connectivity with DMN after treatment. Green colour regions showed changes in connectivity with DMN that corresponded with a lower Hamilton Depression Rating Scale.

While there are limitations such as trial design, the use of a tVNS device as described here will be very similar to the real world use. Further tVNS may confer greater benefits over a longer term as the current study only examined the effect over a 4-week period and responses in invasive VNS studies are typically seen over a longer period of time.

In summary, the study provides further evidence to support the use of tVNS in reducing depression severity and enhancing mood. As such, the technology provides new hope to millions of affected individuals of a life with better mental and emotional health.

References

1. Sackeim HA. The definition and meaning of treatment-resistant depression. J Clin Psychiatry 2001;62 Suppl 1:10–7.

2. Fang J, Rong P, Hong Y, et al. Transcutaneous Vagus Nerve Stimulation Modulates Default Mode Network in Major Depressive Disorder. Biol Psychiatry 2016;79:266–73. doi:10.1016/j.biopsych.2015.03.025

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