Invasive vagus nerve stimulation (VNS) is an adjunctive long-term treatment option for chronic and recurrent difficult-to-treat depression (DTD).

In this prospective observational open-label case series we report on the effects of invasive VNS on depression severity, medication load and the need of maintenance electroconvulsive therapy (ECT) and esketamine treatment after 12 months.

Patients were treated with invasive VNS according to clinical indication. All patients were included in the Restore-Life-Study. The assessment of depression severity (MADRS) and concomitant treatment was performed at baseline and in 3-months intervals postoperatively over a 12 months period.

Twelve patients were treated with adjunctive VNS due to unipolar (n=10) and bipolar (n=2) depression. The majority of patients were female (n=9). The mean age at baseline was 53.8 years (range 38-66). Patients were severely affected by a variety of depression symptoms which was reflected in high MADRS Scores (median 29, mean 28) at baseline. All patients received at least 2 or more psychotropic drugs at baseline. After 12 months of VNS a clear reduction of MADRS Scores (41 % on average) was seen (12-months MADRS Score median 17, mean 18). After 12 months, one patient each was discontinued from maintenance ECT and esketamine, respectively. The median of drug load was reduced from 4,56 to 4,06 after 12 months.

Invasive VNS is an effective treatment option in the long-term management of DTD to reduce the need of concomitant drug dose and maintenance treatment.

E Kavakbasi received speaker fees from Livanova. BT Baune received speaker and advisor fees from Livanova. The patients were included in the Restore-Life Study sponsored by LivaNova.

Vagus nerve stimulation produces therapeutic effects for the treatment of psychiatric disorders, heart failure, and others.

The aim of the current study was to evaluate the effects of the non-invasive vagus nerve stimulation on emotional burnout.

6 right-handed male volunteers aged 18-22 years participated in study. We used the combination of pleasant meditative classical music and a slow bi-polar wave (0.1-0.2 Hz) of electrical non-invasive transcutaneous auricular vagus nerve stimulation for 5 minutes. The set of 4 VNS was performed at intervals of 3 days. EEG was registered during the rest state (3 min, closed eyes condition). To measure the severity of emotional burnout in students, we used the 22-item Maslach Burnout Inventory (MBI).

VNS significantly improve the depersonalization and reduction of personal achievements (components of the emotional burnout). Changes in the psychoemotional state of the respondents were accompanied by the increase in the theta-Fz/alpha-Pz ratio, that reflects an enhancement of the activation level. A set of non-invasive stimulation of the auricular branch of the vagus nerve leads to an increase in the level of activation (the ratio of beta / alpha rhythms). The changes in the power of the alpha rhythm may relate to improving of mental process, creativity, creative thinking. An increase in alpha rhythm may reflect internally oriented attention in creative activities.

The preliminary data suggests that the novel mastoid stimulation device may have a prolonged stimulating effect on the brain processes while attenuating the burnout at the same time.

No significant relationships.

Depression is a leading cause of disability affecting over 300 million indivuals worldwide. About 1/3 of patients with depression fail to achive remission despite treatment with multiple antidepressants and are considered to have treatment-resistant depression (TRD). In view of such facts, vagus nerve stimulation (VNS) therapy was approved as an adjunctive long-term treatment for TRD.

The authors elaborate a narrative literature review about de effectiveness of VNS in treatment for TRD.

PubMed database searched using the terms “treatment-resistant depression”, “vagus nerve stimulation”

The pathophysiology of depression is complex and includes social environmental stress factors, genetic and biological processes, inflammation, and disturbances in monoamine neurotransmission. The overdrive of the HPA axis is most consistently seen in subjects with more severe depression, when the cortisol feedback inhibitory mechanisms are impaired, contributing to cytokine oversecretion. It has been shown that chronic exposure to elevated inflammatory cytokines can lead to depression. The vagus nerve represents the main component of the parasympathetic nervous system, which oversees a vast array of crucial bodily functions, including control of mood and imune response. VNS therapy has a demonstrated anti-inflammatory effect which might be a significant reason for its efficacy in patients who did not respond to antidepressants. Treatments thar target the vagus nerve increase the vagal tone and inhibit cytokine production and the stimulation of vagal aferente fibers in the gut influences monaminergic brain systems.

The mecanismos by which VNS may benefit patients nonresponsive to conventional antidepressants is unclear, with further research need to clarify this.

No significant relationships.

Vagus nerve stimulation (VNS) is a neuromodulation technique approved for Treatment-Resistant Depression (TRD). Evidence regarding its long-term efficacy and safety is still scarce.

To descriptively report a case series of 3 patients undergoing adjunctive VNS for TRD with an over 10-year follow-up.

We investigated outcomes of clinical interest in patients with ongoing VNS for at least 10 years after the device implantation. They had participated in a larger single-arm interventional study conducted at the University Hospital of Padua. They were diagnosed with chronic unipolar (1), recurrent unipolar (1), and bipolar (1) TRD.

Our 3 cases had an average 14-year history of psychiatric disease before surgery. Afterward, all subjects achieved clinical remission within two years. 2 patients experienced relapses within the first 4 years of treatment (respectively, 1 and 2 episodes). The other case showed a recurrent trend of brief relapses every two years. Only 1 individual needed to be admitted to the psychiatric unit once. None of them committed suicidal attempts. Prescription of antidepressants remained almost unchanged after the first two years. 2 individuals improved and 1 maintained their working position. Common adverse events were voice alteration (3/3), neck pain (2/3), and cough (2/3).

Very few cases of 10-year VNS for TRD have been reported so far. For our subjects, VNS was most likely to have a major impact on the clinical course of the disease. This treatment can be a safe and effective adjunctive intervention in a subgroup of patients with TRD.

To determine the efficacy of vagus nerve stimulation (VNS) for treatment of depression.

We conducted a systematic review and meta-analysis of analytical studies. Efficacy was evaluated according to severity of illness and percentage of responders.

We identified 687 references. Of these, 14 met the selection criteria and were included in the review. The meta-analysis of efficacy for uncontrolled studies showed a significant reduction in scores at the Hamilton Depression Rating Scale endpoint, and the percentage of responders was 31.8% ([23.2% to 41.8%], P<0.001). However, the randomised control trial which covered a sample of 235 patients with depression, reported no statistically significant differences between the active intervention and placebo groups (OR=1.61 [95%CI 0.72 to 3.62]; P = 0.25). To study the cause of this heterogeneity, a meta-regression was performed. The adjusted coefficient of determination (R2Adj) was 0.84, which implies that an 84% variation in effect size across the studies was explained by baseline severity of depression (P<0.0001).

Currently, insufficient data are available to describe VNS as effective in the treatment of depression. In addition, it cannot be ruled out that the positive results observed in the uncontrolled studies might have been mainly due to a placebo effect.

Transcutaneous vagus nerve stimulation (tVNS) is a promising therapeutic option for major depressive disorder (MDD) in adults. Alternative third-line treatments for MDD in adolescents are scarce. Here we aimed to assess the effects of acute tVNS on emotion recognition in adolescents with MDD.

Adolescents (14–17 years) with MDD (n = 33) and non-depressed controls (n = 30) received tVNS or sham-stimulation in a cross-sectional, case–control, within-subject cross-randomized controlled trial, while performing different tasks assessing emotion recognition. Correct responses, response times, and errors of omission and commission on three different computerized emotion recognition tasks were assessed as main outcomes. Simultaneous recordings of electrocardiography and electro dermal activity, as well as sampling of saliva for the determination of α-amylase, were used to quantify the effects on autonomic nervous system function.

tVNS had no effect on the recognition of gradually or static expressed emotions but altered response inhibition on the emotional Go/NoGo-task. Specifically, tVNS increased the likelihood of omitting a response toward sad target-stimuli in adolescents with MDD, while decreasing errors (independent of the target emotion) in controls. Effects of acute tVNS on autonomic nervous system function were found in non-depressed controls only.

Acute tVNS alters the recognition of briefly presented facial expressions of negative valence in adolescents with MDD while generally increasing emotion recognition in controls. tVNS seems to specifically alter early visual processing of stimuli of negative emotional valence in MDD. These findings suggest a potential therapeutic benefit of tVNS in adolescent MDD that requires further evaluation within clinical trials.