Vagus nerve stimulation (VNS) for treatment-resistant depression.

Bruno Kägi, MD, Zurich, reported on his experience with VNS and explained how it can be combined with other psychiatric treatments in cases of severe or treatment-resistant depression.

The vagus nerve consists of 80% afferent fibers that terminate predominantly in the nucleus tractus solitarius (NTS), which is connected to the amygdala and the limbic system. Stimulation of the vagus nerve affects neurotransmitters such as gamma-aminobutyric acid (GABA), serotonin, and norepinephrine [1]. There are others, but they play a minor role.

The role of the vagus nerve has been studied for over one hundred years. In 1988, the company was founded by Dr. Kiffin Penry first treated a patient with refractory epilepsy with VNS. The procedure was first approved by the FDA in 1997. Since then, it has been used worldwide in the treatment of epilepsy when conventional drugs do not work. Since the beginning of this century it has also been used in Switzerland for depression.

Concept of treatment-resistant depression

“Treatment-resistant depression” (TRD) can be said to occur when there is an inadequate response to usual therapy in the context of the relevant guidelines, Kägi elaborated. “Response” is the opposite of “resistance”. In research, “response” means a greater than 50% reduction in symptoms from “baseline” as measured by standardized rating scales [2,3]. Nearly half of the remitted patients still have symptoms – a full remission is rather rare anyway. At least 35% of patients are non-responsive for depression despite forced therapy with more than four conventional treatments. The suicide rate in this group is twice as high as in the non-therapy resistant depression group [4].

Mode of action of the VNS

The VNS alters pathways between the NTS, amygdala, and limbic system over an extended period of time (approximately three quarters of a year). β-adrenergic receptors are activated. It also modulates the activity of limbic, paralimbic, and cortical structures. Regional blood flow (rCBF) in the dorsolateral and prefrontal cortex is altered [6–8].

This increases the concentration of monoamines and produces an effect similar to that of SSRIs. Dr. Kägi went on to say that almost all patients reported augmenting existing therapy with VNS.

The efficacy of VNS showed up to 60% reduction in depressive symptoms, although some of the studies had low case numbers, Dr. Kägi said [9]. Efficacy can also be achieved for anxiety or obsessive-compulsive disorders over a period of more than half a year [10,11]. A metastudy of 14 uncontrolled studies showed a “response” of 31.8% [12]. In a study of outcome in TRD, treatment as usual (TAU) together with VNS achieved better results than TAU alone in a five-year follow-up, with a cumulative response rate of 67.6% compared with 40.9% [13].

Compatibility

From his practice, Dr. Kägi was able to report that VNS is generally well tolerated. Hoarseness, coughing or shortness of breath during stimulation, and neck pain were among the side effects that could be easily controlled by readjusting the stimulation settings (frequency, current intensity, pauses). In the case of swallowing difficulties, acid regurgitation and vomiting, it may be necessary to take countermeasures with medication. Rarely, tachycardia is noted, which may need to be treated with beta-blockers. Wound infection is also rare, he said. The dosages must be adapted to the individual patient in a finding process. In addition to adjusting the stimulation itself, additional psychotropic drugs (SSRI, SNRI) can support the effect. Contraindications exist in cases of acute suicidality, anamnestic non-compliance, manifest addictive disorders or personality disorders (case example: the paranoid processing of the foreign body) or concomitant severe psychiatric illnesses.

Conclusion

In summary, Dr. Kägi rates VNS as a safe neurostimulation procedure for the treatment of TRD or major depression that combines well with other psychiatric treatments and has augmentative effects. It contributes to remission in the long-term course.

Source: Forum for Continuing Medical Education, Psychiatry and Psychotherapy Update Refresher, June 14, 2018, Zurich.

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