Tips and pearls

VNS is FDA approved for TRD after four antidepression treatment failures, which include medications, psychotherapy, or ECT

Many insurance carriers deny this treatment in their policy despite FDA approval, likely due to the up-front cost, although will consider it upon appeal on a case-by-case basis

It has been studied in relatively non-comorbid, treatment-resistant patients. Therefore, to obtain outcomes seen in trials, similar patient selection is warranted

It takes a long time, comparatively, for VNS to become effective and must be dosed judiciously, similar to strategies employed in administering medications or even psychotherapy

Mechanism of action moment How does vns theoretically work?

Of course, there is no clear mechanism, but theoretically, it has preclinical evidence of antidepressant activity in several ways

Medications manipulate neurotransmitters and receptors to change neurochemical activity, which often changes neuronal electrical firing. VNS may actually use electricity to change neuronal firing directly, thus changing neurochemical activity

• – Antidepressants are known to increase chemical neurotransmitter concentrations and these change electrical neuronal firing

• – VNS appears to increase electrical neuronal firing with a resultant change in chemical neurotransmitter concentrations

• – As a net result from either approach, brain neurocircuitry functioning changes, and ideally, symptoms are alleviated

The left vagus nerve terminates in the brainstem and has secondary neural connections with brain areas associated with depression, such as the dorsal raphe (DR), LC, amygdala, insula, hypothalamus, and thalamus

Increased DR and LC firing rates have been noted during VNS use, suggesting facilitation of 5-HT and NE, similar to antidepressant effects

VNS promotes increases in neurotrophic factors that promote neuronal health and synaptic formation. This may allow for improved neurocircuitry function and alleviation of symptoms

VNS increases in brain activity were found in the bilateral orbitofrontal cortex (OFC), bilateral anterior cingulate cortex (ACC), and right superior and medial frontal cortex. Decreases were found in the bilateral temporal cortex and right parietal area. Regions of change were consistent with brain structures associated with MDD symptomatology and the afferent pathways of the vagus nerve

VNS therapy is associated with ventromedial prefrontal cortex (VMPFC) deactivation and produced greater right insula activation, which are similar to other antidepressant treatment findings

Finally, VNS may allow for deactivation in the VMPFC, which correlates with the antidepressant response to VNS therapy

These preclinical and human model studies suggest VNS has properties similar to other FDA-approved depression treatments and facilitates brain activity in areas of the brain noted to be dysfunctional in major depression.

Two-minute tutorial

Vns side effects

According to studies, during the first three months of VNS stimulation, adverse effects are no greater than 1.3%

The most common side effects are VNS stimulation-related

• – voice alteration (59%)

• – increased cough (24%)

• – neck pain (16%)

• – dyspnea (14%)

• – dysphagia (13%)

• – paresthesia (11%)

• – laryngismus (10%)

These side effects may dissipate over one year in up to 70% of patients

VNS is not associated with weight gain or sexual problems and has no drug–drug interactions

Surgical complications may include infection, general anesthesia reactions, and permanent left vocal cord paralysis

The device may be turned off via a computer in the office setting or by use of a magnet by the patient in the home setting, in order to stop stimulation and lower side effects

VNS device settings may be changed to lower side effects

• – The overall charge or its pulse width may be reduced to dampen the amount of electrical current reaching tissues in the neck and therefore lowering side-effect burden

• – The charge may be lowered to avoid side effects but dosing may be maintained by having the device activate every one to three minutes instead of every five minutes. This cumulative dosing may be used in patients who cannot tolerate higher charge doses to facilitate better VNS effectiveness

Programing the device is pain free. A hand-held computer sends programing signals via a radio frequency wand that transmits the new settings to the internal pacemaker, which sits internally below the scapula and medial of the axilla

Patients with VNS must avoid certain forms of high-dose ultrasound, lithotripsy, and magnetic resonance imaging (MRI) scans, as the device may malfunction or the VNS wires may overheat theoretically causing nerve damage

Figure 4.1. The VNS hand-held device and programing wand.