Improved Mood and Remission of Symptoms in Long-term Major Depression Using Vagus Nerve Stimulation

Amita R. Patel, MD, CMD, MHA, CPE; Shannon M. Wozniak, NP

In This Article


Major depressive disorder (MDD) affects about 18 million people in the United States,[1]and most patients who have one major depressive episode are likely to have another within 5 years.[2]Overall, as many as 20% of patients with major depression do not respond to 2 or more adequate treatment regimens for depression.[3,4] The treatment options for these patients have traditionally been limited. Treatment typically entails trials of different antidepressants, and in severe cases, use of electroconvulsive therapy (ECT). But this type of "treatment as usual" often fails to bring about remission. One prospective study looked at the long-term outcomes of patients with treatment-resistant depression (TRD) who continued with ongoing "treatment as usual." After 2 years, more than 90% of the 124 patients continued to experience substantial levels of depressive symptoms; 65% showed no response at any point and 81% showed no remission at any point.[5]

These findings suggest that the vast majority of patients with TRD do not experience long-term benefits from traditional therapeutic strategies. These patients continue to have decreased quality of life and the debilitating symptoms associated with major depression.

A relatively little-known treatment for TRD, vagus nerve stimulation (VNS TherapyTM, Cyberonics, Houston, Texas), was approved by the US Food and Drug Administration for this indication in July 2005.[6] The therapy consists of an implanted, disk-shaped generator that provides timed and measured pulses via electrodes to the left vagus nerve. The stimulation dose is set by using an external telemetric wand and software to stimulate the vagus nerve at regular intervals. During routine office visits, physicians can adjust the timing and amount of stimulation the patient receives (Figure). Because of its nature, the therapy assures patient adherence.


Diagram of vagus nerve stimulation device. (A) A small pacemaker-like pulse generator is implanted under the skin in the left chest area. Timed and measured pulses are generated and pass through a thin, flexible wire to electrodes that stimulate the left vagus nerve. (B) The stimulation dose can be adjusted by an external telemetric wand and special software during routine office visits. (Adapted from

VNS therapy is indicated for patients 18 years of age or older who are unable to achieve sustained remission after 4 or more adequate trials of antidepressants. A 10-week randomized, controlled study of 235 outpatients with long-term unresponsive MDD (n = 210) or bipolar disorder (n = 25) reported a higher response among patients receiving VNS therapy than among those receiving sham therapy on the 24-item Hamilton Rating Scale for Depression (HRSD24), the patients receiving VNS also had a statistically significant response on the Inventory of Depressive Symptomatology-Self-Report (IDS-SR30).[7]A 12-month naturalistic follow-up study compared the effect of a full year of adjunct VNS therapy in all 205 evaluable patients, with those previously receiving sham therapy switched to active therapy. The primary analysis revealed a significant reduction in HRSD24 scores over time and at exit (mean monthly improvement 0.45; P < .001) as well as significant reductions over time in IDS-SR30 scores (mean monthly improvement, 0.52; P < .001).[8] These findings suggest that the benefit of VNS therapy may not be realized until several months into therapy.

Patients in this pivotal trial of VNS therapy were a mean 46.5 years of age and had a mean duration of illness of 25.5 years.[8] Could the therapy be effective for a considerably older woman with a duration of illness longer than most of the study sample? We report the case of a postmenopausal woman with long-standing MDD and a history of poor response to antidepressants and ECT. Her condition was further complicated by comorbid conditions, including obesity, hypertension, hypercholesterolemia, gastroesophageal reflux disease, hypothyroidism, and osteoarthritis.


Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.
Post as: