Vagal Nerve Stimulation for Treatment-Resistant Depression

Flavia R Carreno, Alan Frazer

Major depressive disorder (MDD) is prevalent. Although standards antidepressants are more effective than placebo, up to 35% of patients do not respond to 4 or more conventional treatments and are considered to have treatment-resistant depression (TRD). Considerable effort has been devoted to trying to find effective treatments for TRD. This review focuses on vagus nerve stimulation (VNS), approved for TRD in 2005 by the Food and Drugs Administration. Stimulation is carried by bipolar electrodes on the left cervical vagus nerve, which are attached to an implanted stimulator generator. The vagus bundle contains about 80% of afferent fibers terminating in the medulla, from which there are projections to many areas of brain, including the limbic forebrain. Various types of brain imaging studies reveal widespread functional effects in brain after either acute or chronic VNS. Although more randomized control trials of VNS need to be carried out before a definitive conclusion can be reached about its efficacy, the results of open studies, carried out over period of 1 to 2 years, show much more efficacy when compared with results from treatment as usual studies. There is an increase in clinical response to VNS between 3 and 12 months, which is quite different from that seen with standard antidepressant treatment of MDD. Preclinically, VNS affects many of the same brain areas, neurotransmitters (serotonin, norepinephrine) and signal transduction mechanisms (brain-derived neurotrophic factor-tropomyosin receptor kinase B) as those found with traditional antidepressants. Nevertheless, the mechanisms by which VNS benefits patients nonresponsive to conventional antidepressants is unclear, with further research needed to clarify this.