Vagus Nerve Stimulation for Treatment-Resistant Depression
Abstract & Commentary
Source: Rush AJ, et al. Vagus nerve stimulation for treatment-resistant depressions: A multicenter study. Biol Psychiatry 2000;47:276-286.
Depression is now being recognized as a chronic or recurrent lifelong illness, rather than an isolated single episode from which lasting recovery can be expected. Although depression is most often a treatable illness, 5-15% of major depressive episodes last greater than two years and up to 1.5% of the general population suffer chronic or severe depressions. At least 10-20% of all depressed patients do not have satisfactory sustained response to present treatments.
Vagus nerve stimulation (VNS) is an approved therapy for treatment-resistant epilepsy. The current study examined the safety and potential antidepressant effects of VNS for treatment-resistant depression in an open pilot study. The idea of using VNS as a treatment for clinical depression was initially based on clinical observations of improved cognition and mood during studies of patients with epilepsy, even in subjects who did not experience improved seizure control. Further rationale for the use of VNS in the treatment of depression is provided in a companion article,1 which notes that incoming sensory (afferent) connections of the left vagus nerve provide direct projections to many of the brain regions implicated in neuropsychiatric disorders, and that VNS has been shown to effect key neurotransmistters, including serotonin, norepinephrine, GABA, and glutamate.
In the current study, adult outpatients (n = 30) with nonpsychotic, treatment-resistant, major depression or bipolar depression, who had failed robust trials of standard treatment were implanted with the neurocyberonics prosthesis (NCP) to deliver preprogrammed stimulation to the left cervical vagus nerve (10th cranial nerve). The NCP system includes an implantable and multiprogrammable pulse generator that is surgically implanted under the skin of the chest. The generator, which delivers electrical signals to the left vagus nerve, is programmed via a wand attached to a computer, much like a pacemaker.
The 12-week study included a two-week recovery period, two weeks of stimulation adjustment, and eight weeks of fixed-dose stimulation, after which patients may continue to receive longer-term follow-up and ongoing VNS treatment. Patients on antidepressant medications maintained a stable antidepressant medication regimen for at least four weeks prior to the initial baseline visit and throughout the study (medication decreases, but not increases, were allowed).
Response was defined a priori as a greater than 50% reduction in the mean Hamilton Depression Rating Scale (HRSD28) score. Of note, and appropriate to such a study, the patient population was severely ill; over their lifetimes, patients averaged 18.4 (SD = 7.3). Sixty-three percent had received electroconvulsive therapy in their lifetime. Overall, there was a 40% response rate using a greater than 50% reduction in baseline HRSD28 total score to define response.
At exit, according to the CGI-I, 3% were minimally worse, 27% were unchanged, 30% were minimally improved, 20% were much improved, and 20% were very much improved at acute phase study exit. When complete response is defined as exit HRSD28 less than 10, 17% of patients responded completely. No patient discontinued the acute study due to adverse events. Adverse events were no different than those expected from previous studies of VNS in patients with epilepsy.
Comment by Lauren B. Marangell, MD
This is the first report of VNS in a psychiatric population. Response rates of 40%, as well as the 17% complete response (remission) rate (exit HRSD28 less than 10), suggest efficacy in this cohort of individuals with very treatment-resistant depression. As Rush and colleagues clearly note, the small sample size and open design mandate that these data be considered preliminary. However, the chronic, disabling, and treatment-resistant nature of the depressive episodes in this patient sample make it unlikely that the response seen was unrelated to the therapeutic intervention. Given the significant number of patients that fail to respond to standard treatments, positive data for a novel intervention is remarkable, and offers hope for the many individuals who have come to believe that there is no hope for improvement. The key question will be longer-term efficacy and possibly use in other disorders that also involve brain circuits that are affected by VNS, such as obsessive compulsive disorder.1 The use of a surgically implanted device to treat psychiatric disorders is likely to raise criticism. However, those who object to an invasive procedure to treat severe depression perhaps underestimate the suffering and disability caused by this disease.
Reference
1. George MS, et al. Vagus nerve stimulation: A new tool for brain research and therapy. Biol Psychiatry 2000; 47:287-295.
You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
- Award-winning Medical Content
- Latest Advances & Development in Medicine
- Unbiased Content