1. Home>
2. Specialties>
3. Psychiatry>
4. Feature

Emerging Perspectives: Does VNS Work in Refractory Depression?

Three studies provide inconclusive evidence.

Vagus nerve stimulation (VNS), used to treat epilepsy since 1997, received FDA approval as an adjunctive therapy for treatment-resistant depression. Three multicenter studies, supported by the manufacturer of the implantable VNS device and conducted by the same research team, have now examined the device’s short- and longer-term efficacy in a group of 222 patients with clearly refractory depression (current episodes had failed to respond to 2–6 adequate trials of treatment, including ECT in one third of patients). All patients underwent surgery for device implantation.

All patients had experienced at least four lifetime depression episodes, or the current episode had lasted at least 2 years (average illness duration, 25.5 years). About 10% of patients had bipolar disorder.

In the first study, the primary outcome measure was response on the Hamilton Rating Scale for Depression (defined as 50% improvement in scores). Patients were randomized to 10 weeks of active or sham VNS (the device was turned off for sham VNS) added to multiple medications that patients were already taking. Between-group differences in HRSD response rates were not significant.

In the second study, 205 of the patients were treated openly with active VNS for another 9 months (i.e., the stimulator was turned on in all patients). The primary outcome measure was the change in HRSD scores. Scores progressively decreased to a statistically significant degree over the year of follow-up (mean decrease, 26%). Fifty-five patients responded (27%), and 32 remitted (15%); findings were similar on some secondary measures. Most responders had a sustained response (50% improvement at one monthly visit and 40% improvement at two others within the last 3 months of the study). Still, 30 patients deteriorated, and 7 attempted suicide (3 for the first time).

In the third study, the researchers compared reductions in patients’ scores on a secondary measure with those among 124 treatment-as-usual (TAU) patients with similar levels of depression enrolled in a naturalistic study of healthcare costs at some of the same centers. At 12 months, the VNS group had significantly greater score reductions than did the TAU group (23% vs. 11%). HRSD score reductions were similar (29% vs. 18%). The HRSD response rate with VNS was double the rate with TAU.

Comment: Although adjunctive VNS is not particularly effective acutely, response might increase with continued treatment. Despite the second study’s statistically significant results, these studies have some drawbacks. Average reductions in depression scores and response/remission rates were mediocre, corrections were not made for multiple comparisons, the definition of sustained response would not satisfy many patients, subjects from different studies were compared, and open treatment was used without control groups.

A few patients who have not responded to other treatments might benefit from VNS. However, clinicians should avoid exposing large numbers of patients to this expensive treatment which requires surgical implantation — especially because many will not do well. We need additional research to determine specific predictors of benefit, any overlap between ECT nonresponse and VNS nonresponse, and any meaningful improvement in functioning.

— Steven Dubovsky, MD

Published in Journal Watch Psychiatry November 2, 2005

Citation(s):

Rush AJ et al. Vagus nerve stimulation for treatment-resistant depression: A randomized, controlled acute phase trial. Biol Psychiatry 2005 Sep 1; 58:347-54.

• Medline abstract (Free)

Rush AJ et al. Effects of 12 months of vagus nerve stimulation in treatment-resistant depression: A naturalistic study. Biol Psychiatry 2005 Sep 1; 58:355-63.

• Medline abstract (Free)

George MS et al. A one-year comparison of vagus nerve stimulation with treatment as usual for treatment-resistant depression. Biol Psychiatry 2005 Sep 1; 58:364-73.

• Medline abstract (Free)