Vagus Nerve Stimulation (VNS)


VNS received FDA approval in July 2005 for adjunctive, long-term use in chronic or recurrent major depression in adult patients with an inadequate response to at least four antidepressant treatments. You could say it is an option after other treatments for depression has failed, these options for treatment resistant depression are summarized in another article on this blog: 9 steps for treatment resistant depression.
Time for an update. A review of important articles from a scientific point of view. Not an exhaustive literature search.

Vagus Nerve Stimulation for the long term efficacious?

Two unblinded trials have been published with (n=59) treatment resistant depressed patients. Over 30% were responders after 10 weeks. Response was defined as at least a 50% reduction of the Hamilton Depression Rating Scale, a depression severity scale. In a long term naturalistic follow-up of this study, 30 patients received an additional 9 months of stimulation. Response was sustained, and remission rates were significantly improved (from 17% to 29%). Remission is defined as a score on the HDRS of 10 or less, that is to say these patients were free of depressive symptoms. This suggests that the efficacy of VNS is probably something that takes time. Patients might benefit if VNS is given during a longer period of time.

Analysis of a 1 year follow-up from patients receiving additional VNS in an open label study showed that response increased per month during the 12-month follow-up. Response defined as decrease of the average HDRS score. This response criterion is very sensitive, clinical relevance is difficult to interpret.

The short term results from the placebo controlled study of VNS combined with usual standard of care the antidepressant effect of VNS could not be established. This study was performed before the open label long term study mentioned above.

Vagus Nerve Stimulation
What is VNS?
Bipolar electrodes are attached to the left vagus nerve within the neck. These electrodes are connected to a generator. This generator is a small device, it is implanted subcutaneously into the left chest wall. The generator is programmed to deliver mild electric pulses in continuous cycles, typically with 30 seconds of stimulation followed by 5 minutes off. The device can be set non-invasively by the treating physician who uses an external device to change the “dose”.
It could be that the antidepressant effect is achieved by influencing the amygdala and other limbic structures via projections from the vagus nerve.

The device and the electrodes on the vagus nerve are implanted during surgery by a neurosurgeon, mostly during general anesthesia.

Side-effects of Vagus Nerve Stimulation
During the short stimulation (30 seconds) voice alteration can occur as well as hoarseness, dyspnoe and cough.
There can be a slight cosmetic change in the appearance of the chest after generator implantation.

No clear acute relief of depression shown yet. In treatment resistant depression maybe an option for the longer term.

Literature used

1. Effects of 12 months of vagus nerve stimulation in treatment-resistant
depression: a naturalistic study.
Biol Psychiatry. 2005 Sep 1;58(5):355-63.

Rush AJ, Sackeim HA, Marangell LB, George MS, Brannan SK, Davis SM, Lavori P, Howland R, Kling MA, Rittberg B, Carpenter L, Ninan P, Moreno F, Schwartz T, Conway C, Burke M, Barry JJ.
Comment in:
Biol Psychiatry. 2006 Dec 15;60(12):1382; author reply 1382-3.

2. Vagus nerve stimulation for treatment-resistant depression: a randomized,
controlled acute phase trial.
Biol Psychiatry. 2005 Sep 1;58(5):347-54.
Rush AJ, Marangell LB, Sackeim HA, George MS, Brannan SK, Davis SM, Howland R, Kling MA, Rittberg BR, Burke WJ, Rapaport MH, Zajecka J, Nierenberg AA, Husain MM, Ginsberg D, Cooke RG.
Comment in:
Biol Psychiatry. 2006 Dec 15;60(12):1382; author reply 1382-3.

3. Vagus nerve stimulation (VNS) for major depressive episodes: one year outcomes.Biol Psychiatry. 2002 Feb 15;51(4):280-7.
Marangell LB, Rush AJ, George MS, Sackeim HA, Johnson CR, Husain MM, Nahas Z, Lisanby SH.

4. Vagus nerve stimulation (VNS) for treatment-resistant depression: efficacy, side
effects, and predictors of outcome.
Neuropsychopharmacology. 2001 Nov;25(5):713-28.
Sackeim HA, Rush AJ, George MS, Marangell LB, Husain MM, Nahas Z, Johnson CR, Seidman S, Giller C, Haines S, Simpson RK Jr, Goodman RR.

Other articles about Neurostimulation in treatment resistant depression on this blog:

1. ECT, for information about ECT this blog delivers a lot of articles, one here and the other over here.

2. More about Magnetic Seizure Therapy in a recent post on this blog.

3. About rTMS