VNS (Vagus Nerve Stimulation)
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Q:  VNS (Vagus Nerve Stimulation)

Dr Phelps,

I have finally seen (read) mention of VNS (Vagal Nerve Stimulation) mentioned in your questions but, not directly.

What I need to know is, what has the latest research demonstrated in treating Bipolar Disorder? Specifically rapid cycling. I read an article last week that Cyberonics Inc., in conjunction with The Texas Southwestern Medical Center in Dallas would be conducting a study specifically w/VNS for rapid cyclers. They were to take a year to moniter (this was in July of 2001) results. I'm guessing that by now something is known? I really need to know as I'm allergic to almost all anticonvulsants!

Here is the link to where I read this particular article:

Please note that I've read about this possibility about 2 years ago and have been frantically looking (on and off) for as much info regarding this possibility. Any information or resources you can provide would be greatly appreciated!

Thank you,

Dear Ms. A -- 
Looking for their results, the most recent report I could find searching PUB MED for "vagus bipolar" is Dr. Marangell's group (the one the article says was studying this), as part of a multi-center collaboration (e.g Dr. George and Dr. Nahas are from South Carolina), saying: 

This open pilot study of vagus nerve stimulation (VNS) in 60 patients with treatment-resistant major depressive episodes (MDEs) aimed to: 1) define the response rate; 2) determine the profile of side effects; and, most importantly; 3) establish predictors of clinical outcome. Participants were outpatients with nonatypical, nonpsychotic, major depressive or bipolar disorder who had not responded to at least two medication trials from different antidepressant classes in the current MDE. While on stable medication regimens, the patients completed a baseline period followed by device implantation. A 2-week, single blind, recovery period (no stimulation) was followed by 10 weeks of VNS. Of 59 completers (one patient improved during the recovery period), the response rate was 30.5% for the primary HRSD(28) measure, 34.0% for the Montgomery-Asberg Depression Rating Scale (MADRAS), and 37.3% for the Clinical Global Impression-Improvement Score (CGI-I of 1 or 2). The most common side effect was voice alteration or hoarseness, 55.0% (33/60), which was generally mild and related to output current intensity. History of treatment resistance was predictive of VNS outcome. Patients who had never received ECT (lifetime) were 3.9 times more likely to respond. Of the 13 patients who had not responded to more than seven adequate antidepressant trials in the current MDE, none responded, compared to 39.1% of the remaining 46 patients (p =.0057). Thus, VNS appears to be most effective in patients with low to moderate, but not extreme, antidepressant resistance. Evidence concerning VNS' long-term therapeutic benefits and tolerability will be critical in determining its role in treatment-resistant depression.

As you can see, the bipolar group was folded into the larger 60-patient sample.  They found that people who had not improved with many, many antidepressant trials didn't get better from VNS either -- but they don't comment in the abstract on the bipolar group separately.  Here's the link to this abstract in case you have access to a librarian who can hunt up the full article.  

I think the data is just slightly better, if you want to watch it closely over the next year or so, for another treatment approach called rTMS:  repetitive Transcranial Magnetic Stimulation.  Here's a basic intro', and here's an article on TMS in bipolar depression:  not really great results, but there's been some question as to whether "sham" is really sham for this procedure, as it too activates the cortex somewhat, though less than "active" treatment; and note that 4 people in each group did improve substantially (there is no separate placebo group, that's what "sham" is supposed to be).  

Anyway, you can see that TMS is being studied a little bit more specifically for bipolar is this report, just trying to establish safety before going on, and that at least looks good:  no induced mania (whereas this has already been reported for VNS).  TMS also has the advantage of the fact that by changing the dosing (frequency and intensity) you can actually damp down overactive cortex, as well as stimulating underactive -- selectively.  There seems to be a crucial difference between the right and left frontal lobes in terms of how they respond to TMS (e.g the Israeli research group's work). 

I hope that helps some. 

Dr. Phelps

Published June, 2003


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