Vagus Nerve Stimulation for Rheumatoid Arthritis?

Bioelectric medicine is taking conditions outside psychiatry by storm.

As a medical device “maxi,” your editor over here at The Frontier Psychiatrists has been very interested in how we can reduce pain and suffering without drugs. I love drugs as much as the next guy who wrote a book called Inessential Pharmacology (amazon affiliate link).

My practice routinely prescribes the GammaCore non-invasive VNS (nVNS) device for Migraine, Hemicrania Continua, and Cluster Headaches. This is at my practice, Fermata, and at Acacia Clinics in Sunnyvale, as I’ve written about previously.

As an introduction for general audiences, I’ll preview the role of the Vagus Nerve—you may remember this from anatomy lab as Cranial Nerve X:

The vagus nerve forms intricate neural connections with an extensive number of organs, particularly the digestive system. The vagus nerve has a pivotal role as a fundamental component of the autonomic nervous system, exhibiting an essential effect. It establishes a direct link with the parasympathetic system, consequently eliciting the synaptic release of acetylcholine.

Autoimmune joint diseases include harrowing conditions like Rheumatoid Arthritis, Psoriatic Arthritis, Ankylosing Spondylitis, and others. Acetylcholine plays a vital role in these autoimmune conditions.

I have one of these disorders—specifically, Psoriatic Arthritis.

A picture of Owen Muir’s shin with Gutate Psoriasis, which I developed in my child psychiatry fellowship after exposure to strep from kiddos on the unit.

Over the past three years, I have become increasingly interested in the overlap of autoimmune conditions and psychiatric conditions. I have made 54 referrals to Rheumatologists based on presumptive diagnoses. Those diagnoses have been confirmed 53 times. Something was going on at this nexus of psychiatry and rheumatology.

However, it's difficult for logistical reason, to get dual specialization in these two areas of medicine. Part of this concerns the training necessary: a rheumatology fellowship requires an internal medicine residency, and the intern year of psychiatry only counts for one of those years. To specialize in psychiatry and also rheumatology, you must do a psychiatry residency, an internal medicine residency, and, subsequently, a rheumatology fellowship, which is another two to three years. At this point, after having done general psychiatry and child psychiatry fellowship, getting me to go back and do two years of internal medicine residency for the purpose of doing a rheumatology fellowship for another three is a bridge too far. I'm not sure this will be the case forever, but the older I get, the less a grueling internal medicine residency is going to seem appealing.

We have a problem in medicine: getting expertise across two medical disciplines is not easy. In part, you need knowledge to be a rheumatologist, including internal medicine-related things. It would be similarly challenging for me to specialize in vascular surgery if I did not have a general surgery residency. I don’t have this presumptively crucial knowledge. The counterpoint is that rheumatology is also deprived of the knowledge psychiatrists could bring.

Part of being a medical doctor is the definite awareness of what we know we don't know. The knowable thing? It is hard for those with expertise in psychiatry to learn about rheumatology, and it's hard for those with expertise in rheumatology to learn about psychiatry in any structured way. We're all—those interested in this crucial overlap— going to be “winging it.”

With those caveats aside, progress is being made in managing rheumatological conditions, which is borrowing heavily from approaches learned in interventional psychiatry. Today, I feature one. It’s called Vagal Nerve Stimulation (VNS).

VNS has been used in epilepsy in europe since 1994 and in the US since 1997¹. Its role in depression has had some ups and downs as well, which this article is glossing over for now. In Rheumatoid Arthritis (RA), success in treating patients has had a lot to do with relentless research translating bench findings to the bedside, and the data on VNS in RA is no different. In this most recent trial I’m reporting on, conducted at 41 sites across the US, patients who hadn’t gotten better enough were eligible:

Researchers aimed to assess the safety and efficacy of neuroimmune modulation using a cervical vagus nerve stimulation device implanted in patients with moderate to severe RA.

Eligible participants had previously failed treatment with at least 1 b/tsDMARD. [TFP: biologic or targeted synthetic disease-modifying antirheumatic drugs]

There is a treatment-resistant autoimmune disease, which is the sort of illness I’m used ot addressing in my psychiatric practice. The participants were enrolled in:

this randomized, double-blind, sham-controlled study (ClinicalTrials.gov Identifier: NCT04539964). They were randomly assigned in a 1:1 ratio to receive either active stimulation (treatment group) or sham control (control group) for 12 weeks, with all remaining on stable conventional DMARD treatment. The study became open-label after week 12, at which time control group participants crossed over to treatment until week 24.

They used a crossover design to take advantage of the statistical power of within-subjects study design:

Among the 242 participants (mean age, 56 years; 86% women), 122 received active treatment and 120 comprised the control group. A total of 97 patients from the treatment group and 98 from the control group remained in the study after crossover and were included in the 24-week analyses.

And the VNS treatment? It worked (defined at a 20% or greater improvement in the primary endpoint: the American College of Rheumatology response criteria (ACR20))

At week 12, 35.2% of patients from the treatment group and 24.2% from the control group achieved an ACR20 response (P=.0209; 95% CI, 0.6-23.1). After crossover, the percentage of responders further increased to 51.5% and 53.1% among the treatment and control groups at week 24, respectively.

The authors were able to suss out improvement above and beyond the placebo effect using this cross-over design. Psychiatry, take note!

It is worth noting the data includes a very broad confidence interval, but it suggests some potent responses in the cohort! It also didn’t just modulate pain or disability—the disease was getting better, according to the authors:

Low disease activity and remission status were achieved more frequently among the treatment vs control group.

Neuromodulation is getting an autoimmune disease better, and patients become stable and get off of some of the most expensive drugs that exist:

“At Week 24, 81% of patients were on stimulation therapy alone and free of added b/tsDMARD,” the researchers noted.

Well, ain’t that something?

1. Koopman, F., Schuurman, P., Vervoordeldonk, M., & Tak, P. (2014). Vagus nerve stimulation: A new bioelectronics approach to treat rheumatoid arthritis? Best Practice & Research Clinical Rheumatology, 28(4), 625-635. https://doi.org/10.1016/j.berh.2014.10.015