Electronic Spring 2024 | Issue 58

Where Physiology and Psychiatry Collide: A Brief Review of 2 New (to me) Treatments

By: Luke Lammers

As a 3rd year medical student, I am finally exposed to clinical medicine and witnessing the “art” of being a physician. In contrast, during my first two years of medical school, I was inundated with a multitude of mechanisms, pathways, and anatomy that all boiled down to a clear, black or white, right or wrong, multiple-choice answer. For many specialties, these mechanisms that occupied my psyche still prove useful. For example, family medicine practitioners know that ACE inhibitors block the RAAS cascade to lower blood pressure. The infectious disease physician understands that the cephalosporins bind to penicillin binding protein to interfere with peptidoglycan formation, and all the ramifications of this as it pertains to treating infection. Psychiatry, however, does not adhere as closely to these physiologic pathways. The waters are muddied by human experience, a lack of an objective measure of emotions and spiritual well-being, and the difficulty of understanding the complexities that lie within the brain and underlie our consciousness. It was precisely these muddy waters that enthralled me with psychiatry in the first place. It was a specialty in which so much more was yet to be discovered, and I would be able to learn and innovate alongside the field itself.

This is why I was so interested in learning more about two treatments that I heard about within the last 2 months. First, while on an ENT rotation, I witnessed the placement of a vagal nerve stimulator for treatment resistant depression as part of an ongoing clinical trial. In an uncontrolled 2-year follow-up trial used to gain FDA approval for the procedure, 40-45% of patients experienced at least 50% symptom improvement. However, other trials, which studied the treatment for 10-12 weeks, showed less promising results.1 This discrepancy led to some controversy surrounding the FDA approval of this treatment. With an out-of-pocket cost of $39,000 and a difficult process to get insurance to cover the procedure, this treatment remains inaccessible to many patients. However, I look forward to following the future research of this intervention.

A more promising treatment came to my attention after I met Dr. Lipov, an anesthesiologist who specializes in pain management, who is pioneering a new treatment for PTSD. Of note, one of Dr. Lipov’s main focuses presently is to rename PTSD to “PTSI” or “post-traumatic stress injury” in an attempt to remove the stigma around the diagnosis. For the purposes of this article, I will continue to use the term “PTSD”. He has been treating his PTSD patients with a procedure that he coined “Dual Sympathetic Reset” (DSR), in which bupivacaine is injected into the stellate ganglion on the left at 2 separate levels of the cervical spine to achieve a nerve block, then on the right side if indicated. This is performed as a method of “resetting” the sympathetic nervous system (SNS), which is chronically overactive in patients with PTSD.2 It has also been shown that levels of norepinephrine, a main neurotransmitter in the SNS, are higher in those with PTSD,3,4 further emphasizing the hypothesis of SNS hyperarousal in PTSD. The idea is that by breaking the chronically active feedback loop of the SNS using the nerve block, the symptoms of PTSD will be ameliorated. And this is exactly what has been found in preliminary trials. In a 2019 study of 113 participants, published in JAMA, Olmsted et al. found that CAPS-5 PTSD score decreased 12.6 points in those treated with 2 stellate ganglion blocks performed 2 weeks apart, compared to 6.1 in those treated with the placebo. It should be noted, however, that the nurses and physicians were not blinded to the treatment arm. Further double-blinded, placebo-controlled studies are currently underway at NYU. Given the relatively low risk of the procedure, and an overall lack of side effects besides the expected mild unilateral Horner’s Syndrome, this treatment option is worthy of further research and attention.

The theory of SNS overactivation in PTSD then begs the question, would vagal stimulation work for PTSD? It seems that this could be the case. As Dr. Lipov described, “Either lower the [sympathetic] river or raise the [parasympathetic] bridge.” Multiple studies have shown that transcutaneous vagal nerve stimulation in those with PTSD does modulate autonomic responses such as peripheral vasodilation, heart rate, and other measures,5,6 which provides theoretical promise for its use in the treatment of PTSD. Though not all experimental treatments come to fruition, learning about their mechanism of action helps to elucidate the pathogenesis of mental illness. The continued innovation in the field fuels my passion for Psychiatry and excites me for its future.

References

  1. O’Reardon, J. P., Cristancho, P., & Peshek, A. D. (2006, May). Vagus nerve stimulation (VNS) and treatment of depression: To the brainstem and beyond. Psychiatry (Edgmont (Pa. : Township)). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2990624/ 

  2. Morris, M. C., & Rao, U. (2013, February). Psychobiology of PTSD in the acute aftermath of Trauma: Integrating Research on Coping, HPA function and sympathetic nervous system activity. Asian journal of psychiatry. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3565157/ 

  3. Pan X, Kaminga AC, Wen SW, Liu A. Catecholamines in Post-traumatic Stress Disorder: A Systematic Review and Meta-Analysis. Front Mol Neurosci. 2018 Dec 4;11:450. doi: 10.3389/fnmol.2018.00450. PMID: 30564100; PMCID: PMC6288600.

  4. Geracioti TD Jr, Baker DG, Ekhator NN, West SA, Hill KK, Bruce AB, Schmidt D, Rounds-Kugler B, Yehuda R, Keck PE Jr, Kasckow JW. CSF norepinephrine concentrations in posttraumatic stress disorder. Am J Psychiatry. 2001 Aug;158(8):1227-30. doi: 10.1176/appi.ajp.158.8.1227. PMID: 11481155.

  5. Lamb DG, Porges EC, Lewis GF, Williamson JB. Non-invasive Vagal Nerve Stimulation Effects on Hyperarousal and Autonomic State in Patients with Posttraumatic Stress Disorder and History of Mild Traumatic Brain Injury: Preliminary Evidence. Front Med (Lausanne). 2017 Jul 31;4:124. doi: 10.3389/fmed.2017.00124. PMID: 28824913; PMCID: PMC5534856.

  6. Gurel, N. Z., Wittbrodt, M. T., Jung, H., Shandhi, M. H., Driggers, E. G., Ladd, S. L., Huang, M., Ko, Y.-A., Shallenberger, L., Beckwith, J., Nye, J. A., Pearce, B. D., Vaccarino, V., Shah, A. J., Inan, O. T., & Brenner, D. (2020, October 20). Transcutaneous cervical vagal nerve stimulation reduces sympathetic responses to stress in posttraumatic stress disorder: A double-blind, randomized, Sham controlled trial. Neurobiology of Stress. https://www.sciencedirect.com/science/article/pii/S2352289520300540