Clinical and Research News
Anesthetic Injection Tested to Treat PTSD
Psychiatric News
Volume 45 Number 19 page 18-29

A one-shot cure proposed to treat a major chronic psychiatric disorder is raising cause for hope, but it is also arousing much skepticism. Several recent case reports suggest that injecting an anesthetic into nerves in the neck could rapidly eliminate symptoms of posttraumatic stress disorder.

The procedure's leading proponent said that he has had success with the technique and is ready to move on to clinical trials. However, other experts argue for greater caution and more preliminary research.

The stellate ganglion block is a well-known, if not entirely routine, procedure in which an anesthetic is injected next to the C7 vertebra. Anesthesiologists use it to manage pain in the sympathetic nervous system when other treatments have failed.

Eugene Lipov, M.D., an anesthesiologist at Advanced Pain Centers in Hoffman Estates, Ill., has used stellate ganglion block to treat pain and hot flashes and now says that it could be useful for PTSD.

"Clinical effects can be seen in 30 minutes," Lipov told Psychiatric News. "I hope that as more data becomes available, it will speak for itself and be a good tool in treating PTSD."

Reports like that have reaped some attention in the popular press, driven in part by the need to treat many military members returning from Iraq and Afghanistan with symptoms of PTSD ("Jab to the Neck Treats PTSD?" said New York television station WABC). Lipov testified in July before the House Committee on Veterans Affairs.

About 35 PTSD patients have been treated so far, and all but four or five have experienced positive results, Lipov said.

Some patients required more than one injection after the initial effects wore off, suggesting that the procedure did not permanently stop their PTSD.

The overall published record is still thin, however.

One study from 1947 described use of stellate ganglion block to treat depression.

A case published in 1990 used stellate ganglion block as one of several therapies for an adolescent with a combination of pain and PTSD.

A Finnish researcher suggested in 2003 that severe anxiety and social phobia might be alleviated by a reversible sympathetic block.

Following up on Lipov's work, an Army physician, Sean Mulvaney, M.D., and colleagues from the Uniformed Services University of the Health Sciences in Bethesda, Md., published two cases in the June Pain Practice. Lipov describes four cases in a chapter in a forthcoming book on PTSD.

Those published results have been uniformly positive, but other anesthesiologists and experts on PTSD want more evidence before declaring victory.

"It's strange, given the complexity of PTSD and its associated abnormalities in brain structure and neuromodulator function, that an intervention taking place outside the brain could produce a miraculous cure," said psychiatrist Matthew Friedman, M.D., Ph.D., in an interview. Friedman is executive director of the Department of Veterans Affairs' National Center for PTSD in White River Junction, Vt., and a professor of psychiatry and pharmacology at Dartmouth Medical School.

"Fixing PTSD with one little thing seems difficult to understand right now," said Marek Brzezinski, M.D., Ph.D., an associate professor of anesthesiology at the University of California, San Francisco, and the San Francisco VA Medical Center. "While the [stellate ganglion block] may be potentially useful, more testing and experience are necessary before we can recommend it."

Stellate ganglion block is not without risk because the ganglion lies close to the lungs, important blood vessels, and other nerves, said Brzezinski, a spokesperson for the American Society of Anesthesiologists.

Brzezinski and Friedman also have questions regarding Lipov's hypothesis about a possible mechanism of action.

Lipov suggests that stress (in this case, from a traumatic event and its aftermath) stimulates nerve growth factor that acts on the stellate ganglion to promote sprouting and new neuronal growth. Sprouting leads to increased production of norepinephrine, which leads to increased anxiety and continuation of PTSD. He cites research indicating neural pathways connecting the stellate ganglion to the hypothalamus, the central nucleus of the amygdala, and, ultimately, to other areas of the brain.

Injecting an anesthetic into the stellate ganglion decreases nerve growth factor levels, reducing sprouting and thus norepinephrine. This neuroremodeling may occur in as little as 24 hours, and effects have lasted through at least one year of follow-up, he said. "It reboots the nervous system," said Lipov.

However, said Brzezinski, nerve growth factors either go down or remain the same in patients or animals subject to stress, and another neurotrophin, brain-derived neurotrophic factor (BDNF), is significantly reduced in patients with PTSD.

"I have never heard of the idea of nerve sprouting in the stellate ganglion in PTSD patients," he said. "It's difficult to say how this would work. Also, [Lipov and Mulvaney] have reported a quick response, within minutes, but changes involving nerve growth produced by neurotrophins take time to work. So I'm not sure I agree with his hypothesis at this time."

The block may simply reduce sympathetic drive, said Brzezinski. "PTSD is an anxiety disorder with an incredible sympathetic discharge over a long period of time, so an anesthetic affecting that discharge may partially affect PTSD. But this is a hypothesis that needs testing."

FDA approval is not needed for use of the block per se, since all equipment and the anesthetic marcaine were approved long ago, said Lipov. Nevertheless, he did request and receive the FDA's clearance to use the stellate ganglion block for PTSD. The FDA's letter paved the way for institutional review board approval.

He is continuing work beyond his case series with a single-blind controlled study of 30 patients. (The study cannot be double-blinded because the normal effects of the stellate ganglion block include responses, like eye droop, visible to the treating physician.) Half the patients will receive marcaine, half will get sham injections of saline.

Lipov expects to complete gathering data within six months. He has applied for, but not yet received, external grant funding, he said.

He may have to develop more evidence on his own before that happens, however.

"I'm frankly very skeptical—but I'm open to further study," said Friedman.

He would like to see a more solid theoretical basis, good scientific evidence, and some animal research, citing the case of D-cycloserine, an old tuberculosis drug that also mediates new learning in NMDA receptors. D-cycloserine shows promise of accelerating the pace of Prolonged Exposure Therapy for PTSD.

"There's a neurobiological understanding of where and how the receptor works, evidence from animal studies about how it affects learning, and clinical studies observing its effects in acrophobia and social phobia," he said.

There are also good animal models of fear conditioning, said Friedman. "So I'd like to see some research [on stellate ganglion block] looking at these systems in animals."

So far, the six published cases are all drawn from relatively young people (aged 23 to 56), with recent trauma, and little comorbidity, compared with the typical PTSD patient of longer duration with more comorbidities, he noted.

More information in varied patient populations, with varying ages, comorbidities, and time since onset, along with data about side effects will be needed before this treatment can be recommended, said Brzezinski. Recognized measures of PTSD symptom severity, like the PTSD Check List, must be used before and after treatment to gauge outcomes, said Friedman.

Describing the full range of outcomes is critical, too.

"It is important to share both the successes and the failures," said Brzezinski. "It's too early to say if it works or doesn't from a few encouraging experiences. We must continue to look at stellate ganglion block from a meticulous scientific perspective."

Certainly the need is there, as everyone who spoke with Psychiatric News agreed.

"Veterans deserve every effort to push the field ahead, but they also deserve that we not expose them to any inadequate treatment and not hype treatment before we have stronger data or they will lose trust in the medical profession," said Brzezinski.

An abstract of "The Use of Stellate Ganglion Block in the Treatment of Panic/Anxiety Symptoms With Combat-Related Posttraumatic Stress Disorder; Preliminary Results of Long-Term Follow-Up: A Case Series" is posted at <http://onlinelibrary.wiley.com/doi/10.1111/j.1533-2500.2010.00373.x/abstract>.blacksquare

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