Researchers say a person’s quality of life should be taken into consideration when choosing treatments for depression.
People with depression may experience significant improvements in their quality of life through nerve stimulation, even if their depression symptoms don’t dissipate completely.
That’s the conclusion reached by researchers at Washington University School of Medicine in Missouri.
Their findings were announced online last month in The Journal of Clinical Psychiatry, published by the American Society of Clinical Psychopharmacology.
The team, led by principal investigator Dr. Charles R. Conway, a Washington University professor of psychiatry and director of the Treatment Resistant Depression and Neurostimulation Clinic, conducted a national study with nearly 600 patients.
The subjects all had depression that couldn’t be alleviated by four or more antidepressants, taken separately or in combination.
Conway and his team evaluated vagus nerve stimulators, devices similar to a pacemaker that sends mild, regular pulses of electrical energy to the brain via the vagus nerve.
The vagus, the longest cranial nerve, runs from your brain through your neck and into your chest and abdomen.
The Food and Drug Administration (FDA) approved vagus nerve stimulation (VNS) for treatment-resistant depression (TRD) in 2005.
When it was first approved, a number of scientists expressed concerns about the efficacy of the treatment.
Since then, further research and improvements in treatment have made vagus nerve stimulation more acceptable in the scientific community.
Recently, however, psychiatrists have recognized that evaluating only an antidepressant response to stimulation doesn’t adequately assess quality of life — which was the purpose of this latest study.
“When evaluating patients with treatment-resistant depression, we need to focus more on their overall well-being,” Conway told Healthline. “A lot of patients are on as many as three, four, or five antidepressant medications, and they’re just barely getting by. But when you add a vagus nerve stimulator, it really can make a big difference in people’s everyday lives.”
According to Conway’s study, as many as two-thirds of the 14 million people in the United States with clinical depression receive no relief from their first prescribed antidepressant.
Up to one-third don’t respond to subsequent treatment with other similar drugs.
The results for patients who received VNS were compared with those of others who received what the study referred to as “treatment as usual.” That could include antidepressant drugs, psychotherapy, transcranial magnetic stimulation, electroconvulsive therapy, or some combination.
The study followed 328 patients, two-thirds of them women.
Many participants had already used an antidepressant and had vagus nerve stimulators implanted.
The team compared that group’s results with those of 271 similar patients who received only treatment as usual.
Conway and his colleagues evaluated 14 categories of quality-of-life factors, including physical health, family relationships, ability to work, and overall well-being.
“On about 10 of the 14 measures, those with vagus nerve stimulators did better,” Conway said. “For a person to be considered to have responded to a depression therapy, he or she needs to experience a 50 percent decline in his or her standard depression score. But we noticed, anecdotally, that some patients with stimulators reported they were feeling much better even though their scores were only dropping 34 to 40 percent.”
“The device is implanted in the upper chest, underneath the clavicle,” Conway said. “The surgeon enters through the armpit or axilla. The surgery isn’t very complicated, and typically takes an hour and a half to two hours, and the patient goes home that day. The battery lasts 7 to 11 years, depending on the electrical settings. The greater the current, the quicker the battery drains.”
Vagus nerve stimulators received FDA approval in 1997 for epilepsy treatment. When researchers tested the therapy on those with epilepsy, they observed that some people who also had depression experienced fairly rapid improvements in their depression symptoms.
Conway began his VNS research in 2003. His initial work was with the pivotal study that led to FDA approval of the stimulator device for TRD, he said. The results were published in 2005.
His involvement in many subsequent studies include collaborations with Dr. Scott Aaronson, director of clinical research at Sheppard Pratt Health System in Baltimore and clinical associate professor of psychiatry at the University of Maryland School of Medicine.
Aaronson and Conway worked together on the two recent studies, including the latest research findings announced in August.
They also worked together on Aaronson’s study of nearly 800 patients who received VNS treatment for depression — published in 2017 in the American Journal of Psychiatry. Parts of that dataset from the 2017 study were used in the just-announced findings.
Aaronson has been involved with the development of VNS for severe TRD since 2003 when he was asked to take over the cohort of patients implanted with VNS who were enrolled in the original randomized trial of VNS for depression at the University of Maryland.
“Since then, I followed those 12 patients for over a decade,” Aaronson told Healthline. “I added another 40 patients participating in other VNS studies — including the Treatment Resistant Depression Registry reported by Dr. Conway and me — or implanted with independent support.”
“Given that worldwide only about 4,000 patients have received VNS for TRD, versus about 50,000 patients who have gotten it for treatment of refractory epilepsy, the 52 patients seen at the Sheppard Pratt Health System represent a significant number,” he added.
“Our experience has been heartening,” said Aaronson. “Many of those patients I have personally followed for over a decade. The patient I cited in my article with severe bipolar depression has gone from being hospitalized multiple times a year to twice in ten years. She also has gone from being unable to care for her son to being a functioning custodial parent.”
While not every patient benefits, the experience that the investigators have had is that most do, sometimes in subtle ways, Aaronson said.
When he and his colleagues analyzed the quality-of-life measure in implanted patients versus similar patients, they found that for the same drop in a depression rating, the VNS patients gained a greater improvement in their overall quality of life.
“The study that we have just reported on is a very special one,” Aaronson said. “It involved the largest cohort — 500 patients with VNS and 300 patients getting treatment as usual — of severe treatment-resistant depression ever reported and followed them for five years.”
“This was a monumental effort involving many people over a long time,” he added. “The fondest hope Dr. Conway and I have is that our work over these past 12 years will make VNS available to a larger patient population with severe difficult-to-treat depression.”
“Vagus nerve stimulation has been a tremendous amount of help where medications have failed,” said Dr. Brian Kopell, a neurosurgeon at Mount Sinai Health System in New York City, where he’s also the director of the Center for Neuromodulation and has used VNS to treat epilepsy. “It has a variety of uses, but sometimes it can take a couple of years to work.”
“One of the challenges is that VNS is not paid for by insurance because of the national, non-coverage decision by CMS [the Centers for Medicare & Medicaid Services, a federal agency],” Kopell noted. “People can’t get it paid for, so it doesn’t get used.”
However, Kopell told Healthline, the data coming out of VNS research, such as the Aaronson and Conway studies, has demonstrated VNS can be useful for patients with TRD.
Kopell said there hasn’t been a serious improvement in pharmaceutical treatment for depression in the past four decades.
Neuromodulation, electronic stimulation of the brain, has been around since the 1940s and reached its heyday in the late 1980s and early 1990s, he said.
“Neuromodulation has shown long-term effectiveness,” Kopell said. “Some patients have had success with implants for years. Aaronson’s 2017 study results were used as the basis for asking for a reversal of the CMS decision.”
In October 2017, LivaNova, a Houston-based company that manufactures VNS devices, made a formal request that the CMS reconsider its “national coverage determination” for VNS treatment of resistant depression.
In June, CMS officials announced that they may reverse their long-standing policy of not covering VNS for TRD.
Kopell said that after 20-plus years of working with VNS, he and his colleagues know the stimulation device is safe.
“Overturning the CMS decision so others can have access to this treatment will only help us learn how to do the procedure better, design better devices, and which patients to pick,” he said.
“Other forms of brain stimulation, such as transcranial magnetic stimulation, and deep brain stimulation, which is another surgical therapy that’s changed the way we treat movement disorders in this country, could be brought to bear on how we treat depression,” he added.
Kopell said all this research is a “huge opportunity” to learn about what these devices can do for the brain.
“The brain is an electrical organ like the heart,” he said. “Even though we can use drugs to treat the brain like we treat the heart, the most profound therapy is one that interacts with the electricity of the organ. The pacemaker for the heart does the same thing.
“These devices we’re developing now interact directly with this electricity to reduce symptoms and in some cases to potentially, functionally, cure these neurological conditions without side effects of the medication, which are profound.”
Conway also hopes to see the reversal of the current CMS non-coverage policy.
“Our short-term goal is to have Medicare cover this treatment for individuals with resistant depression,” he said. “Currently, Medicare and most private insurers do not cover this treatment, so it is only available to those with considerable financial means.”
Conway added, “We have worked hard to convince Medicare that this treatment is life-changing and even life-saving, as it lowers suicidal thinking. I hope that in five to seven years it will be available to those individuals afflicted with resistant depression.”