When meds fail, magnetic therapy shows promise for treating depression

6:54 PM, Apr. 27, 2012 

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Dr. Amit Anand demonstrates the TMS device on Patty Harshaw, his department's TMS coordinator. / Doug McSchooler / For the Star

Written by

Shari Rudavsky

 

The depressed part of Ruth Schwer's brain told her that nothing would help, nothing would break through the stifling malaise. She had tried medications. Each worked for six months to a year, but then, the effect would wear off, and she would plummet back into darkness.

Still, the thinking side of her brain told Schwer, 43, to keep looking for a treatment.

"I felt more and more desperate," she said. "But the rational part says that you've experienced this before, you know it will change."

Then, she found a therapy unlike any other she had tried -- transcranial magnetic stimulation, known as TMS.

The treatment delivers magnetic pulses that produce electricity in her brain. While no one knows for sure how it works, the pulses appear to correct a deficit in the brain's chemical makeup, which over time results in a lifting of the depression.

Approved for use by the Food and Drug Administration four years ago, TMS gives psychiatrists their first-ever tool for patients for whom medications don't work or produce too many side effects. It is not as drastic as electro-convulsive therapy, which can interfere with a person's memory and is usually reserved for people with the most severe forms of depression.

For patients like Schwer, who lives on the Northwestside, TMS can be life-changing.

Schwer has a master's degree and a full-time job. But since puberty, she has grappled with periods of depression that leave her bedridden and isolated.

In the summer of 2010, she decided to try the treatment, which consists of half-hour or so sessions every day for four to six weeks.

Patients settle into a spa chair, and the doctor positions the magnet, a C-shaped device a little larger than the span of your hand, over the left side of the skull, next to the part of the brain that governs mood.

The NeuroStar TMS machine then administers treatment for four seconds, rests for 26 seconds and fires again. The pulses are thought to stimulate the neurons in the area, which prods them to release neurotransmitters, which over time will improve mood in many patients.

Depression doesn't stem from a lack of one chemical in the brain but from the workings of the brain's circuit as a whole, doctors think.

"It's the same as how electricity is produced through turbines. . . . The brain is also a conducting organ," said Dr. Amit Anand, director of the TMS and mood disorders programs at Indiana University Health. "It is a different way of thinking about depression. . . . We can straight away treat the organ, the brain, which is involved in depression, rather than the whole body."

The treatment sensation is not pleasant, say some who have gone through it. It's like "noogies," said Dr. Christopher Bojrab, a psychiatrist in private practice in Indianapolis, who has tried it.

As compared with other therapies, including medications, side effects other than the discomfort are minimal, experts say. A very small number of cases have resulted in seizures.

Schwer recalled it feeling more like a woodpecker sitting inside her temple.

"The odd thing is that the pressure was coming from the inside of your head, not the outside," she said.

Over time, however, she got used to the sensation, and it did not bother her.

Then about the third week of treatment, she woke up one day and realized she was smiling.

"I realized I had the freedom to direct my attention to where I wanted it to go," she said. "Having the option to experience happiness and joy, I felt like something had definitely changed for me."

Schwer remains on medication, but at a lower dose. And most exciting, her prescription has not changed for more than a year. She said it's easier to interact with strangers or try new things, like signing up for an African drumming class.

In the past year, she was also able to undergo surgery to correct her congenitally malformed hips.
"I felt like there was a point to getting better," she said. "In my previous mental state, I would have said, 'Yes, I'm in pain, but what does it matter? It's not going to get better, you just have to live with it.' "

TMS may not be for everybody. Treatments aren't cheap, and many insurers don't cover it. Patients can expect to pay upwards of $6,000.

Nor does it help everybody. To qualify, one must have tried and failed to address the depression with medication.

About a third of those people who try TMS will see their symptoms completely disappear, said Dr. Mark George, a spokesman for the American Psychiatric Association, who has studied TMS since 1993.

Once people have undergone treatment, they may need a follow-up session or two, but some people enjoy results for years. And, if they return five or six years later, undergoing therapy again often helps, said George, a research psychiatrist at the Medical University of South Carolina.

Bojrab, who has been offering the therapy for about two years, said that none of the 20 patients he's treated has returned. Out of those 20, three showed no response, half had a good response, and seven enjoyed complete remission; some even stopping their medications.

Before she underwent the treatment at IU Health, Jan Tobias, 56, had hoped she would fall in the latter camp. More than halfway through, it became clear that would not be the case.

Nor did she experience what she would define as a complete turn-around. Still, partway through, the Nappanee grandmother, who has battled depression most of her life with little relief from pharmaceuticals, saw a change.

"I had days of a difference where it was night and day. It was like opening my eyes for the first time," she said. "Everything was brighter, everything was new. I was thinking, 'Is this how it's really supposed to be?' Then the next day or two days, I would fall back."

But her husband said he had noticed a difference. And now, after going through the treatments last summer, Tobias can function once more.

"It's a new world for me . . . The main thing is, all you want to do is gain hope, and the rest can come later," she said. "That was my main goal, to gain hope in life."

http://www.indystar.com/article/20120429/LIVING01/204290304/When-meds-fail-magnetic-therapy-shows-promise-treating-depression

When Supplements Become Dangerous

Bulletin

When Supplements Become Dangerous

They're not as harmless as you may think

by: Peter Jaret | from: AARP Bulletin | April 4, 2012

A year after undergoing a kidney transplant, the 74-year-old patient was doing remarkably well. But when doctors reviewed his blood tests, they discovered an alarming mystery: Levels of the drug that was preventing the patient’s body from rejecting the transplanted kidney had dropped significantly. “We had no idea why at first,” says Joseph Boullata, associate professor of pharmacology and therapeutics at the University of Pennsylvania School of Nursing.

See also: Slideshow of 10 supplements that can interfere with your prescription meds — ginseng, kava, licorice and more.



When taken orally, aloe vera may interact with medicine used to treat diabetes. — Photo by Reneé Comet


It wasn’t until the hospital pharmacist talked to the man’s daughter that they found the explanation. The patient had begun taking a dietary supplement that included Saint John’s wort, which is marketed to improve mood. “No one had mentioned it because no one really thought of it as a medicine,” says Boullata. But Saint John’s wort can speed the breakdown of some prescription medicines by eliminating them from the body before they can take full effect. If the blood test hadn’t alerted doctors, the supplement might have triggered rejection of the kidney — or even death.

Today, half of all Americans take dietary supplements, according to the National Institutes of Health’s Office of Dietary Supplements. Consumers spend more than $28 billion a year on vitamins, minerals and herbal remedies, in hopes that they’ll cure everything from insomnia to depression. And because many dietary supplements are touted as “natural” and are often sold in health food stores, it’s easy to assume they’re harmless.

While supplements can be harmful at any age, men and women age 50 and older are more likely to encounter problems. First, older people more often have chronic conditions like kidney or liver disease, which make it harder for the body to process compounds found in supplements. Then, too, they usually take more prescription drugs than younger people — and the more medications you take, the greater the risk of hazardous interactions with supplements.

The Food and Drug Administration regulates dietary supplements but does not apply the same rules it uses for medications. Manufacturers are not required to obtain approval from the FDA before marketing supplements. Under federal law, manufacturers are responsible for making sure their supplements are safe, and the FDA steps in only when troubles arise. Unfortunately, adverse interactions with prescription drugs may go undetected for a long time, even by physicians.

Disturbing trend

According to recent survey by the AARP Public Policy Institute, 59 percent of people 50 and older had used supplements in the previous month, and 52 percent took them daily. Fewer than half said they talked to their doctors about the pills they took.

“It’s a serious problem, and getting more serious as the number of medications and herbal products increases,” says K. Simon Yeung, a pharmacist and herbalist at Memorial Sloan-Kettering Cancer Center, where he manages a database of supplement information available to physicians and patients. According to Yeung, about 50 percent of cancer patients use some kind of dietary supplement to ease symptoms or side effects — or, out of desperation, in search of a cure.

Yeung is convinced some herbs help alleviate their symptoms. Unfortunately, several popular herbal supplements pose risks for people with cancer. Saint John’s wort, the same herb that washes antirejection drugs out of the body, can also speed the breakdown of certain cancer chemotherapies, robbing them of cancer-killing potency. And vitamin C, in megadoses, can interfere with the effectiveness of cancer drugs.

Next: Have blood clots? Beware of garlic supplements. »

Even garlic can be risky

People taking medications to prevent blood clots are vulnerable to dangerous interactions with supplements. Garlic may seem harmless, for example, but at the high doses found in supplements, garlic acts as a blood thinner. If you’re on a prescription drug to prevent blood clots, garlic supplements may make your blood too thin, increasing the risk of excessive bleeding. Ginseng, green tea supplements and vitamin K supplements can reduce the effectiveness of certain blood-thinning drugs as well.

Also at risk are patients taking drugs for depression or other psychiatric problems. Ginkgo and ginseng have both been linked to adverse interactions with psychiatric medications. Dietary supplements with psyllium, which is used as a laxative, can cause problems by reducing absorption of prescription medications, including carbamazepine and lithium, which are widely used to treat psychiatric symptoms.

The extent of the danger isn’t clear in part because so little is known about many of the active ingredients in supplements. The fact that ingredients in herbal combinations vary from batch to batch only complicates the problem. “There are 5,300 distinct dietary supplements, and very few of them have been studied systematically,” says Vanessa Grubbs, M.D., an expert in kidney disease at San Francisco General Hospital.

Grubbs began to be concerned about supplements when many of the patients coming to see her because their conditions had worsened told her they were taking them. Looking at a national health survey, Grubbs and her colleagues found that 6.5 percent of kidney patients were taking a supplement that contained one or more of 39 herbs considered to be dangerous for people with kidney problems, including nettle and sassafras.

Further, few dietary supplements have been tested to see how they interact with prescription drugs, so no one really knows which combinations are likely to cause trouble. “Pharmacologists can predict some potential interactions based on what we know about the biochemistry involved,” says Boullata. “But often we only discover there’s a problem when something bad happens.” A patient, he says, “has what looks like a heart attack or sudden unexpected changes in liver or kidney function. Eventually we discover that the cause isn’t their disease or their prescription medication but a dietary supplement they’re taking.”

And there are other hazards, such as contamination. In 2009, the FDA fingered 72 weight-loss products that contained ingredients not listed on their labels, such as traces of lead and arsenic.

Still, experts emphasize that some dietary supplements can be helpful. “Most dietary supplements are generally safe for most people at the recommended levels,” says Paul Coates, director of NIH’s Office of Dietary Supplements. He points out that supplements like calcium or vitamin B12 may be especially beneficial to people over 50 who have difficulty getting all the nutrients they need in foods.

The National Center for Complementary and Alternative Medicine also has useful information online about many commonly used dietary supplements. But the best place to start is with your doctor and pharmacist. Make sure they know if you’re taking a dietary supplement of any kind, including a multivitamin. And before you start taking any new supplement, no matter how “natural” or harmless it may seem, talk to your doctor or pharmacist.

http://www.aarp.org/health/drugs-supplements/info-04-2012/supplements-interfere-with-prescription-drugs.html

Two health care "stocks under rocks"

FORBES

Investing

4/17/2012 @ 4:58PM

Two health care "stocks under rocks"

The first is Cyberonics Inc. CYBX/NASDAQ), a Houston-based company that makes a medical device for the treatment of epilepsy. The tiny device, implanted in the shoulder of patients, delivers a pulse of electricity to the brain, and it’s been found to be remarkably effective for the treatment of refractory epilepsy. Patients need to exhaust other treatment methods first, but when they do the device is fully covered by insurance. Cyberonics is profitable based solely on its current U.S. business, so as the company continues to expand its international presence, I think earnings will improve.

Another upside for Cyberonics is in an entirely different line of business: depression. Research has shown that the device also produces positive results for patients with treatment-resistant forms of depression. The FDA approved the device for the treatment of depression in 2005, but when it comes to medical devices and treatments, the question isn’t just, “Does it work?” It’s “Will insurance pay for it?”

Fortunately, there’s reason to believe reimbursement for the use of the device to treat at least some forms of depression is possible, and if that happens, Cyberonics will be staring at a potential market that could far exceed the size of the epilepsy market. Cyberonics has also made an investment in Imthera Inc., a company developing a device for the treatment of sleep apnea, and when you add to that the fact that the company is also researching the use of the device to treat chronic heart failure, you have the makings of what could be a really terrific story.

The company is run by some very smart people, and at $37 a share, it appears attractively priced. Our analysts with Burkenroad Reports have a target price of $40. This growth stock sells at about 32 times our expected earnings for 2012 and represents an interesting investment based solely on the epilepsy market. If reimbursement is approved for the device’s use in the treatment of depression, it could really attract Wall Street’s attention.

http://www.forbes.com/sites/peterricchiuti/2012/04/17/two-health-care-stocks-under-rocks/

From Medscape Medical News > Psychiatry

Positive Results for Deep TMS in Major Depression

Caroline Cassels

Authors and Disclosures

April 18, 2012 — Results from a double-blind, multicenter, controlled trial show that deep transcranial magnetic stimulation (TMS) is safe and effective in patients with major depression.

After 5 weeks of treatment, 30.4% of patients in the active treatment group achieved remission from depression, which was defined as a Hamilton Depression Rating Scale (HDRS-21) score of less than 10. In comparison, 14.5% of the sham treatment control group achieved remission (P = .0148), according to information released by Brainsway Ltd, developers of the device used in the study.

Further, the company reports there was a significant response to treatment, defined as a greater than 50% decrease from baseline HDRS-21 scores, in 36.7% of patients in the active treatment group vs 20.5% in the control group (P = .0148).

On the basis of a US Food and Drug Administration (FDA) approved clinical trial protocol, the study included 233 patients at 14 medical centers in the United States, 4 in Israel, 2 in Germany, and 1 in Canada.

All trial participants suffered from major depression and had previously failed to respond to therapeutic treatments or could not tolerate antidepressant medication owing to side effects.

Brainsway says it expects the study results will support its application for FDA approval to market its deep TMS system for the treatment of major depression in the United States.

http://www.medscape.com/viewarticle/762249

Brainsway in breakthrough for depression treatment

The company reports that treatment with Deep TMS was found to be effective and safe, with no side effects.

17 April 12 11:54, Globes' correspondent

 

Brainsway Ltd. (TASE:BRIN) today announced good results of its multicenter trial of its Deep TMS (transcranial magnetic stimulation) device for the treatment of severe depression. The treatment was found to be effective and safe, with no side effects.

 The trial included 233 patients at four medical centers in Israel, fourteen in the US, one in Canada, and two in Germany. The patients in the trial had previously failed to respond to therapeutic treatments, or suffered from side effects of those treatments.

After five weeks of treatment, there was a statistically significant difference between the patients treated with Deep TMS and the control group, based on the Hamilton Depression Rating Scale: 30.4% of the patients treated with Deep TMS achieved remission, compared with 14.5% of the control group.

The final results of the trial will be received when the database is closed and full statistical analysis of the results is completed.

Brainsway CEO Uzi Sofer said, "We will make a presentation about the results to investors in a few days. We will submit an application to the US Food and Drug Administration (FDA) for this indication by the end the second quarter of 2012."

Since 2008, the FDA has approved use of Deep TMS up to a depth of 1.5-2 centimeters into the brain tissue, although the device can penetrate up to 6-7 centimeters to the parts of the brain that are the source of depression and addiction.

Brainsway has CE Mark for use of Deep TMS for the treatment of depression, manic-depression, and post traumatic stress syndrome. The company expects to begin marketing the device in Latin America this year. A few months ago, it obtained Israel Ministry of Health approval for use of the device for the treatment of depression, manic-depression, and schizophrenia.

Brainsway's share price rose 38.2% by midday to NIS 27.80, giving a market cap of NIS 320 million.

http://www.globes.co.il/serveen/globes/docview.asp?did=1000741747

Vanderbilt To Study Deep Brain Stimulation For Depression

Vanderbilt To Study Deep Brain Stimulation For Depression

Released:4/16/2012 3:00 PM EDT
Source:Vanderbilt University Medical Center

Newswise — Vanderbilt University Medical Center is one of approximately 20 centers in a nationwide clinical study investigating the use of deep brain stimulation (DBS) as an intervention for patients with major depression.

BROADEN™ (BROdmann Area 25 DEep brain Neuromodulation) is the first randomized clinical research study to investigate DBS as an intervention for patients diagnosed with unipolar major depressive disorder (excluding bipolar disorder) who have not improved after multiple treatments.

DBS is a therapy that uses mild pulses of current (stimulation) to regulate specific areas of the brain, much like a pacemaker uses pulses of current to regulate the heart.

In this study, stimulation is being delivered to an area of the brain known as Brodmann Area 25, which is believed to function differently in people with major depression and appears to be overactive when people are profoundly sad and depressed.

Vanderbilt was chosen to participate in this study, which builds on the work of a research team from the University of Toronto led by Helen S. Mayberg and Andres Lozano, because of its extensive experience with various forms of neuromodulation and in treating psychiatric illness.

Ronald Salomon, M.D., associate professor of Psychiatry, is the principal investigator for the study at Vanderbilt, working with Joseph Neimat, M.D., assistant professor of Neurological Surgery, the co-investigator and neurosurgeon responsible for performing the DBS implantation procedure.

Patients enrolling in the study must be willing to transfer psychiatric care to Dr. Salomon during the course of the 14-month study.

Once the study has been completed, patients will have the option to either participate in a long-term follow-up study, return to the care of their referral psychiatrist while maintaining DBS programming-related care with a BROADEN study center, or have the DBS system removed.

The study sponsor is providing the investigational study device and study-related care at no charge to enrolled patients.

Participants must be between 21 and 70 years old, with the onset of the first episode before age 45, and currently be diagnosed with major depressive disorder.

Other criteria include being depressed for at least one year in their current episode, having tried at least four treatments in their current episode, and having tried a course of psychotherapy for depression at least once.

Participants cannot have met criteria for borderline or antisocial personality disorder in the last 12 months, cannot have GAD (Generalized Anxiety Disorder) as a primary diagnosis during the current episode, cannot have co-morbid OCD (Obsessive-Compulsive Disorder), PTSD (Post-traumatic Stress Disorder), panic disorder, or eating disorder (unless in remission for 6 months), and cannot have been diagnosed with schizophrenia, schizoaffective disorder, or other lifetime psychotic disorders.

The BROADEN study is sponsored by St. Jude Medical and is being conducted under a U.S. Food and Drug Administration (FDA) investigational device exemption (IDE). BROADEN is a trademark of Advanced Neuromodulation Systems doing business as St. Jude Medical Neuromodulation Division.

For more information about the study, please call toll-free 877-796-8732 or visit www.BroadenStudy.com.

http://www.newswise.com/articles/vanderbilt-to-study-deep-brain-stimulation-for-depression

PROFESSION End-of-life care: Pain control carries risk of being called a killer Accusations of euthanasia are common as patients, families and even other health professionals struggle to adjust to the new realities of end-of-life care. By Kevin B. O'Reilly, amednews staff. Posted April 16, 2012. Three decades after hospice emerged as the standard of care for terminally ill patients, the end-of-life treatments that palliative medicine physicians provide are frequently referred to as murder, euthanasia and killing. More than half of hospice and palliative medicine physicians say patients, family members and even other health professionals have used those terms to describe care they recommended or implemented within the last five years, according to a nationwide survey of 663 palliative care doctors in the March Journal of Palliative Medicine. Who’s calling palliative care “euthanasia” Links See related content Common palliative care treatments such as the use of opiates, sedatives and barbiturates to control pain and other symptoms are enough to draw accusations of murder and euthanasia, the study said. The troubling survey results come nearly six years after the American Board of Medical Specialties approved the hospice and palliative medicine subspecialty certification, and 30 years after the creation of the Medicare hospice benefit. Nearly 1.6 million Americans received hospice care in 2010, up from about 25,000 in 1982, said the National Hospice and Palliative Care Organization. And palliative medicine has made its presence felt in hospitals, with 85% of 300-plus bed hospitals boasting palliative care teams, according to the New York City-based Center to Advance Palliative Care. Yet the growing use of hospice and palliative care is creating more opportunities for misunderstandings, experts said. New developments in end-of-life care — aggressive pain and symptom management (even to the point of unconsciousness), along with a greater willingness to withdraw advanced, life-sustaining treatments such as mechanical ventilation, dialysis, and artificial hydration and nutrition — still strike many people as wrong. The survey’s findings highlight the gap between the well-established ethical and legal boundaries that demarcate acceptable end-of-life care and the understanding of patients, families and other members of the health care team, experts said. Nearly 1.6 million Americans received hospice care in 2010, up from about 25,000 in 1982. “It’s alarming,” said H. Rex Greene, MD, a practicing oncologist and palliative medicine specialist in Lima, Ohio. “To accuse legitimate palliative care physicians of euthanasia and murder is a horrible mischaracterization of what’s done to relieve symptoms at the end of life.” Twenty-five of the physicians surveyed said they were formally investigated by their institutions, state medical boards or prosecutors, with about half of those cases related to the use of opiates to manage dying patients’ pain. Nearly a quarter of the investigations were related to the use of palliative and sedative medications when discontinuing mechanical ventilation. An additional 8% of the investigations were for palliative sedation — the practice of sedating to unconsciousness terminally ill patients who have severe, refractory pain. All of these treatments — when conducted with the consent of patients or surrogate decision-makers and implemented with the intent of alleviating pain or other symptoms in terminally ill patients — are broadly accepted as ethically and legally appropriate, even if they have the secondary effect of speeding the dying process. “Physicians have an obligation to relieve pain and suffering and to promote the dignity and autonomy of dying patients in their care,” says the American Medical Association Code of Medical Ethics. “This includes providing effective palliative treatment even though it may foreseeably hasten death.” Hard-wired misperceptions Although none of the physicians investigated was found at fault, most reported worry, anger, anxiety, isolation, depression and difficulty working as a result of the ordeal. Euthanasia accusations — whether voiced in the patient’s room or in the courtroom — could have a chilling effect on physicians’ treatment of dying patients’ symptoms, said John G. Carney, CEO of the Center for Practical Bioethics, a Kansas City, Mo., think tank that works to improve end-of-life care. “I’m deeply concerned that if we don’t pay attention to the message in this article, we are going to be dealing with this issue of physicians who are reluctant to do what they know to be right because they are afraid of what people will say or that someone’s going to investigate,” said Carney, a former hospice executive director. The distinction between aggressive pain control or the withdrawal of life-sustaining treatments and euthanasia is still lost on many patients and families, physicians said. “These misperceptions are really pretty hard-wired and difficult to eliminate,” said David Casarett, MD, chief medical officer of the University of Pennsylvania Health System’s hospice program in the Philadelphia area. “Believe me, if there were an easy way to communicate these issues, then we wouldn’t have highly qualified physicians called before medical boards to explain their actions. To some degree, this is a cultural change. We’re far ahead of where we used to be 20 years ago. On the other hand, we can’t wait another 20 years for these things to go away.” Transformation in end-of-life care Doctors who care care for dying patients should take into account the public’s lagging understanding of end-of-life treatments, take time to explain their intricacies and make use of ethics consultation services, said Porter Storey, MD, executive vice president of the American Academy of Hospice and Palliative Medicine. “When I started training in this area 30 years ago, it was a rare thing to remove a feeding tube because nobody lived long enough to get that sick,” said Dr. Storey, who practices outpatient palliative care in Boulder, Colo. “Now many people are living until they are extremely debilitated on life support. And if you work in an ICU, you want to sit down and take time and talk to people, but when it’s happening every day, it’s hard to remember sometimes that the public didn’t get informed that things have changed.” Yet confusion about end-of-life care is not limited to patients and families. A majority of the doctors surveyed said that other physicians or health professionals at times characterized their palliative care treatments as murder, euthanasia or killing. As end-of-life care has become more specialized, the gap between what palliative care specialists see as appropriate care and other doctors’ perception of those treatments has grown, physicians said. “Those of us in palliative care and hospice don’t think that much about putting a patient on a large dose of an opioid like morphine. We do it all the time, and we see patients do well,” said Dr. Casarett, associate professor of medicine at the Perelman School of Medicine at the University of Pennsylvania. Recently, a patient dying of cancer enrolled in Dr. Casarett’s hospice program after deciding to stop chemotherapy treatment. The oncologist caring for the patient was upset and talked with Dr. Casarett, saying that the combination of stopping curative treatment and using high doses of opiates was wrong. “He said, ‘We might as well just be walking away, and we might as well just shoot [the patient] now,’” Dr. Casarett recalled. “It still stings to hear that,” he said. But Dr. Casarett takes solace in knowing that he is doing right by his patients. “I tell other physicians that this is the standard of care, and that these sorts of medications and interventions are safe and effective.” Back to top ADDITIONAL INFORMATION: Who’s calling palliative care “euthanasia” More than half of palliative care doctors have been told the care they recommended or provided is “murder,” “euthanasia” or “killing.” The frequency of such accusations varies by source and at times includes other doctors. Patient: 25% Patient’s friend or relative: 59% Physician’s friend or relative: 25% Another physician: 56% Another health professional: 57% Source: “Prevalence of Formal Accusations of Murder and Euthanasia against Physicians,” Journal of Palliative Medicine, March (ncbi.nlm.nih.gov/pubmed/22401355/) Back to top Weblink “Prevalence of Formal Accusations of Murder and Euthanasia against Physicians,” Journal of Palliative Medicine, March (www.ncbi.nlm.nih.gov/pubmed/22401355/) “Opinion 2.201 — Sedation to Unconsciousness in End-of-Life Care,” American Medical Association Code of Medical Ethics, adopted June 2008 (www.ama-assn.org/ama/pub/physician-resources/medical-ethics/code-medical-ethics/opinion2201.page)

http://www.ama-assn.org/amednews/2012/04/16/prl20416.htm

Treating depression with electrodes inside the brain

By Dr. Sanjay Gupta and Andy Segal, CNN

updated 1:16 PM EDT, Sat April 14, 2012

Inside the 'battery-powered' brain

STORY HIGHLIGHTS

• For 40 years, Edi Guyton suffered from debilitating depression
• She volunteered to have electrodes implanted into her brain
• Dr. Helen Mayberg pioneered research to use "deep brain stimulation" on depression
• She is now hoping for FDA approval for the method

Editor's note: "Battery-powered brain," a report by CNN's chief medical correspondent Dr. Sanjay Gupta, premieres on CNN Presents, Sunday, April 15, at 8 p.m. ET. Gupta is also an assistant professor of neurosurgery at Emory University's School of Medicine.

Atlanta (CNN) -- The first time Edi Guyton tried to commit suicide, she was 19 years old, wracked with depression and unable to deal with the social and academic pressure of college.

Even as a little girl, Guyton never seemed happy. Her mother had encouraged her to smile, but she didn't see any reason to. In her mind, everyone who smiled was "faking it."

She often thought about taking her own life, and one night in her college dorm, Guyton's dark thoughts gave way to action. With a razor blade, Guyton cut one wrist, then the other.

"I think I wanted it to get better or I wanted to die," she said. "The point was that everything was so bad, I wanted people to know that it was controlling me."

 

Edi Guyton lived with debilitating depression for 40 years before experimental brain surgery.

Her depression controlled her life for the next 40 years -- until she decided to volunteer for an experimental treatment. A neurosurgeon would drill two holes in Guyton's skull and implant a pair of battery-powered electrodes deep inside her brain.

The procedure -- called deep brain stimulation, or DBS -- targets a small brain structure known as Area 25, the "ringleader" for the brain circuits that control our moods, according to neurologist Dr. Helen Mayberg.

Mayberg's groundbreaking research on this part of the brain showed that Area 25 is relatively overactive in depressed patients. So, Mayberg hypothesized that in patients who do not improve with other treatments, Area 25 was somehow stuck in overdrive.

Mayberg published the results of her brain scan studies in 1999, the same year Edi Guyton attempted suicide again -- this time an overdose of prescription meds that were supposed to ease her depression.

"It's not that you won't be happy or that you aren't happy; it's that you can't be happy," Guyton said.

The first patients

Four years after publishing her research, Mayberg was ready to try what had never before been done: applying deep brain stimulation to Area 25.

 

Area 25 is the junction of all brain circuits that control our moods, according to neurologist Dr. Helen Mayberg.

 

DBS had been used since 1997 as a treatment for movement disorders, including essential tremor, Parkinson's disease and dystonia. Mayberg theorized the low voltage current from DBS could also help severely depressed patients.

Her first surgical experiment in 2003, in collaboration with neurosurgeon Dr. Andres Lozano at Toronto Western Hospital in Canada, was more about testing for safety than actually treating the patients.

"For all we knew, we were going to activate [the circuits] and actually make people feel worse," Mayberg explained.

The six patients who volunteered for the procedure had all tried and failed conventional treatments. Some had attempted or considered suicide.

"We had patients who were profoundly without any options and suffering," she said.

All six were lightly sedated when the holes were drilled and the electrodes implanted, but they were awake to describe what they experienced. Several patients reported profound changes just minutes after the stimulator was turned on. One said the room suddenly seemed brighter and colors were more intense. Another described heightened feelings of connectedness and a disappearance of the void.

The patients' descriptions during the procedure went far beyond anything the doctors expected.

One patient spontaneously talked about the first crocus blooms in early spring. Mayberg wondered if the procedure had triggered a hallucination or perhaps the electrode had touched a memory circuit. The patient explained it's the feeling of looking forward to something new and rejuvenating

Mayberg says she struggled to remain a dispassionate scientist, but her empathy for the desperate patients who were, in effect, collaborators in the experiment got the best of her.

"I did a lot of crying," she said.

After six months of stimulation, four of the six the patients were significantly better. Mayberg has since reported similar results for 31 other patients.

Mayberg and Lozano published the results of that first DBS experiment in 2005, the same year Edi Guyton's depression subverted her career.

'I felt nothing'

For years, Guyton had thought she could outrun her despair by working hard. She had earned her Ph.D. while raising two daughters, landing a tenured position as a professor, earning accolades and awards for her teaching and research, and ultimately becoming chair of Georgia State University's early childhood education department. She said she got there by "faking it."

"I was the great pretender," Guyton said.

Then, after 22 years working at GSU, she told her boss and colleagues about her struggle with depression and retired from the job she loved. Still not fully grasping the nature of her illness, she blamed herself.

"After all, what do I have to be depressed about?" she thought.

She tried a variety of treatments, including talk therapy and psychiatric medicines, but nothing worked.

For the next several years, nine sessions of electroconvulsive therapy kept her stable. "I didn't like it, but it worked," she said. "But then I went back down. And I went back down very deep."

With the support of her husband, Guyton managed to stay in the fight. She inquired about the experimental DBS procedure being offered by Dr. Helen Mayberg and her colleague, psychiatrist Paul Holtzheimer, at Emory University in Atlanta.

Mayberg remembers the first time she saw Edi Guyton. Her slow movements were "like being in a muck," an obvious sign of severe depression, she said. "You could pick her out of a line up."

Seventeen patients out of more than 1,000 who had inquired were ultimately selected for the experiment. Ten of them, including Guyton, had major depressive disorder and the seven others had depression as a result of bipolar disorder.

The doctors warned them all that the procedure carried the risks of any other brain surgery, including brain damage and death, and no guarantee the depression would lift. Guyton signed the consent form, feeling that she had little to lose.

"It was that bad," she said.

She could not even bond with her family. The most vivid example was visiting her baby grand-niece. Guyton could barely go through the motions.

"Somebody handed her to me and I held her, but I didn't even put her face to mine," Guyton said. "I just held her because I thought, 'This is what a great-aunt does. She holds the child. She admires the child. And then, thank God, she gives the child back.' And I felt nothing. Nothing."

A new lease on life

On February 23, 2007, Guyton rolled into a surgical suite, propelled by a sweet and sour mixture of hope and hopelessness. Her head was mounted in a rigid frame as the doctors studied computer-enhanced images of her brain.

Dr. Robert Gross, the neurosurgeon, began drilling the holes in her skull.

Edi clenched her teeth. "The tears came," she says. "The sound of the drill, the feeling of it: Not painful, just like somebody's touching you. That was, I think, what kind of woke me up and said this is your brain that is being drilled into. Somebody is going into your brain."

The two holes allowed Gross to insert hollow tubes called cannulas, which created a pathway for the DBS electrodes -- one on each side of the brain. The electrodes are 1.27 millimeters in diameter, "about the thickness of angel hair pasta," Gross explained.

As they position the electrodes, the doctors are able to monitor the sound of neurons firing. The gray matter makes a raspy sound. The white matter is silent. And that's where the sweet spot seems to be: the white matter slightly below Area 25.

Each electrode has four contacts. Each contact can be independently controlled, on or off, with various levels of electricity. Typically, the doctors apply about a thousandth of the power that's used in a flashlight bulb. At the target, it stimulates approximately 1 cubic centimeter of brain tissue, "about the size of a pea," according to Gross.

Finding which contact works best is done through trial and error as the patient describes what feels best. As a benchmark, the doctors asked Guyton to rate her feelings of dread on a scale of 1 to 10.

"Eight," she reported.

Two minutes later, with contact No. 1 on, Guyton said, "Three."

But doctors would get an ever better result with contact No. 2.

Shortly after the second contact was turned on, Guyton quietly announced, "I almost smiled." Then she chuckled.

Dr. Holtzheimer asked, "Did something strike you as funny? Or was it just sort of spontaneous?"

"I was thinking about playing with [grand-niece] Susan," Guyton replied. "That was when I almost smiled. But when I laughed, that was because I almost smiled."

She had imagined holding the child and looking into her face. "I felt feelings that I thought were gone," she would later say.

How did it feel to have a machine and electricity transform her emotions?

"It felt fantastic," she said. "I didn't care what was doing it!"

To determine whether the surgery was truly effective or if the patients felt better simply because they believed in the treatment, the doctors told the patients that some of the battery packs powering the electrodes inside their brains would be turned off, while others would be left on, to measure any placebo effect.

Guyton's power pack was turned off, and her depression quickly returned. With the stimulator back on, she improved.

Based on her scores in February from a widely used psychological test called the Hamilton Rating Scale for Depression, Guyton's mental illness is in remission. Her ups and downs are the same that any healthy person would experience -- as long as the battery in the stimulator implanted under her collarbone remains charged.

Five years after the surgery, Edi Guyton is one of Mayberg's most dramatic success stories. She volunteers with a mental health advocacy group, she's active with a church and she's in a writer's club. And last fall she toured Italy with college friends who knew her from the days she had put a razor to her wrists.

To be sure, Guyton still has some bad days. "I don't feel good all the time," she admitted, and she sometimes worries that a bad spell could be lurking on the horizon. "But this gives me the capacity that if I can, if there is joy in my life, I have the capacity to feel it."

Next steps

As much as Mayberg's experiments showcase how far brain science has advanced, there is still much more to learn. In fact, more than 10 years after her pioneering studies on Area 25, Mayberg is still trying to answer basic questions about the experimental treatment she conceived. Does the electricity from DBS activate neurons near Area 25 or inhibit them? Is DBS flipping a switch or knocking down a wall?

"To be brutally honest, we have no idea how this works," Mayberg said.

If there is joy in my life, I have the capacity to feel it.

Edi Guyton, patient Mayberg is the co-holder of a patent for the procedure, which has been licensed to St. Jude Medical, Inc., a company that manufactures and sells DBS equipment. St. Jude is hoping to win Food and Drug Administration approval for commercial use of DBS for treatment-resistant depression.

 

The FDA awarded limited approval in 2009 to Medtronic, Inc., to use DBS on a different part of the brain for intractable obsessive compulsive disorder. Medtronic is funding a study to determine if that part of the brain, the ventral capsule/ventral striatum, could also be a viable target for depression.

In the meantime, Mayberg still hopes to answer why DBS helps some patients but not others. After all, if Area 25 is the "ringleader," why doesn't everyone improve? Mayberg simply does not know.

"We've got to understand the biology better," she says. "So until we're actually hitting 90% or really effectively helping everybody, we've got our work cut out for us."

http://www.cnn.com/2012/04/14/health/battery-powered-brain/index.html

Magnetic pulses draw good reviews from doctors treating depression

Therapy shows positive results for those getting treatment

Nan Miller, 61, of El Paso, Ill., undergoes a transcranial magnetic stimulator maintenance treatment at Loyola University Chicago Stritch School of Medicine in Maywood. TMS sends short pulses of magnetic fields to the brain for the treatment of major depression. (Chuck Berman, Chicago Tribune / February 16, 2012)

 

By Janice Neumann, Special to the Tribune

April 11, 2012

When the darkness lifted in Nan Miller's mind, she realized the new therapy for her depression was finally working.

Transcranial magnetic therapy, which was approved by the FDA for use with the NeuroStar TMS therapy system in 2008, has been a lifeline to scores of other patients, who could not shake their depression despite multiple rounds of antidepressants, anti-anxiety medications or even electroconvulsive therapy.

In the therapy, a device delivers small electric pulses to nerve cells in the emotional regulation centers of the brain through a wire coil wrapped around the patient's head. The patient sits relaxing in a comfortable chair for the roughly 37-minute treatment, which is repeated for 20-30 sessions over four to six weeks. Side effects include tingling of the scalp and headache.

Miller, 61, had tried about 10 antidepressants over the years and although some helped, she continued to feel terrible. She also tried ECT but did not want to repeat that treatment because it requires sedation, induces seizures and can cause some memory loss. But with thoughts of suicide, she knew she needed help.

After only a few weeks of therapy, she felt better. Her husband has noticed the difference too.
"He was seeing things I didn't notice, that I was laughing, telling jokes — which before I had done in my head, but you just don't have the energy for them to come out of your mouth (when depressed)," said Miller, a retired teacher who lives in El Paso, Ill.

Dr. Murali Rao, who chairs the department of psychiatry and behavioral neurosciences at Loyola University Stritch School of Medicine, has been impressed with the results, noting some depression can be hard to treat. He has treated about 25 patients, including Miller, and found two-thirds improved, with a third of those "totally recovered."

"The problem is because it's a new modality, it's still not available to most people who can use it," said Rao. "Once it becomes available, if we introduce it early in treatment, we'll probably see more response," said Rao, who is recruiting patients for a study on TMS use in individuals suffering from clinical depression and chronic tinnitus, or ringing in the ears.

Not all insurers will cover TMS and a full regimen can cost about $12,000. Only a handful of Chicago institutions and doctors offer TMS, including Northwestern Medical Faculty Foundation and Rush University Medical Center.

Dr. Carl Wahlstrom Jr., a Chicago psychiatrist who began offering TMS in 2009, has seen about 80 percent of the 45 patients he has treated improve. Wahlstrom noted TMS works on the electrical signaling of the brain and medication on chemical signals, so the two "seem to have a combined effect that's more powerful than either treatment alone."

"I've been really pleased with some people who were really ill and tried so many things, including ECT, and came here and got a positive treatment response," said Wahlstrom, who is also an assistant professor of psychiatry at Rush University Medical Center.

Wahlstrom also noted patients tend to tolerate TMS better than other treatments so will continue with a full regimen.

Doreen, one of Wahlstrom's patients, had been hospitalized for depression and anxiety and was considering ECT. But before relocating to Chicago from California, her former psychiatrist suggested TMS instead. She has completed a round of treatment.

"I'm feeling pretty good so far," said Doreen, who asked that her last name not be used. "I was in a pretty bad place."

The handful of patients receiving TMS through Alexian Brothers Behavioral Health Hospital have mostly improved, according to Dr. Greg Teas, psychiatrist and medical director of the hospital. Teas said the treatment could be good for the 10 percent of patients who have trouble tolerating medication or women who are pregnant and prefer to forgo drugs that could potentially harm an unborn child. Teas said more data was needed to determine how much maintenance treatment might be needed to sustain an improved mood.

"It's going to be primarily looked at by consumers as safe and well tolerated treatment, as well as something that offers them hope of improving their condition," said Teas.

While Dr. Lawrence Robbins, a Northbrook-based neurologist, has seen about 30 percent of his 35 patients improve through TMS, he said individuals who had suffered depression for years could be harder to treat. Robbins hopes to eventually use the treatment for migraine patients.

"The brain with depression kindles itself like kindling logs on a fire, so the more you have, the more likely in a year or two years you will be depressed," said Robbins.

"The bottom line is we need better treatments for depression," said Robbins.

http://www.chicagotribune.com/health/ct-x-0411-transcranial-therapy-20120411,0,6233965.story

Implanted device proves life-changing for Coralville woman

7:37 PM, Apr. 9, 2012

Meghan D’Souza-Ewinger, a library assistant at the Coralville Public Library, returns a book to the shelf last week. Five years ago, doctors implanted a device in D’Souza-Ewinger’s left shoulder area and neck to control her partial seizures. / Josh O’Leary / Iowa City Press-Citizen

Written by

Josh O’Leary

Iowa City Press-Citizen

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Meghan D’Souza-Ewinger, a library assistant at the Coralville Public Library, checks out materials last week. Five years ago, doctors implanted a device in D’Souza-Ewinger’s left shoulder area and neck to control her partial seizures. / Josh O’Leary / Iowa City Press-Citizen

 

Meghan D’Souza-Ewinger remembers those days she was so sick that even a trip to the grocery store was agonizing.

The sound of the rolling carts, the repetition of the passing food labels, the fluorescent lighting — it was all too much. She would flee the store for the calm of the car.

“I just felt very trapped and scared and hopeless,” said D’Souza-Ewinger of that period eight years ago when she was diagnosed with epilepsy while an undergraduate at the University of Iowa.

Today, remarkably, that feeling of despair is behind her. The 29-year-old Coralville woman has passed the five-year milestone since doctors implanted a device in her neck, often referred to as a pacemaker for the brain, that proved to be life changing.

“I was basically bedridden for a long time,” D’Souza-Ewinger said. “Now I have two jobs, I’m healthy, I like to do a lot of volunteer work and I’m really social. I kind of forget how it used to be, unless I’m forced to think about it.”

The spells first came on in force during her junior year at UI, where the Burlington native was studying communications. The Vertigo, nausea and a feeling of what she describes detachment from her own body — jamais vu — was debilitating. She moved home and began seeing doctors, at first suspecting an inner-ear problem because of the dizziness.

D’Souza-Ewinger was too sick to return to Iowa City the first semester of what was supposed to be her senior year. That fall, she passed out while talking with her mother in their home. Her ears rang, her vision faded, then she lost consciousness. When she awoke, her mother, a nurse, was calling for an ambulance.

Following the spell, and after nearly a half year of searching for answers, an EEG run by a neurologist revealed she had epilepsy and had suffered a complex partial seizure. Unlike the violent muscle contractions of a grand mal seizure, D’Souza-Ewinger had been experiencing complex and simple partial seizures, which can result in spontaneous sensory symptoms and altered consciousness.

In hindsight, there were other clues when she was younger, D’Souza-Ewinger said. The flashing lights at a school dance at age 11 triggered a spell that the family had thought was anxiety related. Another incident a few years later was chalked up to dehydration.

But now doctors had given a name to D’Souza-Ewinger’s condition, which had tied the self-described go-getter with big ambitions to her bed.

“I don’t really like to say I am an epileptic, because I feel that’s just one defining word,” she said. “But the scariest part was saying, ‘I have epilepsy and I always will.’”

Doctors would try a number of medications in the coming year, but side effects like stuttering and fogginess, as well as the overall ineffectiveness of the drugs, proved frustrating. Her first doctor built up hopes that a single medication would be all that was needed to kick the symptoms, she said, a second told her that she needed to accept her life as she now knew it.

“The four walls in my my bedroom were my life,” she said.

Even still, D’Souza-Ewinger managed to return to Iowa City in the spring, where she lived with her aunt and managed to finish her degree. When graduation day came in December 2004, she was too ill to attend.

Eventually, D’Souza-Ewinger and her mother’s persistence and determination to not give in brought them to a third doctor, Marc Hines, a neurologist who at the time was working out of Ottumwa. It was Hines who first brought up the idea of Vagus Nerve Stimulation, a technique that inhibits seizures by using an implant that pulses signals to the brain, which Hines said can often be overlooked by doctors as an option.

D’Souza-Ewinger underwent surgery in October 2006, just a few months after she married husband Kevin Ewinger. Doctors implanted the pacemaker-like device, which weighs less than an ounce and is about the size of a small pocket watch, near her left collarbone, then threaded a thin wire from the generator up the left side of her neck and coiled it around her left vagus nerve.

“The idea is that the stimulation goes retrograde, up to the brain,” said Hines, who now works at Covenant Medical Center in Waterloo. “The vagus nerve usually goes out to the body from the brain. It seems to enhance a network of inhibitory neurons, nerve cells, in the brain, that inhibit the seizures.”

D’Souza-Ewinger was allowed to heal from the surgery for a few weeks before Hines put the VNS device to work. Over the course of the next several months, the doctor incrementally ratcheted up the frequency and power of the pulse to find the most effective dosage. D’Souza-Ewinger felt better almost immediately, she said, and things only improved as the months passed.

More than 40,000 patients worldwide have been treated with VNS Therapy since it was introduced in the U.S. in 1997 as a means of reducing the frequency of seizures, according to Cyberonics, the Houston-based company that makes the devices. It has also been approved to treat depression.

“This is often very helpful, at the minimum, with reducing the medicines, and oftentimes with marked improvement in seizure control,” Hines said.

Last October, D’Souza-Ewinger went under the knife again, this time to change the battery in the device. Otherwise her trips to the doctor have been cut down to once every month or two.

“She’s a very unique person,” said her mother, Marlene Raid. “I don’t know that I could have gotten through this, but she did. So that strength inside of her is really powerful.”

D’Souza-Ewinger now has an active social life, and has a pair of jobs, including working as a library assistant at the Coralville Public Library. She devotes much of her free time to charity, with past projects including stitching dresses for underprivileged children and organizing small drives for the University of Iowa Children’s Hospital. She has made it a goal for 2012 to take part in at least one charitable event a month.

“For so many years I had felt trapped and closed in,” she said. “Now I feel so alive. I just want to do everything and really live. It’s incredible.”

http://www.press-citizen.com/article/20120410/NEWS01/304100074/Implanted-device-proves-life-changing-Coralville-woman

TMS Therapy: New Technology to Treat Depression

By: Melissa Stern

Updated: April 5, 2012

(Springfield, MO) -- A new discovery could mean good news for people who suffer from severe depression.

If your doctor has prescribed a number of antidepressants without results, TMS therapy could be an option.

Dr. H.J. Bains, a local doctor, usesTMS therapy -- a treatment that sends magnetic pulses into the brain -- on some of his patients. He says it's been around in Europe for 20-30 years, but the FDA approved TMS in 2008 in the U.S.

There are close to 350 clinics using it in the country, and Dr. Bains says his clinic is only the second in the state. He says TMS is one of the safest treatments he's seen and produces the fastest results.
"I haven't felt this good since I was a kid," says Lisa Nunn, a patient of Dr. Bains'. She says she has less anxiety and wants to do things besides lay in bed all day. "It's the best thing to happen to me in a long time."

Nunn says she had been on anti-depressants since she was 15, but nothing helped.

"It was quite bad. I slept a good deal of the time. Wasn't able to function well. I was in a pretty bad depression." She says after the first treatment she noticed a difference. "I had much more energy. I had much more stamina. I don't have the mood swings that I was having. I'm just generally a happier person."

Dwayne Dilbeck, her boyfriend, was very worried about her.

"She slept more of the day than she was awake," but he says he's noticed a huge difference. "She's more active. She's awake a lot more -- more alert. She's gotten back to where she's wanting to get back to writing again."

Dr. Bains says when patients first come in, he gives them a score on the depression scale.
"I have patients who come in with very high scores and by the time they finish treatment, their scores are almost close to zero to two or three, which is in the normal range."

He says TMS therapy sends an electrical pulse through the brain, and targets the area of the brain that controls mood.

"The area of the brain -- the prefrontal cortex -- that's the area of the brain which is underactive in people with depression."

The magnetic pulses recharge that area of the brain which helps take patients off their medications -- medications that could have side effects.

"You give medicine and you don't see any benefit for four to six weeks and all side effects from weight gains, sexual side effects, you name it."

But with TMS, Dr. Bains says results can be fast.

"I have seen patients who have shown improvement by the second or third week."

"The first week everything surprised me because she was more active," adds Dilbeck. "She felt like getting out and going shopping. Couldn't keep her out of the stores!"

"It seemed to me that I kind of woke up from a long sleep," adds Nunn.

At Dr. Bains' clinic, Bay Medical Consulting, TMS is $450 each session. He says it requires one treatment every day, five days a week, for six weeks. Each session is approximately 40 minutes long
You can experience mild tenderness on the head, but there are no other side effects. It is not covered by insurance.

It requires no anesthesia or medications, and the patient stays awake throughout the treatment.
Dr. Bains says it's also being used to help migraines, fibromyalgia, pain syndromes, hallucinations, and traumatic brain injuries.

Pregnant women who don't want to take medication can use it.

The American Psychiatric Association says it's good in some cases, but not effective for everyone.

Here is the APA's complete statement about TMS:
APA Practice Guidelines for Treatment of Major Depressive Disorder (MDD). Transcranial magnetic stimulation

Transcranial magnetic stimulation (TMS) uses a specifically designed magnetic coil that is placed in contact with the head to generate rapidly alternating magnetic-resonance-imaging-strength magnetic fields and produce electrical stimulation of superficial cortical neurons. Based on the results of a multisite randomized sham-controlled clinical trial of high-frequency TMS over the left dorsolateral prefrontal cortex (268), TMS was cleared by the FDA in 2008 for use in individuals with major depressive disorder who have not had a satisfactory response to at least one antidepressant trial in the current episode of illness. However, another large randomized sham-controlled trial of TMS added to antidepressant pharmacotherapy showed no significant benefit of left dorsolateral prefrontal cortex TMS (269). In comparisons of actual TMS versus sham TMS, most (270-272) but not all (273) recent meta-analyses have found relatively small to moderate benefits of TMS in terms of clinical response. Although the primary studies used in these meta-analyses are highly overlapping and the variability in TMS stimulus parameters and treatment paradigms complicates the interpretation of research findings, these meta-analyses also support the use of high-frequency TMS over the left dorsolateral prefrontal cortex. Lesser degrees of treatment resistance may be associated with a better acute response to TMS (274).

In comparison with ECT, TMS has been found in randomized studies to be either less effective than ECT (275) or comparable in efficacy to ECT (276-278), but in the latter studies TMS was more effective and ECT was less effective than is typically seen in clinical trials. A fewer number of studies have compared cognitive effects of TMS and ECT. One randomized trial found no significant difference between TMS and non-dominant unilateral ECT on performance on neuropsychological tests at 2 and at 4 weeks of treatment (276), although a small open-label trial reported a greater degree of memory difficulties with ECT than with TMS shortly after the treatment course (279).
Across all studies, TMS was well tolerated and was associated with low rates of treatment dropout (270, 280). Transient scalp discomfort and headaches were the most commonly reported side effects (280).

In clinical practice, the need for daily TMS could produce logistical barriers for some patients.
http://ozarksfirst.com/fulltext?nxd_id=627772