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Thursday, January 31, 2019

Transcranial magnetic stimulation (TMS): Hope for stubborn depression

Have you ever topped off your glass of cabernet or pinot noir while saying, “Hey, it’s good for my heart, right?” This widely held impression dates back to a catchphrase coined in the late 1980s: the French Paradox.

The French Paradox refers to the notion that drinking wine may explain the relatively low rates of heart disease among the French, despite their fondness for cheese and other rich, fatty foods. This theory helped spur the discovery of a host of beneficial plant compounds known as polyphenols. Found in red and purple grape skins (as well as many other fruits, vegetables, and nuts), polyphenols theoretically explain wine’s heart-protecting properties. Another argument stems from the fact that the Mediterranean diet, an eating pattern shown to ward off heart attacks and strokes, features red wine.

However, the evidence that drinking red wine in particular (or alcohol in general, for that matter) can help you avoid heart disease is pretty weak, says Dr. Kenneth Mukamal, an internist at Harvard-affiliated Beth Israel Deaconess Medical Center. All of the research showing that people who drink moderate amounts of alcohol have lower rates of heart disease is observational. Such studies can’t prove cause and effect, only associations.

Moderate drinking — defined as one drink per day for healthy women and two drinks per day for healthy men — is widely considered safe. But to date, the health effects of alcohol have never been tested in a long-term, randomized trial.
Grape expectations

Although some studies suggest wine is better for the heart than beer or hard liquor, others do not, according to a review article about wine and cardiovascular health in the Oct. 10, 2017, issue of Circulation. That’s not surprising, says Dr. Mukamal. “In many cases, it’s difficult to tease out the effect of drinking patterns from specific types of alcoholic beverages,” he explains. For example, people who drink wine are more likely do so as part of a healthy pattern, such as drinking a glass or two with a nice meal. Those habits — rather than their choice of alcohol —may explain their heart health.

Also, the French Paradox may not be so paradoxical after all. Many experts now believe that factors other than wine may account for the observation, such as lifestyle and dietary differences, as well as earlier underreporting of heart disease deaths by French doctors. What’s more, Dr. Mukamal notes, heart disease rates in Japan are lower than in France, yet the Japanese drink a lot of beer and clear spirits, but hardly any red wine.
Resveratrol reservations

What about the polyphenols in red wine, which include resveratrol, a compound that’s heavily advertised as a heart-protecting and anti-aging supplement? Research in mice is compelling, says Dr. Mukamal. But there’s zero evidence of any benefit for people who take resveratrol supplements. And you’d have to drink a hundred to a thousand glasses of red wine daily to get an amount equivalent to the doses that improved health in mice, he says. Also, a 2014 study of older adults living in the Chianti region of Italy, whose diets were naturally rich in resveratrol, found no link between resveratrol levels (measured by a breakdown product in urine samples) and rates of heart disease, cancer, or death. As for the Mediterranean diet, it’s impossible to know whether red wine is an important part of why that eating style helps reduce heart disease, says Dr. Mukamal.

If you enjoy red wine, be sure to limit yourself to moderate amounts. Measure out 5 ounces (which equals one serving) in the glass you typically use. Five ounces appears smaller in a large goblet than in a standard wine glass. Also, older men should be aware that both the National Institute of Alcohol Abuse and Alcoholism and the American Geriatric Society recommend that starting at age 65, men should limit their alcohol use to no more than a single drink per day. Age-related changes, including a diminished ability to metabolize alcohol, make higher amounts risky regardless of gender.
Some medical news stories don’t get the attention they deserve. Perhaps it’s because the disease is rare and not many people have ever heard of it.

I think this story about a new treatment for scleroderma is a good example.
What’s scleroderma?

The term “scleroderma” means “hard skin.” The name comes from the way it causes thickening and hardening of the skin. With “limited scleroderma,” the disease is mostly confined to the skin. With the “systemic” form of disease, other major organs, including the digestive tract, lungs, heart, and kidneys, may be affected as well. It is considered an “autoimmune disease”; there is evidence that the immune system of people with scleroderma is abnormal and appears to be attacking its host.
Better treatments are needed

Since the disease was first described by Hippocrates around 400 bc, reliably effective treatments have been unavailable. Existing treatments include moisturizers, medications to prevent heartburn and to improve circulation, and immune-suppressing medications. However, despite treatment, many people continue to suffer with bothersome symptoms and life-threatening complications such as severe scarring of the lungs or kidney failure.
A new study of stem-cell transplantation for scleroderma

Researchers publishing in a recent edition of the New England Journal of Medicine describe a new approach to treating severe scleroderma: stem-cell transplantation. With this treatment, stem cells (which can develop into many different types of cells) are removed and the body’s immune system is essentially wiped out with chemotherapy and radiation. The stem cells are then returned to the body where they rebuild the immune system — a sort of “rebooting” of the immune system.

It’s risky, especially soon after treatment begins, because there is a period of time in which the immune system doesn’t function well enough to protect the person from infections. In this study, 36 people with severe scleroderma received stem-cell transplantation and were compared with 39 otherwise similar people who received a year of standard immune-suppressing medication.

After 4.5 years, those assigned to receive stem-cell transplantation had

    improved overall event-free survival compared with standard treatment (79% vs. 50%); event-free survival means survival without serious lung, kidney or heart complications
    less need for immune suppressing medication (9% vs. 44%)
    more deaths related to treatment (3% vs. 0%).

These findings suggest that stem-cell transplantation may be much better than standard treatment for people with severe scleroderma even though it is riskier in the short run.
What’s next?

Despite these encouraging results, additional research is needed to identify those with scleroderma who are the best candidates for stem cell transplantation and to reduce the risk of this treatment. There’s still plenty of room for improvement: several study subjects treated with stem cell transplantation died within 5 years of treatment.  So, you can expect to hear about additional research that seeks to refine stem cell transplantation and other treatment approaches for scleroderma.

Scleroderma remains a mysterious and often deadly disease despite decades of research. So, you can also expect researchers to report on new findings regarding how and why it develops in the first place. In addition, stem-cell transplantation would not be appropriate for less severe cases of scleroderma; we need better treatments for them as well.

News such as this represents progress for a condition that badly needs it. While you may not have heard much about this study in the news, it’s certainly one that will catch the attention of people with scleroderma, their loved ones, and their doctors.
Depression is the leading cause of disability in the United States among people ages 15 to 44. While there are many effective treatments for depression, first-line approaches such as antidepressants and psychotherapy do not work for everyone. In fact, approximately two-thirds of people with depression don’t get adequate relief from the first antidepressant they try. After two months of treatment, at least some symptoms will remain for these individuals, and each subsequent medication tried is actually less likely to help than the one prior.

What can people with depression do when they do not respond to first-line treatments? For several decades, electroconvulsive therapy (ECT or “shock therapy”) was the gold standard for treatment-resistant depression. In fact, ECT is still considered to be the most potent and effective treatment for this condition, and it continues to be used regularly across the country. For many people with depression, however, ECT can be too difficult to tolerate due to side effects on memory and cognition. For those individuals and the many others who have had an inadequate response to medications and therapy alone, there is a newer treatment option called transcranial magnetic stimulation (TMS).
What is transcranial magnetic stimulation?

Transcranial magnetic stimulation, or TMS, is a noninvasive form of brain stimulation. TMS devices operate completely outside of the body and affect central nervous system activity by applying powerful magnetic fields to specific areas of the brain that we know are involved in depression. TMS doesn’t require anesthesia and it is generally exceptionally well tolerated as compared to the side effects often seen with medications and ECT. The most common side effect is headache during or after treatment. A rare but serious side effect is seizures, and TMS may not be appropriate for people at high risk such as those with epilepsy, a history of head injury, or other serious neurologic issues.
Does TMS work?

Approximately 50% to 60% of people with depression who have tried and failed to receive benefit from medications experience a clinically meaningful response with TMS. About one-third of these individuals experience a full remission, meaning that their symptoms go away completely. It is important to acknowledge that these results, while encouraging, are not permanent. Like most other treatments for mood disorders, there is a high recurrence rate. However, most TMS patients feel better for many months after treatment stops, with the average length of response being a little more than a year. Some will opt to come back for subsequent rounds of treatment. For individuals who do not respond to TMS, ECT may still be effective and is often worth considering.
What is TMS therapy like?

TMS therapy is an intensive treatment option requiring sessions that occur five days a week for several weeks. Each session may last anywhere from 20 to 50 minutes, depending on the device and clinical protocol being used. When patients arrive, they may briefly check in with a technician or doctor and then begin the stimulation process. The technician will determine the ideal stimulation intensity and anatomical target by taking advantage of a “landmark” in the brain called the motor cortex. By first targeting this part of the brain, the team can determine where best to locate the stimulation coil as it relates to that individual’s brain and how intensely it must “fire” in order to achieve adequate stimulation. Calculations are then applied to translate this data toward finding the dorsolateral prefrontal cortex, the brain target with the greatest evidence of clinical effectiveness and an area known to be involved in depression. Though one session may be enough to change the brain’s level of excitability, relief isn’t usually noticeable until the third, fourth, fifth, or even sixth week of treatment.
Can TMS help with other conditions?

TMS is being studied extensively across disorders and even disciplines with the hope that it will evolve into new treatments for neurological disorders, pain management, and physical rehabilitation in addition to psychiatry. There are currently large clinical trials looking at the effectiveness of TMS in conditions such as pediatric depression, bipolar disorder, obsessive-compulsive disorder, smoking cessation, and post-traumatic stress disorder. While promising avenues for research, TMS for these conditions is not yet approved and would be considered “off-label.”

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