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New Hope for Severe Depression
by Cynthia Shyev Riskin

On March 7, I chatted about Labrador retrievers with Mindcare Centres director Iain Glass for half an hour while he shot 2,500 high-powered magnetic jolts into my brain with a figure-eight coil wrapped in plastic. After 30 such treatments, called repetitive transcranial magnetic stimulation (rTMS), I am in remission from more than 30 years of depression, which derailed my Cornell University education, ended a five-year relationship, stymied my career and robbed me of hope for a worthwhile future.

Two months later, I am still in remission – and every day offers hope and excitement. Like most Mindcare patients who go to Vancouver, B.C., or Toronto for the $200-a-session treatments not yet approved by the FDA (they have been available in Canada since 2002), I had tried nearly everything for my depression. More than a dozen psychiatrists and psychotherapists had applied varying pharmaceutical cocktails and behavioral, cognitive and other therapies over three decades. I had tried acupuncture, yoga and herbal remedies. I had changed diet, exercise habits, spiritual practices, job, relationships, body size, living arrangements and coasts.

“These people have tried virtually everything,” said Glass of his clients. “We’re pleased because we’re getting a very high response rate in the toughest population.”

rTMS Research
University of Washington professor David Avery, director of inpatient psychiatry at Harborview Medical Center, is studying rTMS under a 2004 National Institute of Mental Health (NIMH) grant here in Seattle. rTMS is also being studied at the Medical University of South Carolina, Emory University and Columbia University. This research on medication-resistant depression sufferers requires double-blind controls (neither the study administrator nor the subject know whether the treatment is real or placebo) and that the participants stop taking psychotropic medications, except for benzodiazepines, which are used mostly as sedatives or tranquilizers.

The risk for me was too great. I was on Serzone, Zoloft and Wellbutrin (to cheer me up); Clonapin and a smidgen of Seroquel (to calm me down); and Ritalin (to pep me up). I was worried that I might end up suicidal, land in a hospital and still not be guaranteed an rTMS trial until the end of the study, when all participants receive the actual stimulation. Last time I was in that condition, it took a hideous weeklong hospital stay and five years to return to my version of normal.

“There are safety and ethical issues associated with the style of trial the FDA wants,” said Glass, who is poised to open Mindcare Centres in the United States as soon as the FDA approves rTMS, which he expects to occur within two years. (Avery estimates three years until FDA approval.)

Study subjects need to stop taking antidepressants so that any mood improvements can be attributed only to rTMS. Without a control group, in which an inactive stimulus is applied instead of true rTMS, it would be impossible to determine whether patients improved because of the treatment or because they believed that they were being treated.

The FDA has been cautious about approving rTMS because until now, the studies have been small, with about 20 to 30 subjects, says Avery, whose 2000 NIMH study used 68 subjects. If an incidence of a serious side effect is 1 in 10,000, you might need to test 10,000 people before that side effect shows up.

“I think agencies like the FDA tend to be very conservative,” says Avery. “I think that they want to make sure that treatments that are available to the population are, number one, safe and that there are no detrimental effects. Or if there are side effects, that they’re well characterized [understood and described]. That requires a lot of studies.”

One Flew over the Cuckoo’s Nest
One of the more accepted – although highly stigmatized – therapies for medication-resistant depression is electroconvulsive therapy (ECT), which seems to have more side effects of greater severity than rTMS. ECT electrically stimulates the entire brain, including memory centers, while rTMS applies a focused magnetic pulse to a small area of the brain. ECT can cause temporary, or even permanent, memory loss. It also requires general anesthetic and a powerful muscle relaxant to prevent inadvertent injury from convulsions.

“Even though I administer ECT and see people have miraculous transformations afterwards, I also see its limitations due to confusion and temporary memory loss,” says Avery, as reported on the UW Web site. “The possibility of achieving the benefits of ECT without the side effects is very appealing.”

rTMS may be nearly as effective as ECT in treating nonpsychotic major depression. Six out of seven studies comparing the two showed similar results of 40 to 60 percent improvement, says Avery. There is no way to predict who will respond favorably to rTMS, although greater age, longer depression, and the more medication trials a subject has failed may make him or her less likely to respond. (The age cutoff for the UW study is 70; Mindcare Centres reports no age correlation.)

With “the lowest side-effect profile of current [depression] interventions,” according to Glass, rTMS appears to have fewer and less serious side effects than ECT. Neuropsychological tests at Harborview showed no diminishment of attention and concentration in rTMS patients. One of the worst side effects currently known is that rTMS treatments can cause a headache that goes away within several hours.

I felt that headache, all right. The treatment itself felt like dozens of hits by a nail gun to an area a few inches above my left temple until I started to get used to it later in my treatment. My lab-mix, Sabra, occasionally sat on my lap during treatments for emotional support. And on a few occasions, all I needed were a couple of Tylenol to make me feel well enough to enjoy a trip to the dog park or an arboretum immediately after my session.

All in the Head?
Depending on what part of the brain rTMS is aimed at, it can either stimulate or calm brain activity. Major depression is frequently associated with slower glucose uptake and lower blood flow in the dorsolateral prefrontal cortex (DLPFC), a part of the brain under the scalp and a few inches above the left temple, and increased activity in the limbic system (a group of brain structures that affect emotion, memory, hormones, and involuntary body functions, such as heartbeat and breathing). Both play roles in regulating mood. rTMS induces a magnetic current in the DLPFC, which is thought to increase the levels of dopamine and serotonin levels (chemicals that transmit nerve impulses that are believed to enhance mood), although exactly how it works is unknown.

Sluggish glucose metabolism and reduced blood flow in depressed areas of the brain can be demonstrated using various brain imaging methods. I found it tremendously reassuring that depression could actually be shown – that I wasn’t, as I had previously suspected, depressed because I was a crappy person.

“Depression is very real,” says Glass. “Just because people can’t see it doesn’t mean it doesn’t exist . . . What’s unfortunate about depression is that society is almost criminal in its attitudes toward depressed people.” People are more likely, he notes, to empathize with someone wearing a cast, whereas, “If you walk into a room and say you’re depressed, you have a credibility issue with a large number of people . . . So as a society we need to be far more aware; we need to do far more in terms of education.”

rTMS may also help synchronize the functions of the left and right brain hemispheres – although the exact mechanism is unknown. In fact, much about rTMS is still under investigation in not only the United States, but also England, Scotland, Sweden, Israel and elsewhere. With several variables to play with – exact stimulation site, pulse speed, pulse pattern, intensity of stimulation, and number of stimulations per session – protocols for treatment vary from place to place. On me, Mindcare Centres used 10 pulses per second for five seconds, followed by a 20-second rest, with an intensity of 120 percent of motor threshold (the point at which the pulse triggers the right thumb to twitch half the time), for a total of 2,500 stimulations per half-hour session. After a half-hour rest, we did it a second time.

After the first week, my Beck Depression Inventory scores dropped from 34 (severely depressed) to 21 (moderately depressed). My energy and sociability increased to the point that I exhausted myself over the weekend and mildly relapsed the following week.

Usually, the center recommends 20 treatments if they seem to be working. But after 20 treatments, my score was a 12 (mildly depressed), still four points shy of remission, which Glass considers a score of 8. So I stayed in Vancouver a third week, until I had 30 treatments under my belt and was depression-free, with a score of 6.

The UW NIMH study, for which Avery is recruiting for the next three years, will use a similar protocol. With some differences in pulse pattern, total stimulations per day, and treatment duration, which will vary from 15 to 65 days, there will be one treatment each day.

rTMS is also under investigation for such far-ranging conditions as anxiety, Alzheimer’s, Parkinson’s disease, obsessive-compulsive disorder, bipolar disorder, post-partum depression, stroke recovery, acute brain trauma, auditory hallucinations, fibromyalgia, eating disorders and smoking cessation.

Not a Cure-All
Although rTMS is promising, it is not a magic cure. Other factors, including stress, lack of exercise, poor diet, and disturbance of daily rhythms can affect mood. I start feeling crabby, for instance, when I eat too much sugar, stay up until 4 a.m., and don’t get enough exercise (no big surprise). Exercise creates an environment in which new brain cells can be created, and stress destroys brain cells, says Glass.

Avery finds that many of his mood-disordered patients have disturbed light-dark cycles and recommends that they dim all lights, including computer monitors, two hours before bedtime. He postulates that the increase in unnatural lighting sources over the past 50 years may be contributing to increased depression.

Use It or Lose It
My biggest fear is that I’ll lose my gains from rTMS, as Charlie lost his newfound genius in Daniel Keyes’ classic, Flowers for Algernon.

Avery’s team found a 50 percent relapse rate after six months, so he recommends starting antidepressant medication after rTMS. I’ve dropped or reduced some of my medicines under my psychiatrist’s care, but will have to stay on something, I suppose. And I may have to return to Vancouver for “touchups,” although there’s no telling how often or for how long. Mindcare Centres suggests a patient may have to return for a second treatment after an average of eight months.

With stronger exposure and more treatments, the duration of the effects of rTMS may increase. So I’m hoping that my extra 10 treatments will buy me some time or that my decades of skills learned in therapy will help me keep from backsliding.

©2005 Caliope Publishing Company