New depression therapy intriguing

For years, severely depressed people have had one last resort if antidepressant drugs and talking therapy failed: ECT or electroconvulsive therapy — better known as “shock” therapy.

In ECT, electrodes placed on the scalp send electrical pulses to the brain, which, to be effective, must be strong enough to trigger a seizure. To prevent pain and injury from convulsions during the therapy, the patient is given general anesthesia.

Roughly 80 to 90 percent of the time, ECT works well, better, in fact, than drugs, which help in 60 to 70 percent of cases. Because of its effectiveness, 50,000 people a year turn to ECT.

But the downside, and it’s a big one, is that ECT causes confusion after treatments (three times weekly for several weeks), and memory loss, some of which may be irreversible. And mood may improve for only three to six months.

Now, however, brain researchers say they may have found another way to jolt the brain out of depression — TMS, or transcranial magnetic stimulation — that has many potential advantages over ECT. It’s still not clear whether TMS will be as potent as ECT, but it does appear to have fewer side effects.

With ECT, for instance, much of the electric current from electrodes is stopped by the scalp and skull. The current that does get through spreads through the entire brain, causing a generalized seizure — a kind of electrical storm.

In fact, if there’s no seizure, there’s no improvement in depression, perhaps because seizures trigger an increase in the brain chemical serotonin, just as many antidepressant drugs do, says Dr. Richard Weiner of Duke University, who heads the American Psychiatric Association task force on ECT.

With TMS, it’s not an electric current but a magnetic field that passes through the brain, generated by a coil of wire that’s placed on the head and turned rapidly on and off. The magnetic field then excites nerve cells in the brain — only where it is aimed, usually the left prefrontal cortex (behind the forehead), where electrical activity is often abnormal in depressed people.

Not only can TMS be precisely targeted, it does not cause seizures or memory problems, and anesthesia is not necessary. “Those are huge plusses,” says Dr. Alvaro Pascual-Leone, a neurologist at Beth Israel Deaconess Medical Center.

TMS is still experimental, which means that if you want to try it, you have to participate in one of the clinical trials now under way around the country. Worldwide, it has been tried in only about 1,000 people, says Dr. David Avery, associate professor of psychiatry and behavior science at the University of Washington.

In fact, published data exist on only 200 patients, says Dr. Mark George, a psychiatrist, neurologist and radiologist, at the Medical University of South Carolina.

And only two of the published studies — involving a total of 29 patients — were double blind, that is, designed so that neither patients nor researchers knew who was getting real TMS and who was getting a sham procedure in which the brain was not stimulated. Even in these studies, the technicians knew which patient was getting what.

Despite all these caveats, the early findings have set brain researchers buzzing, most recently at a Society of Biological Psychiatry meeting 10 days ago in Toronto.

In a study of 17 patients published in 1996 in the British medical journal Lancet, for instance, Pascual-Leone said patients given TMS showed a 50 percent improvement on a commonly-used depression rating scale. “That’s better than any antidepressant ever, better than ECT. It’s a remarkable efficacy in any time frame, and these were psychotically depressed people,” said George.

In a larger study presented at the meeting, Pascual-Leone got a 60 percent response when he treated people with TMS for 10 days (not five, as in his earlier study) and the benefits lasted several months.

George’s double blind study of 12 people, published in the December 1997 issue of the American Journal of Psychiatry, was a bit less dazzling. After two weeks of TMS, patients scored about 20 percent better on depression tests.

But his new results on 30 patients, also presented in Toronto, were more encouraging: a nearly 50 percent improvement in depression for patients given low frequency TMS. (Those given high frequency TMS fared less well, showing only a 30 percent decrease in depression, which was similar to those who got sham treatment.)

The emerging data on TMS is exciting to researchers and doctors in part because depression is so common. Over a lifetime, 7.4 percent of women and 2.8 percent of men suffer a bout of major, incapacitating depression. When less serious forms of depression are included, one quarter of women have an episode at some point in life, as do 15 percent of men.

Also encouraging, researchers say, is the suggestion that TMS may be also useful for other illnesses that affect the brain, including post-traumatic stress disorder, obsessive-compulsive disorder, and perhaps Parkinson’s disease.

But TMS is of intense academic interest as well because of the light it could shed on the brain disruptions believed to be present — as the cause or the effect — in depression.

PET scans of depressed individuals have shown a decreased blood flow to the left prefrontal cortex, along with decreased metabolism of glucose, says Dr. Holly Lisanby, a Columbia University psychiatrist who is starting a study of combined TMS and drug therapy.

The theory behind magnetic stimulation, says Dr. Eric Wassermann, a neurologist at the National Institute of Neurologic Disorders and Stroke, is that it boosts the excitability of these prefrontal nerves, that is, it kind of jolts them out of their sluggishness.

But depression is so complex that other areas of the brain are undoubtedly involved, too, including the cingulate gyrus, which lies deep in the limbic system (which controls emotion).

In other words, much as they’d like one, scientists still have no grand theory to explain how vastly different treatments for depression — drugs, ECT and TMS — may act on different regions of the brain but all produce an improvement in mood.

“If we can figure out what TMS is doing,” says George, “we are almost there in terms of understanding depression. That is the driving hope I have, an addition to finding what might help a lot of people.”


For more information on transcranial magnetic stimulation, you can visit the web at

If you want to enroll in a clinical trial, including a multi-center trial testing a combination of TMS and anti-depressant medication, you may call Dr. Alvaro Pascual-Leone at 617-667-0203.