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November 17, 2003
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Shock therapy and the brain
* New studies on the treatment for depression emphasize uncertainty about its effects.

Shock therapy and the brain
Shock therapy and the brain
(Photo illustration by Jonathan Barkat / For The Times)
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By Benedict Carey, Times Staff Writer

The electrical current throbs from one side of the skull to the other, scrambling circuits along the way, inducing a brief seizure. When it's over and the anesthesia wears off, patients often are subdued, confused, sometimes unsure of where they are or why. Then, sometimes, the remarkable happens: Severely depressed people find that the darkness has lifted; they feel better than they have in years.

Others are left distraught. They've been shocked and feel no better than before.

In recent decades, electroconvulsive therapy, or ECT, has undergone a transformation, many psychiatrists say. The body no longer thrashes violently, as depicted in movies a generation ago; it lies still, under medication, with the thrashing confined to the mind. Techniques are more precise, they say; the brain better understood.

Although exact numbers are not available on how many people get modern ECT estimates have ranged from 30,000 to more than 50,000 a year since the early 1990s scientific interest in the treatment has surged, in part because of the acknowledgment that drugs don't help many deeply depressed people, particularly older adults, a growing and hard-to-treat population. The government is funding some 20 ECT studies to see how different techniques and treatment combinations affect behavior.


Altering biology

Recently, researchers have looked directly at how the bolts of current alter biology, by studying the brains of shocked rodents. And in June, a leading medical journal published the results of a broad survey detailing what former ECT patients think about the treatment.

Yet far from proving the effectiveness of ECT, the emerging research has only accentuated its unknowns and shortcomings. After more than 60 years of experience, doctors still don't know exactly how the shocks affect the brain, whether they cause permanent damage, or why they affect depression. Although the techniques and technology have improved, ECT itself appears no more effective than it ever was, studies show.

When it comes to treating older people in particular, doctors have no scientifically rigorous evidence establishing the treatment's safety or effectiveness, according to an exhaustive review of the literature published last month. "Proponents have been saying it's safe and effective, but their statements go beyond what we know for elderly people," said John Bola, a mental health researcher at USC who studies treatment effectiveness. "It starts to sound more like an advertisement than a statement of fact."

The reputation of shock therapy has alternately risen and fallen since 1938, when an Italian psychiatrist named Ugo Cerletti decided to try shocking one of his patients, a 39-year-old man, after watching slaughterhouse workers subdue pigs with bolts of current delivered to the brain, and after first experimenting on animals. Cerletti reported that the man improved after repeated shocks, and the idea soon caught on among doctors desperate for some way to manage disturbed, often aggressive, patients. Use of the treatment then declined through the 1960s and 1970s, due to the introduction of new psychiatric drugs and the public stigma attached to the therapy.

That decline stopped in the 1980s, researchers say, because psychiatrists refined their techniques and continued to report recoveries in severely depressed people who didn't respond to any other treatment. By 1990, an American Psychiatric Assn. task force report on ECT concluded that the treatment was highly effective, "with 80% to 90% of those treated showing improvement." The association also set precise guidelines for treatment, specifying the amounts of electricity and placement of electrodes that seemed to produce the best results.

"You're talking about people who are desperate, who are often suicidal, who have just about lost it all," said psychologist Harold Sackeim, chief of biological psychiatry at the New York State Psychiatric Institute and a professor at Columbia and Cornell universities in New York. "This is a treatment that we know can help them turn it around, and it is very satisfying to see that happen."


Relief usually temporary

Psychiatrists acknowledge that the mood-altering effect of ECT is usually very short-lived: Those who do feel better after a series of shocks almost always plunge back into depression within a few weeks, or months. Aggressively treating these people with drugs can help; but it is hardly a guarantee that the depression will lift, or that a person will agree to endure such treatment in the first place.

"It must be thought of as a stopgap measure in life-threatening situations," said Dr. Jeffrey Schwartz, a research psychiatrist at UCLA's Neuropsychiatric Institute. "All you're doing is buying more time to get to a place where drugs, or cognitive therapy, can have some effect."

In an article in the March 14, 2001, Journal of the American Medical Assn., researchers at Columbia University in New York reported that a combination of ECT and aggressive drug treatment successfully vanquished depression in 14 of 23 people (61%) for at least six months. This is a significant improvement, and far more effective than ECT alone, which helped only four of 25 people in the study (16%) for six months.

But the researchers also reported that more than half of the 316 people originally enrolled and given shock therapy dropped out of the study, or were excluded. Most of these people didn't feel at all better after the shocks; others refused further treatment; and some suffered medical complications. The success rate of the treatments is based only on the fraction of the people who both responded well to the shock and had no adverse reactions or second thoughts. Without continual therapy of some kind, the authors conclude, "almost universal relapse should be expected."

Some psychiatrists believe that the solution for this is more ECT. Continuation-ECT, or C-ETC, as it's known, involves "maintenance" shock sessions every every three to six months, or whatever seems best suited to the patient. Some psychiatrists have been providing C-ECT for years, and hundreds of people are already on this steady regimen, experts estimate.

Yet there's no scientifically rigorous evidence that continually shocking a person is safe, and it could cause damage, some doctors say.

In several recent studies in rats, scientists have reported some of the first direct evidence of biological changes from the treatments that might be related to changes in behavior. They report that ECT accelerates the production of new brain cells in these animals and spurs the growth of neural connections called mossy fibers. Some ECT doctors say new neurons are probably helpful and that new nerve connections may enhance brain function.

"These changes could help explain how it is that these severely depressed patients recover," said Dr. Sarah Lisanby, a Columbia University psychiatrist who heads the American Psychiatric Assn.'s ECT Committee.

Lisanby acknowledges, though, that doctors aren't sure whether the brain changes are good or bad. The studies purporting to show brain cell proliferation due to ECT may in fact be showing evidence of brain cell damage, according to Richard Nowakowski, a neuroscientist at the Robert Wood Johnson School of Medicine in Piscataway, N.J., who pioneered the use of the cellular techniques used in the experiments. "It's not clear in these studies whether they're seeing proliferation or something else," he said. As far as what the changes actually mean, he said, "anyone who tells you they know doesn't."

Nor is it clear what the growth of these new neural connections means. Neuroscientists say that the brain's nerve networks are laid down over years, as the brain develops and responds to the outside world. The chances that an instantaneous, shock-induced fiber would make exactly the right connections to enhance function, they say, are extremely remote. Moreover, the kind of neural sprouting, or mossy fiber proliferation, observed in shocked animals also turns up in the brains of people who have epilepsy, a neurological disease in which the body suffers periodic, unexplained seizures. "In this area, there's a debate over whether the epilepsy causes the fibers, or the fibers cause the epilepsy," said Nowakowski.


Patients' reactions vary

The men and women on the receiving end of the electrodes vary widely in their judgment of the effect. Some are grateful for the treatment, and insist that the shocks both relieved their illness and improved their cognitive function. Others are outraged. Over the years, the practice of ECT has spawned a large and vocal group of critics who say the shocks harmed them, mainly by erasing memory.

"There are thousands of people out there who feel they weren't told the whole story before getting the treatment," said Juli Lawrence, 44, a St. Louis-based freelance writer who started the Web site ect.org after a series of shock treatments failed to lift her depression and obliterated about two years of memory.

In the first large-scale effort to learn from ECT patients themselves, researchers in England reviewed 35 studies of patient attitudes. All told, the studies involved more than 2,000 men and women who got ECT treatment in the last two decades or earlier. Depending on the study, 30% to 80% of former patients reported lasting memory loss. In one survey, a third of patients agreed with the statement, "Electroconvulsive therapy permanently wipes out large parts of memory." The proportion of people who considered the treatment ultimately helpful varied just as widely from about one-third, when patients helped design or conduct surveys; to about three-fourths, when doctors did.

"This is what happens when you ask patients what they think," said patient turned prominent ECT critic Linda Andre, who has questioned ECT research and practice. "You get a completely different story from the one psychiatrists are telling."


Weighing benefits, risks

Dr. LOREN MOSHER, former director of schizophrenia research at the National Institute of Mental Health and now a clinical professor of psychiatry at UC San Diego, said the issue comes down to a "cost-benefit" analysis. "Does it make sense to expose people to something which not only isn't very effective but also has serious inherent danger? In my view, the cost to the person is greater than the potential benefit."

Until doctors find an answer for severe depression whose costs are not so steep, the controversy is not likely to diminish. Drug companies have been working to find better antidepressants for years, so far without significantly improving on what's been available for the last 10 years or so. Now, Lisanby and other researchers are investigating the possibility of using magnetically induced convulsions as an alternative to electricity. A strong magnetic field near the head can also induce a brief seizure. The hope is that the magnetic stimulation might "break" the depression in the same way ECT does, but for longer than a few months or weeks and without the memory loss.

"ECT is an important treatment, and has helped to save the lives of many patients, many of my own patients, but we need to do better, to find treatments that are more tolerable and accessible," Lisanby said.

In order to determine safety and side effects, doctors at Columbia and the New York State Psychiatric Institute induced brain seizures in 10 severely depressed men and women with bursts of magnetic stimulation. They report that these shocks induced fewer memory problems than ECT.

As for the effect on depression, psychiatrists in Europe have reported on one person who got a full treatment course of magnetic shocks. A 20-year-old woman, she felt an almost immediate lifting of her mood, according to psychological measures done after the treatment.

But to prevent relapse, doctors decided she needed further treatment with ECT.

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