Sunday, July 27, 2008
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The shock that saves

Emory scientists turn on the juice to heal depressed patients

Emory neuroscientist Helen S. Mayberg, co-inventor of a deep brain stimulation procedure to treat depression.
Courtesy of Emory University

By Stephanie Ramage


For decades, doctors have intentionally damaged certain parts of the brain to lessen symptoms of mental illness. In general, when one area of the brain is damaged, it naturally tries to compensate by using another part, so a person who’s had that kind of operation can usually continue going about his or her business fairly normally. The problem, says Emory University neuroscientist Helen S. Mayberg, is that “a hole in the brain is a hole in the brain”—it doesn’t heal, and there can be complications.

So researchers started thinking about electrically stimulating parts of the brain instead of trashing them. Deep brain stimulation, or DBS, was first used in France in 1987 to treat involuntary tremors. The therapy was approved by the FDA in 2002 for treatment of tremors associated with advanced Parkinson's disease, which encouraged Mayberg, then on faculty at the University of Toronto, to try DBS in treating major, prolonged depression. She says her team agreed to take only the most treatment-resistant patients, people who were so depressed that they were completely functionally disabled. Candidates for the treatment had to have tried every alternative available to them: talk therapy, drugs, and even electroconvulsive therapy—better known as “electroshock therapy”—without success.

“We didn’t know what to expect,” says Mayberg. “The first patient, on the second electrode’s contact—we got up to about four volts—she said, ‘Did you do something? I suddenly have this sense of calmness and relief.’ She suddenly felt as if someone had removed a weight from her chest. It was really, really amazing. The patients felt relief from their version of psychic pain, and you could see it. Maybe they just felt less emptiness.”

The Toronto team used the procedure on six patients, four of whom reported improvement. Eventually they expanded the study to 20 people. Sixty percent reported improvement. In treatment-resistant depression, as in most illnesses, a 60 percent improvement rate makes the scientific establishment take notice. 

Last week, the online issue of Biological Psychiatry reported the results of the study, which showed the procedure is “safe and provides significant improvement in patients as early as one month after treatment,” according to a statement issued by Emory University.

Mayberg initiated an expanded version of her Toronto study at Emory in 2007 with psychiatrist Paul Holtzheimer and neurosurgeon Robert Gross, with grant support from the Woodruff Fund, the Stanley Medical Research Institute and the Dana Foundation.

The new Emory clinical trial includes patients with bipolar II depression—a kind of bipolar disorder that has slightly less dramatic manic episodes than the classic bipolar disorder. The study will be conducted over a period of at least three years.

“The New Lobotomy?”

When Mayberg’s DBS method was tested on depressed patients in Vancouver in 2006, one Canadian newspaper published an article about it titled, “The New Lobotomy?” Mayberg herself doesn’t shy away from discussions of psychiatric surgery, but the differences between a procedure that uses an electrical current to regulate brain activity and one that actually disconnects part of the brain are striking.

Consider the horrific case of Howard Dully, made famous in a 2005 National Public Radio segment titled “My Lobotomy.” In it, Dully recounts how at the age of 12, he was subjected to an “ice-pick lobotomy” at the hands of the man widely credited with inventing the lobotomy, Walter Freeman.

The procedure was actually invented in 1936 by Egas Moniz, a Portuguese surgeon who bore an eerie resemblance to ’60s television character Herman Munster. Moniz called the surgery a prefrontal leucotomy.

Freeman devised a variation on Moniz’s operation: He performed it with an ice pick (his son would later say that the one used in the first of his father’s operations came right out of the family’s kitchen drawer) and called it a lobotomy, since it severed the prefrontal lobe from the rest of the brain.

Freeman would pull up the patient’s eyelid and tap an ice-pick through the thin orbital bone into the brain, then move it “in an eggbeater fashion,” disconnecting the lobe from the rest of the brain. Dully described how his stepmother complained to Freeman that her stepson didn’t like to wash and irritated her by turning on light switches when he didn’t need to, which prompted Freeman to suggest that she might want to “change” young Howard’s personality by allowing the doctor to jam an ice pick into the boy’s skull and scramble his prefrontal lobe. Dully endured the operation in 1960.

Dr. Freeman’s cross-country lobotomy tour—he performed some of his 2,500 “trans-orbital” lobotomies out of a van and would sometimes do two-fisted lobotomies with a pick in each hand—wasn’t the first mind-blowing experiment in mental health (Bethlehem Royal Hospital, with its chained mental patients kept on display for public entertainment, lives on in our language in the word “bedlam”). And it wouldn’t be the last. Just a few years after Dully’s lobotomy, poet Sylvia Plath would publish an account of her own electroshock therapy in the semi-autobiographical novel, “The Bell Jar.” She described it as a procedure that brought calm to the troubled mind of protagonist Esther Greenwood. But it was depicted in the 1975 film “One Flew Over the Cuckoo’s Nest” as torture used to bring rebellious patients into submission.

“It’s easy to be judgmental or to condemn the things that were done,” says Mayberg. “But you have to remember drugs were not in wide use then, and the mental institutions were packed. People were desperate for help.”

Psychiatric drugs were first made widely available in the United States in the ’50s, and were soon introduced into pop-culture consciousness in the lyrics of songs like the Rolling Stones’ “Mother’s Little Helper.” But it wasn’t until the ’90s that antidepressants came to define middle-class America. Prozac, which has itself become a word that signifies Yuppie pacification, inspired Elizabeth Wurtzel’s 1994 bestseller “Prozac Nation.” When numerous reports surfaced that some patients using Prozac became suicidal, its allure wore off a bit.

Now, a variety of drugs are used to treat everything from depression to anxiety to lack of focus to lack of sexual interest. If Dully had been born a few decades later, his stepmother might have dosed him with drugs instead of asking Freeman to plunge in the pick. The effect probably would have been the same.

The approach to mental health may have changed since 1960, but the devastating effects of depression have not.

According to the American Foundation for Suicide Prevention, almost 30,000 Americans commit suicide each year, and of those, half have been diagnosed with depression. Suicide is the ninth leading  HYPERLINK "http://www.livescience.com/environment/050106_odds_of_dying.html" cause of death in the United States. In fact, the American suicide rate is higher than the homicide rate. As Benjamin Radford, managing editor of Skeptical Inquirer magazine, puts it, for every murder you hear about, there are two suicides you don’t hear about. Most studies put the suicide rate among the depressed at about 15 percent. But, researchers at John Hopkins University have reported that for those with schizophrenia and bipolar disorder, it’s higher: about 19 percent threaten or attempt suicide.

One man’s shocking solution

DBS uses electrodes to send a small electrical current through the limpid area of the brain, a place known as “Area 25.” To get there, a surgeon makes a hole in the patient’s skull that’s a little smaller than a quarter. Through this hole, the surgeon maneuvers a wire the size of a piece of linguine with four tiny electrodes on the end. The other end of the wire is attached to a battery that’s implanted just below the patient’s collarbone.

“It’s like a pacemaker for the brain,” says Mayberg.

If the apparatus is removed, she says, the effects wear off in a few weeks.

The idea of sending electrical currents through the brain to temporarily alter its function dates back to the ’30s, when Hungarian neuropsychiatrist  Ladislas J. Meduna used electroconvulsive therapy (ECT) to treat schizophrenia.

 “It has changed a lot since then,” says Adriana Hermida, an assistant professor of psychiatry and behavioral sciences at Emory. “It used to be that when patients convulsed they could break bones, but today we use a general anesthetic, so the convulsion is really in the brain; you don’t actually see it happening to the patient.”

Hermida recommends ECT in cases where drugs have not proven effective and a quick result is needed to snap a patient out of suicidal thoughts or debilitating depression.

That was the case for Jerry Bishop’s son. The 27-year-old Atlantan, who suffers from schizophrenia and major depression, found the treatment while desperately researching an alternative to the barrage of drugs he took every day. Normally weighing in at about 165 pounds, he ballooned to 250 pounds as a result of side effects of the drugs.

“He would also have to take something to be able to sleep because some of the drugs interfered with that, and then he would hallucinate as a side effect to the drug he had taken to sleep or the combination of drugs,” his father explains. “He found ECT. He said ‘I want to try this.’ He had tried everything else.”

Bishop had misgivings, but his son, who seemed to be deteriorating before his eyes, convinced him to help him seek the treatment.

“We took him to Emory, they prepped him, put an IV in his arm to sedate him and then took him back, and when he came out, there was a little smile on his face and a bounce in his step,” says Bishop. “It was really just that quick.”

He has now completed more than 60 sessions of ECT. At first he had six—one on Monday, Wednesday and Friday for a two-week period—but now he has only one monthly maintenance session. His drug regimen has been cut in half.

“It works,” says Hermida. “It’s interesting to me that people are willing to have brain surgery—which is what deep brain stimulation is—but they are afraid of electroconvulsive therapy.” SP