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Deep brain stimulation promising in treatment of chronic depression: study

28/02/2005 6:22:00 PM

TORONTO (CP) - A Canadian research endeavour may offer a glimmer of hope for people suffering debilitating treatment-resistant depression.

A team of Toronto researchers has shown in a small study that deep brain stimulation - the implantation of electrodes that provides continual stimulation to a part of the brain - can stir some patients out of chronic depression and allow them to resume the activities of daily life.

Jeanne Harris, 50, has battled the illness for the better part of a decade. About 10 per cent of people with chronic depression do not respond to treatment and Harris was among them. Despite taking a cocktail of drugs, she was incapable of working or even maintaining contact with friends.

In one six-month stretch, she travelled from bed to couch and back, bathing and changing her clothes only on the one day a week she was taken to see her doctor.

Nearly two years ago Harris became the first patient to undergo surgery to have two thin wires with electrode contacts threaded into the subgenual cingulate region deep within the frontal lobes of her brain. The ends of the wires were then tunnelled through to the lower neck area, where they were hooked up to a pacemaker-like device placed under the skin.

As the surgeon, Dr. Andres Lozano of Toronto Western Hospital, gentle probed different spots within the section, Harris - who was conscious throughout - was infused with an intense, almost forgotten, sense of serenity.

A few hours later, she was home clipping hedges. A minor task. A major miracle.

"It was absolutely unbelievable - to do it and to be feeling normal and enjoying it like I remember I used to feel," she recalled in an interview Monday.

Harris has had no side-effects from the surgery and raves about the procedure that gave her back her life.

"I see it as a major medical breakthrough. I see it as it saved my life because I was definitely headed towards suicide, because a person can only take so much."

The work is led by Dr. Helen Mayberg, an internationally renowned neurologist who specializes in the effect of depression and depression therapies on the brain. Mayberg led this study while she worked as a senior scientist at Baycrest Centre for Geriatric Care in Toronto; she is currently a professor of psychiatry and neurology at Emory University in Atlanta, Ga.

She admitted she was uncertain what the outcome would be when she got approval to try deep brain stimulation on this type of patient. The procedure is used with success to mitigate symptoms of Parkinson's disease, severe epilepsy, dystonia and other neurological conditions.

The findings - published this week in the journal Neuron - are preliminary, but impressive.

"It's a very small number of patients so we wouldn't want to draw huge conclusions from it. But in that small sample, yeah, that's a very encouraging result," said Dr. Robert Cooke, a psychiatrist in the depression clinic of Toronto's Centre for Addiction and Mental Health. Cooke is not involved in Mayberg's study.

Mayberg and her team reported that four of six patients have had considerable alleviation of their depression during deep brain stimulation. Two patients did not experience benefit and had the cables and devices removed.

"You never want to get overly excited with such a small number," Mayberg said from Atlanta.

"But this is not like you're having to squint and massage the numbers to convince yourself you've had an effect. . . . These people are well. And they've stayed well. They're out and about, getting back to living in the world."

Which is not to say they don't still have some problems. Harris admitted she still suffers the occasional relapse, but the depressions are short in duration and she can work her way out of them.

Mayberg said she believes what the stimulation does is jam overactivity in the subgenual cingulate, which then allows the rest of the brain to function more normally. Rather than making the patients happy, it appears to be removing an obstacle that had stopped them from experiencing the normal range of emotions.

"It's not a happy pill," she insisted. "It's something that turns off the negative."

But the brain has to relearn how to cope with the range of emotions, Mayberg suggested, likening the work patients must do post-implantation to the rehabilitation cardiac patients go through after bypass surgery.

"These are people who have lost the dynamic range to separate illness from real life. And they need to relearn that."

As for Mayberg, she too has work to do. A study of this size is considered "proof of principle" only.

"Now the hard part comes," she said.

"We need to do more patients. We need to figure out who really are the patients who are most suitable for this. We need to figure who are the patients who aren't suitable for this."

This article originally appeared as an MSN Health feature article.

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Brain stimulation may treat resistant depression

Dr. Andres Lozano discusses the new study during an interview with CTV News.

language=javascript type=text/javascript> var byString = ""; var sourceString = "CTV.ca News Staff"; if ((sourceString != "") && (byString != "")) { document.write(byString + ", "); } else { document.write(byString); } </SCRIPT> CTV.ca News Staff

Updated: Tue. Mar. 1 2005 10:37 AM ET

A team of Toronto researchers says it may have found a way to offer hope to the millions of people suffering long-lasting clinical depression who have been resistant to conventional treatment.

The researchers say they have had promising results from a study on deep brain stimulation (DBS). The researchers believe the method acts as a "brain pacemaker" to make depressed people happy again by electronically stimulating the brain.

The experiment is thought to be the first demonstration of drug-free electronic mood control.

The researchers behind the study emphasize more trials are needed but hope the method could offer a new therapy for millions suffering clinical depression who have not responded to drugs, psychotherapy, or electroconvulsive therapy.

For the study, patients with untreatable clinical depression had electrodes surgically implanted deep in their brains to stimulate the brain's the subgenual cingulate region -- one of the areas involved in mood control.

The patients then had a pulse generator implant -- the pacemaker -- sewn under the skin in their chest. The wires were hooked up to provide constant brain stimulation.

The results have been described by those involved as "like a miracle."

All six volunteers reported acute effects once the current was switched on, including noticing a sudden brightening of the room and a sense of heightened awareness.

Significant clinical response was seen in four of the six study subjects, with sustained improvement through six months.

Before the treatment, the patients were deeply depressed, lacking motivation, refusing to get out of bed for days and often feeling suicidal.

"These people weren't just having a bad day," explained Dr. Helen Mayberg, a neurologist who led the research. "They were beyond suicidal; they were too apathetic and disengaged to be bothered. They described their state as dead and deader."

Afterwards, some of the test cases started going to the gym and established new businesses. And, unlike psychiatric medications, there were no psychological side effects.

For years, Rob Matte was so depressed he couldn't get out of bed.

"I couldn't work. I couldn't physically take care of myself. I couldn't bathe. I wouldn't eat," Matte told CTV's Avis Favaro.

After medication and shock therapy failed to work, Matte tried DBS and now says his depression is gone.

"The magnitude of the benefits we have seen are so striking that most patients and their families, when they see it . . . will be interested in this surgery," said Toronto Western Hospital surgeon Dr. Andres Lozano.

Two other patients, both men, lapsed back into depression within six months. But the researchers believe that fine-tuning the treatment could eventually help most cases.

The researchers believe their technique works by modulating electrical activity in the brain mood control centre.

"Our study shows that areas of the brain that are on overdrive in patients with severe depression can be pinpointed, turned down and brought to a more normal level of activity using electrical stimulation," explained Lozano. "This in turn can lead to a lifting of depression in certain patients."

While DBS has been used to treat other brain disorders such as epilepsy and Parkinson's disease, this is the first report of DBS in the subgenual region for major depression.

The treatment is not altogether a cure, since the positive effects were reversed when stimulation was turned off, but could then be returned when resumed. But Dr. Lazamo says he's encouraged.

"So far, the longest follow-up is about a year-and-a-half and the results are sustained. So patients have improved with their depression quite significantly... It's quite a striking result in this population of patients," he told Canada AM.

"Our next goal is more patients and also to introduce this surgery to other centres in Canada and throughout the world to see whether, indeed, the results are reproducible and whether we can define who should be operated, who can benefit from this type of surgery."

The study was a collaboration of scientists from The Rotman Research Institute at Baycrest Centre for Geriatric Care, the Division of Neurosurgery at Toronto Western Hospital, and the departments of Psychiatry, all affiliated with University of Toronto.

It's published in the March 3 issue of Neuron.

With files from CTV's Avis Favaro

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