Procedure aims to ease symptoms in patients with treatment-resistant depression

TORONTO – For the last seven years, Sky Zazlov has been fighting the demon of major depressive disorder — and none of the numerous medications, myriad types of therapy or other interventions she has tried have been able to lift the black cloud of despair that has enveloped her life.

“It affects hygiene, sleep, diet, emotions,” Zazlov, 40, said of the severe treatment-resistant depression she developed in 2011.

“It affects everything, how I interact with my family, whether I’m able to keep friendships, whether or not I can get out of bed and wash my hair and brush my teeth,” said the mother of a 12-year-old boy, who is no longer able to work as a 911 dispatcher in Toronto.

“You feel numb sometimes and empty a lot of the time. There’s not a lot of interest in doing anything or seeing anybody or talking to anyone.”

The symptoms she describes are classic hallmarks of major depression, which affects about a quarter of the Canadian population at some point in life. Almost 14 per cent of people will suffer recurrent bouts of severe depression; among those, about one in 10 will fail to respond to at least three standard antidepressants and be deemed treatment-resistant.

It is a story Zazlov knows all to well.

“Nothing has worked well, nothing has even worked OK up to this point.”

So in desperation, Zazlov agreed to take part in a six-patient clinical trial of a cutting-edge procedure that uses ultrasound beams directed into the brain to alter a pathway known to be at least in part responsible for such psychiatric conditions as depression, obsessive-compulsive disorder (OCD) and post-traumatic stress disorder.

Early Tuesday morning, she became the third patient with intractable depression to be treated at Sunnybrook Health Sciences Centre with MRI-guided focused ultrasound, a non-invasive procedure that sends more than 1,000 beams through the skull to a tiny target in each hemisphere of the brain.

Her head shaved and fitted with a halo-like helmet, Zazlov was placed in an MRI scanner, which transmitted images of her brain to computer screens in an adjacent room. Using those images, doctors were able to pinpoint the four- to five-millimetre areas of her brain and precisely deliver the ultrasound beams.

Those focused beams create a lesion in the region known as the anterior limb of the internal capsule — medical speak for a kind of circuit or information highway that connects the frontal lobes to emotional centres deeper within the brain, and which is implicated in depression and other mood disorders when its function goes awry.

The idea is to “disrupt the activity in a circuit that’s not functioning properly, to effectively reset the activity of that circuit,” said Dr. Nir Lipsman, principal investigator of the trial, the first in North America to use focused ultrasound to try to overcome treatment-resistant depression.

The beauty of the procedure is that it’s non-invasive, said Lipsman, a neurosurgeon who heads Sunnybrook’s Centre for Neuromodulation.

MRI-guided focused ultrasound doesn’t require holes to be drilled in the skull or a probe passed through the brain, which is the case with such surgeries as deep-brain stimulation, another technique that’s been used to alter the pathway and mediate depression and OCD, for instance.

“Now we can generate the same lesion under real-time image guidance without making an incision,” he said.

The next challenge is to see if the procedure will be effective — something that won’t be known for at least several months, said Dr. Anthony Levitt, director of the hospital’s brain sciences program and a trial co-investigator.

“What I anticipate us seeing in the earliest stages is some change in mood, not necessarily positive or consistent,” he said of Zazlov and the other trial participants.

The patients won’t “necessarily feel wonderful and fabulous and recovered … but in that first two months you can see a variety of changes, just evidence that we have tampered with the mood-regulating system. It hasn’t yet adapted itself, it hasn’t come to a settled place, which takes two to six months or more.”

Zazlov, who admitted to being apprehensive before undergoing the hours-long procedure, said she enrolled in the trial because she felt she had nothing to lose, even if “they don’t know if it’s going to work.”

“I’ve done so many trials of medications, different classes of medications,” she said, following up with a lengthy list of therapies, from individual and group counselling to cognitive processing therapy for trauma, to many rounds of repetitive transcranial magnetic stimulation, in which magnetic pulses are passed through the skull to specific regions of the brain.

Some showed promise but then side-effects would set in and it would become unbearable, she said.

“I’m not looking for a magic pill, I’m not looking for a magic bullet … I would like to think that this has the potential to make me somewhat OK, Zazlov said of the ultrasound procedure.

“I’m hoping that I can have a day where I can get out of bed and I can have a day where I can not feel so hopeless and feel that despair — it’s brutal.

“I’d like,” she said pausing with a sigh “to be able to live.”

— Follow @SherylUbelacker on Twitter.