Major depression affects up to eight percent of American adults, darkening every aspect of life: relationships, work, sleep. Treatment usually includes talk therapy and medication, but those don't work for everyone.

One New Jersey resident with persistent, severe depression chose to take a step into the unknown. WHYY's Behavioral Health reporter Maiken Scott followed her progress at every stage of an experimental treatment, and retraces the two-year journey.


It is May of 2009. Tara Aliotta almost has a spring in her step. Her wardrobe is fashionable and bright, as if the cheerful colors could chase away the relentless depression that has darkened her life.

"I knew something was wrong when I was about 11 years old," remembers Aliotta. "I went into my parents' medicine chest and took out a bottle of Valium and had a profound sadness, and wanted to take the whole bottle."

She is in her fifties, and has been hospitalized, institutionalized, tried countless medications and treatments. Nothing has helped. She has always managed to keep a job. But lately, her world keeps getting smaller. Everything feels like an effort, like she is walking through quicksand, said Aliotta. "I used to go to church every Sunday, I used to be able to go to the mall, and past two to three years I haven't been able to do that."

Aliotta's case is a challenge for Dr. John O'Reardon, a wiry psychiatrist who is the lead investigator for a University of Pennsylvania study that is testing a treatment approach called DBS. DBS stands for Deep Brain Stimulation, and involves placing tiny electrodes deep into the brain, and delivering stimulation through those electrodes in key circuits in the brain.

In depressed patients, explains O'Reardon, it's as if the parts of the brain that are responsible for regulating mood have gone on strike. The stimulation is supposed to jolt them into action.

After much trial and error, DBS been successful with Parkinson's patients, but this is the first large-scale study to test if it can help relieve severe depression. The University of Pennsylvania is one of five study sites, and eight of the 30 patients in the trial are here.

O'Reardon is hopeful it might deliver relief to his most severe patients. "It is the cutting edge of what modern neuroscience can do to help patients that otherwise have no other meaningful treatment options at this point," he said.

'I know relief is possibly coming'

The first step for Tara Aliotta is surgery to implant the electrodes. On May 4, 2009, she arrives at Pennsylvania Hospital. Her aging parents are with her. Their daughter's long history of suffering is written on their worried faces. "I think this is my only chance I have left, really," said Aliotta.

In the operating room, brain surgeon Gordon Baltuch inserts the electrodes through two dime-sized holes in Aliotta's skull. Then, a psychiatrist involved in the study conducts tests to check if stimulation has any effect on Aliotta's mood. She is awake just enough to answer.

He asks her questions about how she feels, while changing the settings on the stimulation delivered by the electrodes. Aliotta reports that if zero is the worst mood and ten is not depressed at all she is about a six.

After recovering from the the six-hour procedure, Aliotta enters what's called the "blinded" phase of the study in June 2009. For 16 weeks, the participants won't know if their devices are turned on or not. This is done to control for a placebo effect.

Aliotta is not feeling any better: "I've had some really bad days, really dark days, but I know relief is possibly coming, I'm trying to do the best I can."

'Not a hopeless case'

After 16 weeks of uncertainty and not feeling well, she enters the next phase of the study in October of 2009, and knows that her device is turned on for sure. Then, the stimulation has to be optimized.In one session, psychiatrist Mahendra Bhati tries to find the best settings for the electrodes in Aliotta's brain. As he changes the settings on the electrodes, he has to observe Tara very closely, to get a sense of her mood.

"Typically with Tara I either see agitation or a sense of calm," saaid Bhati. "But in some patients you can see them get flushed, you can see them get lethargic, you can also see them smile spontaneously, I have seen that on one occasion with Tara."

Despite Bhati's best efforts, Aliotta experiences no lasting improvements. She has to move back in with her parents, where conflicts arise. Her father falls ill. During a visit with Dr. O'Reardon in March 2010, she looks exhausted, drawn, and defeated.

Her tireless champion, Dr. O'Reardon gives a pep talk. "You're entirely entitled to feel hopeless, but you are not a hopeless case, medically," O'Reardon said. "You are not a hopeless case, and there's always hope we can find something."

Other study participants are doing better. Ciara, a woman in her thirties, is seeing benefits. "I used to carry around this huge weight on my chest that just hurt all the time," Ciara says, "and it never ever went away, and I feel like that's gone. I talk now. I can actually read a book."

Holding on

Aliotta and her team try different settings, medications. Nothing helps. In early 2011, it's clear DBS is not working for her. The electrodes are shut off. In April she returns to the hospital to have them removed. Once again, her parents are with her, looking still more worried and worn. Tara looks fragile and child-like in her hospital gown. She says she simply doesn't know where to go from here, and admits that she thinks about death all of the time.

Her father, Anthony Aliotta, sums up the grief: "This is a sad day for us today, because it's the culmination of an effort that Tara made, and we see her every day how she suffers."

Tara promises to hold on, for her parents, and for Dr. O'Reardon, who is still trying to find relief for her.

As a whole, the study has shown mixed results for DBS in treating depression. In Philadelphia, four participants got a lot better.  The other four saw no improvement. But O'Reardon says DBS is by no means finished as a tool in treating depression. He says this point doesn't mark an end, it marks the end of the beginning phase. "We have learned a lot, and we want to apply that in future studies, so that we will move along this road positively," said O'Reardon.

O'Reardon says researchers have to now investigate why the approach works for some patients, and not others. In the Philadelphia study, there was a clear difference between how men and women responded to DBS. Also, different placements of electrodes will be tested.

And even though the approach Tara called her "last chance" didn't work for her, she wants the research to move forward: "I would never have anyone say, definitely don't do this. Because, if there's a chance for it to work for someone, take that chance."

As of July 2011, Tara Aliotta remains in treatment with Dr. O'Reardon, even though she is no longer in the study. She is living with her parents.