When is a new brain treatment ready for the real world? After many trials and much research, the therapy known as deep brain stimulation (DBS) was approved by the FDA to treat Parkinson's disease and essential tremor. There is strong evidence it works as well or better than drugs in some cases of these motor-circuit disorders, as you can see in these "60 Minutes" clips featuring Sybil Guthrie (pt 1 before surgery, part 2 surgery and after). Now DBS is being tried to treat diseases such as obsessive-compulsive disorder, Tourette's, and severe depression. While it is still considered a very experimental treatment for the latter two cases, in 2009, the FDA bypassed its normal procedure to approve the use of DBS for OCD without first requiring the years of research to prove it works on that disorder.
This relatively quick action was praised by doctors and researchers who work with people who have severe OCD. For these patients, there is very little treatment that works, and though their disability can be great, their numbers are too small to entice device makers to spend the money on potentially profitless experimentation. But some in the field have sounded a warning, including Dana Alliance member Helen Mayberg and former Dana grantee Joseph Fins, who with others co-authored a commentary in the journal Health Affairs (abstract only) in February arguing that the FDA's use of its "humanitarian device exemption" was misguided (here's another description of the commentary). Guy McKhann, an Alliance member and the science advisor for our Brain in the News monthly roundup, also argued against the move in his March column.
DBS is brain surgery; opening the skull to insert electrodes deep into the brain and wires that lead down to the chest, where a pacemaker-style device is inserted that controls pulses of electricity through the circuit. While it does not destroy the targeted tissue, and the current can be turned up or down or off if it doesn't work right, it is an invasive procedure that carries risk.
Fins, Mayberg, fellow Alliance member Mahlon DeLong, and others spoke about this and ethical issues of using surgery to treat psychiatric disorders at the annual meeting of the American Association for the Advancement of Science, in Washington, DC, in February. DBS is a "reversible, adjustable form of neuromodulation," DeLong said, and it can have a "dramatic, transformative effect. It's not disease-specific, but circuit-specific."
Benjamin Greenberg, who treats people with severe, intractable OCD, argued that the exemption was warranted. "In the real world, a small subset of 'treatment-resistant' patients get OCD surgery," he said, perhaps 15 people a year. In comparison, around 70,000 people with Parkinson's have had the surgery so far. "This [OCD] population is so small, humanitarian use is the only way they can get access to this treatment." (Even if it was working, he said, one-third of people in his care stopped using the device, some because the battery wears out and insurance won't pay for $1,000 replacement surgery.)
That may be, Fins said, but "now that we have the hint of efficacy and safety, we can no longer classify it as 'great and desperate' need." For that matter, we still don't understand why it works, and whether jolting one area is the same or better than jolting another. Mayberg's research (some funded by the Dana Foundation) has found different brain targets that seem to relieve symptoms of depression as compared with Parkinson's, and Greenberg says they also have "refined the target" in their surgery for OCD. So while the device may work the same, its placement may produce far different effects, Fins argued – it appears to connect or interrupt completely different circuits.
All the panelists at the AAAS meeting did agree that researchers, device makers, and doctors should share their data in a central repository. Fins called on the FDA to require such a repository, which could help doctors see which methods work best and more quickly reject methods and targets that don't work. He also suggested that perhaps the requirements should change: "Most of what we do is handed down from the drug world, but devices aren't drugs." Right now, for example, researchers need to prove the effect is gigantic because the number of patients is so small, as is true for drug research, but "maybe the number issue isn't applicable; maybe we just need to prove it's a successful technique."
The panelists also cautioned that in no case is DBS a cure. Just as with drugs, the effects of the stimulation lessen in Parkinson's patients. The surgery for OCD "gives patients back many, many more hours of their day," Greenberg said, for people whose illness can lead them to take hours just to get dressed. "Giving them more symptom-free time is a tremendous improvement, but it's not a cure."
And people who have spent years debilitated by psychiatric disorders may see their symptoms ease, but their sometimes-troubled lives are the same as they were the day before. As with drugs or any other intervention, they will need therapy, follow-up care, and other services such as job-search help, as many have been too ill to work for a decade or more.
With depression, Mayberg said, "I almost believe that all I'm doing is unsticking you; after that it's up to you." She described a patient who had had the surgery for depression; among many other things the woman had tried cognitive-behavioral therapy before the surgery but it didn't work; when she tried it after surgery, she had more success. Mayberg showed a video of the woman describing the difference as "like night and day." "It made sense up here," she says on the film, pointing to her brain, but after the surgery, "it made sense here in my soul," pointing to her heart. "Because I had a brain that worked."
"These people need rehab, just as a person with a hip repacement needs therapy to learn how to walk before running a marathon," Mayberg said.
DeLong wrote an essay for Cerebrum on using DBS on the mind in 2009; this past week, we published a review of research using DBS to treat Tourette syndrome by freelance writer Christine Ottery. AAAS also did a 12-min podcast with some of the panelists during the annual meeting.