“It may be that stimulation of the nucleus accumbens altered the reward circuitry in the brain such that it turned down the volume on the pleasurable craving that patients with alcohol use disorder feel when they see or are around alcoholic beverages,” says Nir Lipsman, the study’s principal investigator and a neurosurgeon at Sunnybrook Health Sciences Centre.
Lipsman hopes to expand the trial in order to verify his findings. He is also keen to determine brain signals associated with cravings for alcohol so stimulation may only be required at specific times.
Many psychiatric disorders may eventually be treated by DBS, according to scientists working in this space. For example, Sheth’s September review in the Journal of Neurology, Neurosurgery, and PsychiatDr. ry reviewed 34 DBS studies to help with obsessive compulsive disorder. It was successful for 66 per cent of 352 patients.
Scaling the therapy can be difficult. It is difficult to reproduce some psychiatric disorders in mice, like anorexia or bulimia. It is difficult for human research to proceed because of this. Because doctors could target various parts of the brain depending upon the condition, regulators want to ensure that the procedure is safe before allowing larger trials in humans. “It’s important to appreciate that this started with very well controlled and planned mouse studies,” Halpern says. “We didn’t just go straight to doing surgery in the human brain.”
The trials are also expensive—costing researchers around $100,000 per patient—and require complicated surgeries that carry risks for participants. After surgery, infections can occur at the electrode site. An improperly placed electrode or stimulation that is too frequent can result in changes of mood. After receiving the implanted brains, one of the Toronto patients was more angry. Once researchers reduced the voltage, the patient’s mood stabilized.) Because of these challenges, studies can be small and lacking a placebo group making it hard to draw broad conclusions about the effectiveness.
They also need to take place over long periods so that researchers can accurately capture the effects of stimulation—but it can be hard to justify a long trial if patients don’t seem to be getting better. Two high-profile DBS trials were unsuccessful in demonstrating improvement for depression. In the smaller of the two studies, researchers measured patients’ response rates after just 16 weeks. St. Jude Medical was the sponsor of the smaller trial. An interim analysis showed that there wasn’t any benefit over a control group receiving a sham device.
Helen Mayberg was a Mount Sinai Health System neurologist in New York. Helen pioneered DBS and worked as a consultant for the St. Jude study. Helen believes the premature termination of the trial was a mistake. Research over the last decade has shown that stimulation of the subcallosal Cingulate (also known as area 25) can relieve severe depression. It plays an important role in the regulation of appetite, self-esteem and sadness processing. Some patients suffering from severe depression have been shown to be hyperactive. But subsequent research by Mayberg and her colleagues found that many of the trial’s patients who didn’t initially respond to the therapy eventually showed improvement.
The device placement also affects the effectiveness of therapy, according to her. She recalls one of her patients who wasn’t improving after six months of stimulation. Upon examination, the electrode wasn’t inserted deep enough. When it was moved to the correct spot, the person’s symptoms started improving. “We think that proves that location explains most of your variance in outcomes,” Mayberg says.
Abbott Medical is getting ready for the next trial after it acquired St. Jude Medical. Abbott’s system was granted breakthrough device designation by the FDA in July as a treatment for depression.
There are still questions about who will be able to benefit from DBS. Mayberg, along with her colleagues, have collected brain recordings of severely depressed patients. They believe that they have identified a specific signature which indicates who may respond to DBS. Researchers are trying to find signals that could be used for other mental disorders. “There’s simultaneously this amazing promise, but so far an unrealized potential,” says George.