The first patient to be treated for depression using a new form of electric brain stimulation has experienced dramatic and sustained improvement. Much larger trials will be needed to demonstrate the reliability of the technique, but the team responsible hopes it will prove life-changing for people who don't respond to antidepressant drugs.

Deep Brain Stimulation (DBS), where electrodes producing carefully tuned electrical signals are implanted in relevant regions of the brain, has helped some people with treatment-resistant depression. However, success rates for depression have been lower than for some other conditions, such as Parkinson's Disease and epilepsy.

The team from the University of California, San Francisco considered traditional DBS implants too generic, failing to account for variations between individuals. They implanted a patient with DBS electrodes that recognize and respond to brain activity indicating depression, and reported the success in Nature Medicine. 

"This study points the way to a new paradigm that is desperately needed in psychiatry," Professor Andrew Krystal said in a statement. "We've developed a precision-medicine approach that has successfully managed our patient's treatment-resistant depression by identifying and modulating the circuit in her brain that's uniquely associated with her symptoms."

Traditional DBS for depression has two flaws, Krystal argues. Firstly, DBS works by targeting a specific small area of the brain, where the implants are placed. This can work well for conditions where the location of the problem is consistent, but the brain area responsible for depression in one person may be different from that in another.

Secondly, DBS devices produce a constant signal even when the need is not there.

Krystal and co-authors implanted a reactive device in the brain of a 36-year-old patient named Sarah who had suffered major depressive disorder since childhood. They identified a pattern of brainwaves indicating depression and had the device respond only when it detected that pattern. Not only was this successful, Krystal said, but the results were almost instantaneous, in contrast to other treatments that usually take 4-8 weeks to work. Applying current only when needed “Mitigates concerns for neural adaptation, preserves battery life and reduces side effects,” the paper notes.

The paper was written 15 months after the operation, and success had been sustained up to that point.

 

Krystal credits the success to Professor Edward Chang's work exploring depression and anxiety in patients undergoing surgery for epilepsy. Studying epilepsy and depression together led Chang to look at brain regions not previously considered as relevant for stimulation against depression.

"This new study puts nearly all the critical findings of our previous research together into one complete treatment aimed at alleviating depression," Chang said. 

The treatment required electrodes to be placed in two parts of Sarah's brain, one where it could detect the brainwaves indicative of depression, and another where a signal was most effective in counteracting the effects. DBS is not without risks, and needing to place electrodes in separate parts of the brain will presumably increase those, but the rate of complications has fallen dramatically in recent years for traditional DBS as surgeons' experience increases and new methods arise. 

Two other patients have been enrolled to have similar implants, and the team is seeking more to explore the similarities and differences in responses across a meaningful sample, but the approach will remain experimental for a long time.

"In the early few months, the lessening of the depression was so abrupt, and I wasn't sure if it would last," Sarah said. "But it has lasted...those thoughts still come up, but it's just… poof… the cycle stops."