Severely depressed patients who do not respond to conventional therapy may be helped by deep brain stimulation (DBS), according to the most-extensive study to date of the experimental procedure.
In a clinical trial in Toronto, Canada, 12 out of 20 patients who had stimulating electrodes placed in a brain area called the subcallosal cingulated gyrus showed significant improvement in their depression, with seven of them going into full remission.
The benefits lasted at least a year, according to the results published this week in the journal Biological Psychiatry. Patients in the study had failed to respond to cognitive therapy, antidepressant drugs and electroconvulsant therapy.
Lasting effect
The research team published results of DBS on their first six patients in 20052. Four of those patients responded well, and were still showing significant improvement after the trial finished six months later. The new research represents the largest trial on DBS for depression to follow patients for a full year.
“It is a remarkable that so many patients got well and stayed well,” says Helen Mayberg, now at Emory University, Atlanta, Georgia, who helped to develop the therapy.
“Brain surgery is not like getting your nails done, so it is important to try to find out who will benefit.”
“Some patients had to face personal traumas during this period, such as deaths and bankruptcy, but handled them normally — they had a normal dynamic range of feeling,” says neurosurgeon Andres Lozano, of the University of Toronto, who led the study.
Advanced Neuromodulation Systems, a company based in Piano, Texas, that makes DBS electrodes, is now sponsoring a double-blind, controlled phase III trial on up to 200 patients at three centres in the United States.
Participants in the study, called BROADEN (Brodmann Area 25 Deep Brain Neuromodulation), will have DBS devices implanted, targeting the same part of the brain as the Canadian study. Half of the devices will be switched on immediately after surgery, while the other half will wait for six months before being stimulated. Neither the patients nor the scientists and clinicians will know who is switched on at any particular time. The study is expected to take several years to complete.
More than a manicure
“In the meantime we need to know why some of the patients don’t respond at all,” says Mayberg. “Are we missing the target, or are there different subtypes of the disease?” Her team is now trying to find out how to identify those who will respond to DBS, and those who won’t. “Brain surgery is not like getting your nails done, so it is important to try to find out who will benefit.”
Other centres in Germany, Belgium and the Cleveland Clinic in Ohio are also doing DBS trials in depression, but they use slightly different targets in the brain. Neurologists think that the therapy works by activating or damping down particular brain circuits. At the moment, no-one knows which of the targets within these circuits will eventually prove to be the most optimal. “It’s important to have different approaches during these early days of the therapy,” says Mayberg.
The German study, for example, uses the nucleus accumbens. Psychiatrist Thomas Schlaepfer of the University of Bonn says that most of the ten patients studied by the team so far are responding well. “Our patients have been selected from the worst of the worst — people who have been continually depressed for twenty years or more,” he says. “For a psychiatrist it is amazing to see that many of the patients have no symptoms at all any more — although two showed no response at all.”
All Schlaepfer's responders have become very motivated to take up activities instead of lying in bed, he says. The centres are also investigating the value of DBS in other psychiatric disturbances, such as obsessive compulsive disorder and addiction.