Deep-brain stimulation involves implanting electrodes in parts of the brain. Credit: MEDICAL BODY SCANS/SPL

Depressed patients who are resistant to other therapies can be helped long term by deep-brain stimulation. The effects can still be seen six years after implanting stimulating electrodes deep inside the brain, according to a follow-up of patients published online in the American Journal of Psychiatry.

The study was carried out by a team led by psychiatrist Sidney Kennedy and neurosurgeon Andres Lozano at the University Health Network in Toronto, Canada.

They show that, within a year of implantation, depression lifted in 12 of 20 patients — and that the benefits were sustained for up to six years. But two of the patients died by presumed suicide.

The good news is that those who showed an early response to deep-brain stimulation maintained that response, says Kennedy. "However the suspected suicides indicate that we have not been able to prevent the course of illness," he adds.

According to Thomas Schläpfer, a psychiatrist at the University of Bonn, Germany, the study shows that deep-brain stimulation does actually seem to modify the disease, something that no other treatment has done. "Medication studies in depression always show patients relapsing, even if they respond at first — but responders in this study did not relapse." In the paper, response is defined as a decrease by 50% or more in scores on the Hamilton rating scale for depression.

Improvement, not cure

Patients seemingly helped by anti-depression medication also sometimes attempt suicide, says Schläpfer. "Improvements in symptoms of depression doesn't mean a patient is no longer depressed at all."

The 20 patients in the deep-brain stimulation trial were at particularly high risk of suicide, having failed to respond to four different treatments, including psychotherapy, drug therapy or electroconvulsant therapy. On average, they had been seriously depressed for 20 years. "Between 15 and 30% of such treatment-resistant patients commit suicide," says Kennedy.

"But most of those who responded to the deep-brain stimulation were well enough to embark on paid employment," he adds. Responders began to undertake and enjoy social interactions and reported having a better quality of life. "When some patients complained that they had lost the effect, we found that the batteries feeding their electrodes had simply run down," says Kennedy. "The effect came back shortly after we replaced the batteries."

Schläpfer has conducted a long-term study of 13 treatment-resistant patients together with neurosurgeon Volker Sturm from the University of Cologne, Germany, which targeted a slightly different site in the brain. It is not yet published, but the results are similar, he says. One patient committed suicide, but six responded and continue to respond.

Both of these studies are pilots and were not placebo-controlled. Double-blind, placebo-controlled trials involving 40 patients are being launched by Health Canada. In half the patients, newly implanted electrodes will remain switched off for the first few months, with neither patient nor psychiatrist knowing whether electrodes are on or off in individual patients.

Two electrode manufacturers, Medtronic, headquartered in Minneapolis, Minnesota, and St Jude Medical of Little Canada, Minnesota, are planning to begin similar trials in the United States.