Deep Brain Stimulation: New Promise in Alzheimer Disease and Depression?: Page 3 of 4

Deep Brain Stimulation: New Promise in Alzheimer Disease and Depression?: Page 3 of 4

Treatment-resistant depression

DBS has been studied in a small number of clinical trials to treat patients with TRD.

Estimates are that 10% of all depressed patients will become resistant to available treatments, including ECT, so “new options are needed,” Mayberg told Psychiatric Times.

Based on preliminary observations that the subgenual cingulate region (Brodmann area 25 [BA25]) of the brain is metabolically overactive in TRD, Mayberg and colleagues8 in Toronto studied whether DBS to modulate BA25 could reduce the elevated activity and produce clinical benefit for 6 patients with refractory depression. In a study supported by a NARSAD grant, chronic stimulation of white matter tracts adjacent to the subgenual cingulate gyrus was associated with “a striking and sustained remission of depression in 4 of 6 patients” at the end of 6 months, without changes in concurrent medications.

Following the original study, the Toronto team expanded the sample to 20 patients and reported on 12-month outcomes.9 The response rate was 60% (with response defined as a decrease of 50% or greater in total score on the 17-item Hamilton Depression Rating Scale [HAM-D]) and the remission rate was 30% (with remission defined as a HAM-D score of 7 or less).

In 2011, the researchers reported on the extended follow-up of the patients with data from 3 to 6 years after implantation.10 “The cumulative duration of follow-up was 70 patient years,” Giacobbe said. The percentage of patients who responded was 62.5% after 1 year, 46.2% after 2 years, 75% after 3 years, and 64.3% at the last follow-up visit. More than one-third of patients were in remission at year 3 and at last follow-up.

“We also looked at their quality of life,” said Giacobbe. “Not only their mental health quality of life, but their physical well-being, such as vitality and energy, seemed to improve over time.”

Three of the 20 died—1 of cancer; 1 a likely suicide; and 1 a sudden unexplained death, which was considered a possible suicide.

“We have to be extremely vigilant, because this is a group that has been extremely depressed for a very long time. Even 5 to 6 years later, they still need active psychiatric and neurosurgical follow-up,” Giacobbe said.

At the UHN, he added, psychotherapy is offered after DBS. Patients seem to benefit more from post-DBS psychotherapy than pre-DBS psychotherapy. Many patients, he said, feel their “cognitive cloudiness” is lifting and they are no longer actively depressed, so they want to re-enter psychotherapy to sort out job issues, inter-personal relationships, and other difficulties.

In a pilot study sponsored by St Jude Medical, Lozano, Giacobbe, and several others conducted a prospective open-label trial of subcallosal cingulate DBS for 12 months in patients with TRD.11 The Canadian study involved 21 patients at 3 centers—Vancouver, Montreal, and Toronto. Overall, at 6 months, 48% of the patients responded (50% reduction in the 17-item HAM-D), and at 12 months, 29% responded. Published this year, the study results demonstrated that clinical effects of DBS for TRD are reproducible across centers, Giacobbe said.


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