November 08, 2019
By Will Boggs MD
NEW YORK (Reuters Health) - Subcallosal cingulate deep brain stimulation (DBS) provides long-term relief in patients with treatment-resistant depression, according to results from a single-arm clinical trial.
"The patients who participated in this study are all at high risk of future depressive episodes and most had the experience in the past of responding well to other treatments (like medication) that then stopped working," said Dr. Andrea L. Crowell of Emory University School of Medicine in Atlanta.
"That around one out of five of our participants got better and stayed better continuously for years really speaks to the power and potential of DBS as a treatment for severe treatment-resistant depression," she told Reuters Health by email.
Several open-label studies have demonstrated the effectiveness of subcallosal cingulate (SCC) DBS as a treatment for severe and highly refractory major depression, including one study that showed a sustained treatment response up to six years following implantation. But a multicenter randomized sham-controlled trial was halted early because of a lack of statistically significant antidepressant response to SCC DBS after six months.
In the current single-arm study, Dr. Crowell's team report long-term follow-up data (up to eight years) for 28 patients who received SCC DBS at their center for treatment-resistant depression or, in less than a third of the cases, bipolar 2 disorder.
Twenty patients (71%) showed consistent improvements of at least 25% from baseline depression severity ratings throughout the study, including 18 patients (64%) who showed improvements of at least 50% from baseline for the majority of their years of participation in the study.
Thirteen long-term responders demonstrated a continuous antidepressant response after first reaching study response criteria (at least a 50% decrease from baseline in the Hamilton Depression Rating Scale, or HAM-D), and six participants (21%) maintained at least a 50% improvement continuously since their first year of participation, the researchers report in the American Journal of Psychiatry, online October 4.
In the subgroup of eight patients with bipolar 2, five showed a favorable response pattern and three exhibited limited antidepressant responses over time.
There were 19 serious adverse events related to the implantation surgery and 15 device-related serious adverse events, primarily as a result of device malfunction.
The average life of the non-rechargeable implantable pulse generator was 16.5 months, and each participant underwent two to six implantable pulse generator replacement surgeries during follow-up.
"At present, SCC DBS is still an experimental treatment, not approved by the FDA to treat depression," Dr. Crowell said. "As there are few therapeutic options for patients with treatment-resistant depression, especially those who have failed electroconvulsive therapy (ECT) or cannot tolerate that treatment, we hope that our findings encourage the field to continue to pursue clinical trials of SCC DBS."
"Funding agencies, industry, and the public should not be disappointed by some early failed trials in this field," Dr. Crowell said. "Given the impressive efficacy and sustainability of this intervention, future research can take advantage of ongoing work to optimize surgical methods, patient selection, and clinical trial design in order to more fully capture the impact of this treatment."
Dr. Mahendra T. Bhati, chief of interventional neuropsychiatry at Stanford University School of Medicine, in California, studies treatment-resistant depression and has also researched DBS treatment. He told Reuters Health by email, "The sustained response seen with DBS is something not seen with other treatments for depression in this population of treatment-resistant patients."
"DBS is relatively safe, and there is a growing body of evidence showing the benefit for DBS when used to treat depression and obsessive-compulsive disorder (OCD)," said Dr. Bhati, who was not involved in the study. "DBS provides another option in the growing number of interventional psychiatric treatments, and interventional psychiatric treatments have the potential to revolutionize and advance an understanding of the brain leading to improved psychiatric treatments."
The study did not have commercial funding, but the devices were donated by St. Jude Medical, now Abbott. Three of Dr. Crowell's coauthors have financial ties to the company.
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