Also testing subcallosal cingulate DBS is the BROADEN (BROdmann Area 25 DEep brain Neuromodulation) study to evaluate the safety and effectiveness of DBS in treatment-resistant severe MDD. This 6-month, blinded, sham-controlled clinical trial sponsored by St Jude Medical is under way at some 20 sites in North America.
At Emory University, Mayberg and colleagues are conducting further studies to examine sub-callosal cingulate efficacy and mechanisms in various subgroups, including unipolar and bipolar depressed patients.
This year, Holtzheimer and colleagues12 reported their first results of a DBS trial that included a 4-week sham stimulation phase; a 24-week, open-label, active-stimulation phase; and an observational follow-up phase.
Performed under a physician-sponsored investigational device exemption and supported by grants from the Dana Foundation, the Stanley Medical Research Institute, and the Woodruff Foundation, the study involved 17 patients, 10 with MDD and 7 with bipolar II who were experiencing depression.
After 2 years of chronic stimulation involving 12 patients, Holtzheimer and colleagues found patient response and remission rates were high (92% response, and 58% remission). In addition, patients who achieved remission did not experience a spontaneous relapse, efficacy was similar for MDD and bipolar II patients, and no patient experienced a hypomanic or manic episode during the study.
Beyond BA25, other brain targets are being evaluated in both open-label DBS trials and controlled clinical trials. These areas include the nucleus accumbens, ventral capsule/ventral striatum, lateral habenula, and anterior thalamic peduncle. DBS trials for depression are also being conducted in Europe.
Like any other brain surgery, DBS includes risk of stroke, hemorrhage, seizure, and infection, according to Mayberg and Giacobbe. There are also risks with general anesthesia and with possible equipment malfunction or breakage.
“DBS surgeons quote about a 5% risk of a serious event occurring during the procedure,” Giacobbe said.
Regarding continued trials of DBS for depression, both Giacobbe and Mayberg remain highly committed and optimistic. For Giacobbe, it’s the possibility of advancing treatment options and being “on the cusp of making some meaningful changes.” For Mayberg, it is “seeing that our research can make a difference” and “seeing patients get their lives back.”