Persistence pays off: After 8‑year follow-up, study finds robust and sustained antidepressant response to deep brain stimulation (DBS)

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Long-Term Fol­low-Up Data Shows Deep Brain Stim­u­la­tion Is an Effec­tive Treat­ment for Treat­ment-Resis­tant Depres­sion (Mount Sinai press release):

“A study pub­lished online on Fri­day, Octo­ber 4, in The Amer­i­can Jour­nal of Psy­chi­a­try found that deep brain stim­u­la­tion (DBS) of an area in the brain called the sub­cal­los­al cin­gu­late (SCC) pro­vides a robust anti­de­pres­sant effect that is sus­tained over a long peri­od of time in patients with treat­ment-resis­tant depres­sion—the most severe­ly depressed patients who have not respond­ed to oth­er treatments.

The long-term data pre­sent­ed in this study, con­duct­ed at Emory Uni­ver­si­ty and led by Helen S. May­berg, MD, now Pro­fes­sor of Neu­rol­o­gy, Neu­ro­surgery, Psy­chi­a­try, and Neu­ro­science, and Found­ing Direc­tor of the Nash Fam­i­ly Cen­ter for Advanced Cir­cuit Ther­a­peu­tics at the Icahn School of Med­i­cine at Mount Sinai, val­i­dates ear­li­er work con­duct­ed by the research team and lays the foun­da­tion for addi­tion­al stud­ies to refine and opti­mize DBS for these patients.

Deep brain stim­u­la­tion, cur­rent­ly approved by the U.S. Food and Drug Admin­is­tra­tion to treat essen­tial tremor, Parkinson’s dis­ease, epilep­sy, and obses­sive-com­pul­sive dis­or­der, is a neu­ro­sur­gi­cal pro­ce­dure involv­ing the place­ment of a neu­rostim­u­la­tor (some­times referred to as a “brain pace­mak­er”), which sends high-fre­quen­cy elec­tri­cal impuls­es through implant­ed elec­trodes deep in the brain to spe­cif­ic brain areas respon­si­ble for the symp­toms of each disorder.

Dr. May­berg led the first tri­al of DBS of the sub­cal­los­al cin­gu­late white mat­ter, known as Brod­mann Area 25, for treat­ment-resis­tant depres­sion patients in 2005, demon­strat­ing that it could have clin­i­cal ben­e­fit. Sub­se­quent small open-label tri­als pro­duced sim­i­lar­ly favor­able results, yet despite these encour­ag­ing open-label results, a mul­ti-cen­ter, ran­dom­ized tri­al was halt­ed ear­ly due to a lack of sta­tis­ti­cal­ly sig­nif­i­cant anti­de­pres­sant response at the des­ig­nat­ed, six-month a pri­ori time point.

“Despite the fact that larg­er tri­als were halt­ed ear­ly, what my col­leagues and I were see­ing as we con­tin­ued to fol­low patients from our ini­tial tri­als was that over time, they were get­ting bet­ter and not only that, they were stay­ing bet­ter. So we stayed the course,” says Dr. May­berg. “Over eight years of obser­va­tion, most of our study par­tic­i­pants expe­ri­enced an anti­de­pres­sant response to the deep brain stim­u­la­tion of Area 25 that was robust and sus­tained. Giv­en that patients with treat­ment-resis­tant depres­sion are high­ly sus­cep­ti­ble to recur­rent depres­sive episodes, the abil­i­ty of DBS to sup­port long-term main­te­nance of an anti­de­pres­sant response and pre­ven­tion of relapse is a treat­ment advance that can mean the dif­fer­ence between get­ting on with your life or always look­ing over your shoul­der for your next debil­i­tat­ing depres­sive episode.”

The Study:

Long-Term Out­comes of Sub­cal­los­al Cin­gu­late Deep Brain Stim­u­la­tion for Treat­ment-Resis­tant Depres­sion (Amer­i­can Jour­nal of Psy­chi­a­try). From the abstract:

• Objec­tive: Deep brain stim­u­la­tion of the sub­cal­los­al cin­gu­late (SCC DBS) has been stud­ied as a poten­tial treat­ment for severe and refrac­to­ry major depres­sive dis­or­der since 2005. The authors used an open-label, long-term fol­low-up design to exam­ine par­tic­i­pants enrolled in a clin­i­cal tri­al of SCC DBS for treat­ment-resis­tant depression.
• Meth­ods: Long-term out­come data were col­lect­ed for 28 patients (20 with major depres­sive dis­or­der and sev­en with bipo­lar II dis­or­der; one patient in the major depres­sion sub­group was lat­er reclas­si­fied as hav­ing bipo­lar II dis­or­der) receiv­ing SCC DBS for 4–8 years.
• Results: Response and remis­sion rates were main­tained at 50% and 30%, respec­tive­ly, through years 2–8 of the fol­low-up peri­od. Three-quar­ters of all par­tic­i­pants met the treat­ment-response cri­te­ri­on for more than half of their dura­tion of par­tic­i­pa­tion in the study, with 21% of all patients demon­strat­ing con­tin­u­ous response to treat­ment from the first year onward. Of 28 par­tic­i­pants, 14 com­plet­ed ?8 years of fol­low-up, 11 com­plet­ed 4 years, and three dropped out before 8 years. The pro­ce­dure itself was gen­er­al­ly safe and well tol­er­at­ed, and there were no side effects of acute or chron­ic stim­u­la­tion. The rate of med­ical or sur­gi­cal com­pli­ca­tions was con­sis­tent with the rate observed in stud­ies of DBS for oth­er indi­ca­tions. There were no suicides.
• Con­clu­sions: In >8 years of obser­va­tion, most par­tic­i­pants expe­ri­enced a robust and sus­tained anti­de­pres­sant response to SCC DBS.

News in Context:

• Eth­i­cal issues raised around deep brain stim­u­la­tion (DBS) research
• Clos­ing the Cir­cuit: Helen Mayberg’s research could rev­o­lu­tion­ize depres­sion treatment