Ethical issues raised around deep brain stimulation (DBS) research

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Researchers grap­ple with the ethics of test­ing brain implants (Sci­ence):

“In 2003, neu­rol­o­gist Helen May­berg of Emory Uni­ver­si­ty in Atlanta began to test a bold, exper­i­men­tal treat­ment for peo­ple with severe depres­sion, which involved implant­i­ng met­al elec­trodes deep in the brain in a region called area 25. The ini­tial data were promis­ing; even­tu­al­ly, they con­vinced a device com­pa­ny, St. Jude Med­ical in Saint Paul, to spon­sor a 200-per­son clin­i­cal tri­al dubbed BROADEN.

This month, how­ev­er, Lancet Psy­chi­a­try report­ed the first pub­lished data on the trial’s fail­ure. The study stopped recruit­ing par­tic­i­pants in 2012, after a 6‑month study in 90 peo­ple failed to show sta­tis­ti­cal­ly sig­nif­i­cant improve­ments between those receiv­ing active stim­u­la­tion and a con­trol group, in which the device was implant­ed but switched off.

Although that deci­sion was “game over” for BROADEN, the sto­ry wasn’t fin­ished for some 44 patients who asked to keep the implants in their brains, and the clin­i­cians respon­si­ble for their long-term care,  May­berg explained last week to col­leagues at a meet­ing on the eth­i­cal dilem­mas of brain stim­u­la­tion research at the Nation­al Insti­tutes of Health (NIH) in Bethes­da, Maryland…A forth­com­ing report from the meet­ing will also exam­ine oth­er eth­i­cal issues researchers might need to con­sid­er, includ­ing the large­ly unknown, long-term effects of stim­u­la­tion on the brain, and how to obtain prop­er con­sent from participants.”

The Study

Sub­cal­los­al cin­gu­late deep brain stim­u­la­tion for treat­ment-resis­tant depres­sion: a mul­ti­site, ran­domised, sham-con­trolled tri­al (Lancet Psy­chi­a­try). From the abstract:

  • Back­ground: Deep brain stim­u­la­tion (DBS) of the sub­cal­los­al cin­gu­late white mat­ter has shown promise as an inter­ven­tion for patients with chron­ic, unremit­ting depres­sion. To test the safe­ty and effi­ca­cy of DBS for treat­ment-resis­tant depres­sion, a prospec­tive, ran­domised, sham-con­trolled tri­al was conducted.
  • Find­ings: …90 par­tic­i­pants were ran­dom­ly assigned to active (n=60) or sham (n=30) stim­u­la­tion between April 10, 2008, and Nov 21, 2012. Both groups showed improve­ment, but there was no sta­tis­ti­cal­ly sig­nif­i­cant dif­fer­ence in response dur­ing the dou­ble-blind, sham-con­trolled phase (12 [20%] patients in the stim­u­la­tion group vs five [17%] patients in the con­trol group). 28 patients expe­ri­enced 40 seri­ous adverse events; eight of these (in sev­en patients) were deemed to be relat­ed to the study device or surgery.
  • Inter­pre­ta­tion: This study con­firmed the safe­ty and fea­si­bil­i­ty of sub­cal­los­al cin­gu­late DBS as a treat­ment for treat­ment-resis­tant depres­sion but did not show sta­tis­ti­cal­ly sig­nif­i­cant anti­de­pres­sant effi­ca­cy in a 6‑month dou­ble-blind, sham-con­trolled tri­al. Future stud­ies are need­ed to inves­ti­gate fac­tors such as clin­i­cal fea­tures or elec­trode place­ment that might improve efficacy.

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