A Randomized Sham-Controlled Trial of Deep Brain Stimulation of the Ventral Capsule/Ventral Striatum for Chronic Treatment-Resistant Depression.
BACKGROUND
Multiple open-label trials of deep brain stimulation (DBS) for treatment-resistant depression (TRD), including those targeting the ventral capsule/ventral striatum target, have shown encouraging response rates. However, no randomized controlled trials of DBS for TRD have been published.


METHODS
Thirty patients with TRD participated in a sham-controlled trial of DBS at the ventral capsule/ventral striatum target for TRD. Patients were randomized to active versus sham DBS treatment in a blinded fashion for 16 weeks, followed by an open-label continuation phase. The primary outcome measure was response, defined as a 50% or greater improvement on the Montgomery-Åsberg Depression Rating Scale from baseline.


RESULTS
There was no significant difference in response rates between the active (3 of 15 subjects; 20%) and control (2 of 14 subjects; 14.3%) treatment arms and no significant difference between change in Montgomery-Åsberg Depression Rating Scale scores as a continuous measure upon completion of the 16-week controlled phase of the trial. The response rates at 12, 18, and 24 months during the open-label continuation phase were 20%, 26.7%, and 23.3%, respectively.


CONCLUSIONS
The results of this first randomized controlled study of DBS for the treatment of TRD did not demonstrate a significant difference in response rates between the active and control groups at the end of the 16-week controlled phase. However, a range of 20% to 26.7% of patients did achieve response at any time during the open-label continuation phase. Future studies, perhaps utilizing alternative study designs and stimulation parameters, are needed.
Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts. Electronic address: ddougherty@partners.org.
Darin D
DD
Dougherty
Department of Psychiatry and Psychology, Cleveland Clinic, Cleveland, Ohio.
Ali R
AR
Rezai
Butler Hospital, Alpert Medical School of Brown University, Providence, Rhode Island.
Linda L
LL
Carpenter
Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center, Pittsburgh.
Robert H
RH
Howland
Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
Mahendra T
MT
Bhati
Department of Psychiatry, University of Medicine and Dentistry of New Jersey School of Osteopathic Medicine, Stratford, New Jersey.
John P
JP
O'Reardon
Department of Neurosurgery, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
Emad N
EN
Eskandar
Department of Neurosurgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
Gordon H
GH
Baltuch
Center for Neurological Restoration, Cleveland Clinic, Cleveland, Ohio.
Andre D
AD
Machado
Department of Neurosurgery, New York University Langone Medical Center, New York University, New York, New York.
Douglas
D
Kondziolka
Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
Cristina
C
Cusin
Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
Karleyton C
KC
Evans
Butler Hospital, Alpert Medical School of Brown University, Providence, Rhode Island.
Lawrence H
LH
Price
Department of Psychiatry and Psychology, Cleveland Clinic, Cleveland, Ohio.
Karen
K
Jacobs
Department of Psychiatry and Psychology, Cleveland Clinic, Cleveland, Ohio.
Mayur
M
Pandya
Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center, Pittsburgh.
Timothey
T
Denko
Butler Hospital, Alpert Medical School of Brown University, Providence, Rhode Island.
Audrey R
AR
Tyrka
Medtronic, Inc, Minneapolis, Minnesota.
Tim
T
Brelje
Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
Thilo
T
Deckersbach
Department of Psychiatry and Psychology, Cleveland Clinic, Cleveland, Ohio.
Cynthia
C
Kubu
Department of Psychiatry and Psychology, Cleveland Clinic, Cleveland, Ohio.
Donald A
DA
Malone
D000328:Adult; D000368:Aged; D002908:Chronic Disease; D046690:Deep Brain Stimulation; D003865:Major Depressive Disorder / Q000628:therapy*; D061218:Depressive Disorder, Treatment-Resistant / Q000628:therapy*; D005260:Female; D006801:Humans; D020772:Internal Capsule / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D011569:Psychiatric Status Rating Scales; D016896:Treatment Outcome; D066328:Ventral Striatum / Q000503:physiopathology*; D055815:Young Adult
DBS; Deep brain stimulation; Major depression; TRD; Treatment resistant depression; Ventral capsule/ventral striatum