A Randomized Sham-Controlled Trial of Deep Brain Stimulation of the Ventral Capsule/Ventral Striatum for Chronic Treatment-Resistant Depression

Darin D. Dougherty, Ali R. Rezai, Linda L. Carpenter, Robert H. Howland, Mahendra T. Bhati, John P. O'Reardon, Emad N. Eskandar, Gordon H. Baltuch, Andre D. Machado, Douglas Kondziolka, Cristina Cusin, Karleyton C. Evans, Lawrence H. Price, Karen Jacobs, Mayur Pandya, Timothey Denko, Audrey R. Tyrka, Tim Brelje, Thilo Deckersbach, Cynthia KubuDonald A. Malone

Research output: Contribution to journalArticle

170 Citations (Scopus)

Abstract

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. Conclusion 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.

Original languageEnglish (US)
Pages (from-to)240-248
Number of pages9
JournalBiological Psychiatry
Volume78
Issue number4
DOIs
StatePublished - Aug 15 2015
Externally publishedYes

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Treatment-Resistant Depressive Disorder
Deep Brain Stimulation
Capsules
Randomized Controlled Trials
Depression
Therapeutics
Outcome Assessment (Health Care)
Ventral Striatum
Control Groups

Keywords

  • DBS
  • Deep brain stimulation
  • Major depression
  • TRD
  • Treatment resistant depression
  • Ventral capsule/ventral striatum

ASJC Scopus subject areas

  • Biological Psychiatry

Cite this

Dougherty, D. D., Rezai, A. R., Carpenter, L. L., Howland, R. H., Bhati, M. T., O'Reardon, J. P., ... Malone, D. A. (2015). A Randomized Sham-Controlled Trial of Deep Brain Stimulation of the Ventral Capsule/Ventral Striatum for Chronic Treatment-Resistant Depression. Biological Psychiatry, 78(4), 240-248. https://doi.org/10.1016/j.biopsych.2014.11.023

A Randomized Sham-Controlled Trial of Deep Brain Stimulation of the Ventral Capsule/Ventral Striatum for Chronic Treatment-Resistant Depression. / Dougherty, Darin D.; Rezai, Ali R.; Carpenter, Linda L.; Howland, Robert H.; Bhati, Mahendra T.; O'Reardon, John P.; Eskandar, Emad N.; Baltuch, Gordon H.; Machado, Andre D.; Kondziolka, Douglas; Cusin, Cristina; Evans, Karleyton C.; Price, Lawrence H.; Jacobs, Karen; Pandya, Mayur; Denko, Timothey; Tyrka, Audrey R.; Brelje, Tim; Deckersbach, Thilo; Kubu, Cynthia; Malone, Donald A.

In: Biological Psychiatry, Vol. 78, No. 4, 15.08.2015, p. 240-248.

Research output: Contribution to journalArticle

Dougherty, DD, Rezai, AR, Carpenter, LL, Howland, RH, Bhati, MT, O'Reardon, JP, Eskandar, EN, Baltuch, GH, Machado, AD, Kondziolka, D, Cusin, C, Evans, KC, Price, LH, Jacobs, K, Pandya, M, Denko, T, Tyrka, AR, Brelje, T, Deckersbach, T, Kubu, C & Malone, DA 2015, 'A Randomized Sham-Controlled Trial of Deep Brain Stimulation of the Ventral Capsule/Ventral Striatum for Chronic Treatment-Resistant Depression', Biological Psychiatry, vol. 78, no. 4, pp. 240-248. https://doi.org/10.1016/j.biopsych.2014.11.023
Dougherty, Darin D. ; Rezai, Ali R. ; Carpenter, Linda L. ; Howland, Robert H. ; Bhati, Mahendra T. ; O'Reardon, John P. ; Eskandar, Emad N. ; Baltuch, Gordon H. ; Machado, Andre D. ; Kondziolka, Douglas ; Cusin, Cristina ; Evans, Karleyton C. ; Price, Lawrence H. ; Jacobs, Karen ; Pandya, Mayur ; Denko, Timothey ; Tyrka, Audrey R. ; Brelje, Tim ; Deckersbach, Thilo ; Kubu, Cynthia ; Malone, Donald A. / A Randomized Sham-Controlled Trial of Deep Brain Stimulation of the Ventral Capsule/Ventral Striatum for Chronic Treatment-Resistant Depression. In: Biological Psychiatry. 2015 ; Vol. 78, No. 4. pp. 240-248.
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abstract = "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-{\AA}sberg 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-{\AA}sberg 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. Conclusion 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.",
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AU - Dougherty, Darin D.

AU - Rezai, Ali R.

AU - Carpenter, Linda L.

AU - Howland, Robert H.

AU - Bhati, Mahendra T.

AU - O'Reardon, John P.

AU - Eskandar, Emad N.

AU - Baltuch, Gordon H.

AU - Machado, Andre D.

AU - Kondziolka, Douglas

AU - Cusin, Cristina

AU - Evans, Karleyton C.

AU - Price, Lawrence H.

AU - Jacobs, Karen

AU - Pandya, Mayur

AU - Denko, Timothey

AU - Tyrka, Audrey R.

AU - Brelje, Tim

AU - Deckersbach, Thilo

AU - Kubu, Cynthia

AU - Malone, Donald A.

PY - 2015/8/15

Y1 - 2015/8/15

N2 - 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. Conclusion 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.

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