Paul E Holtzheimer1, Mustafa M Husain2, Sarah H Lisanby3, Stephan F Taylor4, Louis A Whitworth5, Shawn McClintock6, Konstantin V Slavin7, Joshua Berman8, Guy M McKhann9, Parag G Patil10, Barry R Rittberg11, Aviva Abosch12, Ananda K Pandurangi13, Kathryn L Holloway14, Raymond W Lam15, Christopher R Honey16, Joseph S Neimat17, Jaimie M Henderson18, Charles DeBattista19, Anthony J Rothschild20, Julie G Pilitsis21, Randall T Espinoza22, Georgios Petrides23, Alon Y Mogilner24, Keith Matthews25, DeLea Peichel26, Robert E Gross27, Clement Hamani28, Andres M Lozano29, Helen S Mayberg30. 1. Department of Psychiatry and Department of Surgery, Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA. Electronic address: paul.e.holtzheimer@dartmouth.edu. 2. Department of Psychiatry, Neurology and Medicine, University of Texas Southwestern Medical Center at Dallas, Dallas, TX, USA; Department of Psychiatry and Behavioral Science, Duke University School of Medicine, Durham, NC, USA. 3. National Institute of Mental Health, Rockville, MD, USA. 4. Department of Psychiatry, University of Michigan, Ann Arbor, MI, USA. 5. Neurological Surgery, Radiation Oncology, Department of Neurological Surgery, University of Texas Southwestern Medical Center at Dallas, Dallas, TX, USA. 6. Department of Psychiatry, University of Texas Southwestern Medical Center at Dallas, Dallas, TX, USA; Department of Psychiatry and Behavioral Science, Duke University School of Medicine, Durham, NC, USA. 7. Department of Neurosurgery, University of Illinois at Chicago, Chicago, IL, USA. 8. Department of Psychiatry, Division of Experimental Therapeutics, Columbia University College of Physicians & Surgeons, New York, NY, USA. 9. Department of Neurosurgery, Columbia University Medical Center, New York Presbyterian Hospital, New York, NY, USA. 10. Department of Neurosurgery, Neurology, Anesthesiology and Biomedical Engineering, University of Michigan, Ann Arbor, MI, USA. 11. Department of Psychiatry, University of Minnesota, Minneapolis, MN, USA. 12. Department of Neurosurgery and Department of Neurology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA. 13. Department of Psychiatry, Virginia Commonwealth University, Richmond, VA, USA. 14. Department of Neurosurgery, Virginia Commonwealth University, Richmond, VA, USA. 15. Department of Psychiatry, University of British Columbia, Vancouver, BC, Canada. 16. Department of Surgery (Neurosurgery), University of British Columbia, Vancouver, BC, Canada. 17. Department of Neurological Surgery, University of Louisville, Louisville, KY, USA. 18. Stanford Department of Neurosurgery, Stanford University School of Medicine, Stanford, CA, USA. 19. Department of Psychiatry, Stanford University School of Medicine, Stanford, CA, USA. 20. Department of Psychiatry, University of Massachusetts Medical School and UMass Memorial HealthCare, Worcester, MA, USA. 21. Department of Neuroscience and Experimental Therapeutics and the Department of Neurosurgery, Albany Medical College, Albany, NY, USA. 22. Department of Psychiatry and Biobehavioral Sciences, Geffen School of Medicine at UCLA, Los Angeles, CA, USA. 23. The Zucker Hillside Hospital, Northwell Health System, Glen Oaks, NY, USA; Hofstra Northwell School of Medicine, Hempstead, NY, USA. 24. Department of Neurosurgery, Center for Neuromodulation, NYU Langone Medical Center, New York, NY, USA. 25. Division of Neuroscience, School of Medicine, University of Dundee, Dundee, UK; Advanced Interventions Service, NHS Tayside, Ninewells Hospital and Medical School, Dundee, UK. 26. Clinical Studies Department, Abbott (previously St Jude Medical), Plano, TX, USA. 27. Department of Neurosurgery, Emory University School of Medicine, Atlanta, GA, USA. 28. Behavioural Neurobiology Laboratory, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health and Division of Neurosurgery, Toronto Western Hospital, Toronto, ON, Canada. 29. Department of Neurosurgery and Neuroscience, Toronto Western Hospital, Toronto, ON, Canada. 30. Department of Psychiatry and Department of Neurology, Emory University School of Medicine, Atlanta, GA, USA.
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. METHODS:Participants with treatment-resistant depression were implanted with a DBS system targeting bilateral subcallosal cingulate white matter and randomised to 6 months of active or sham DBS, followed by 6 months of open-label subcallosal cingulate DBS. Randomisation was computer generated with a block size of three at each site before the site started the study. The primary outcome was frequency of response (defined as a 40% or greater reduction in depression severity from baseline) averaged over months 4-6 of the double-blind phase. A futility analysis was performed when approximately half of the proposed sample received DBS implantation and completed the double-blind phase. At the conclusion of the 12-month study, a subset of patients were followed up for up to 24 months. The study is registered at ClinicalTrials.gov, number NCT00617162. FINDINGS: Before the futility analysis, 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. FUNDING: Abbott (previously St Jude Medical).
RCT Entities:
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. METHODS:Participants with treatment-resistant depression were implanted with a DBS system targeting bilateral subcallosal cingulate white matter and randomised to 6 months of active or sham DBS, followed by 6 months of open-label subcallosal cingulate DBS. Randomisation was computer generated with a block size of three at each site before the site started the study. The primary outcome was frequency of response (defined as a 40% or greater reduction in depression severity from baseline) averaged over months 4-6 of the double-blind phase. A futility analysis was performed when approximately half of the proposed sample received DBS implantation and completed the double-blind phase. At the conclusion of the 12-month study, a subset of patients were followed up for up to 24 months. The study is registered at ClinicalTrials.gov, number NCT00617162. FINDINGS: Before the futility analysis, 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. FUNDING: Abbott (previously St Jude Medical).
Authors: Ashan Veerakumar; Vineet Tiruvadi; Bryan Howell; Allison C Waters; Andrea L Crowell; Bradley Voytek; Patricio Riva-Posse; Lydia Denison; Justin K Rajendra; Johnathan A Edwards; Kelly R Bijanki; Ki Sueng Choi; Helen S Mayberg Journal: J Neurophysiol Date: 2019-07-17 Impact factor: 2.714
Authors: Ausaf A Bari; Charles B Mikell; Aviva Abosch; Sharona Ben-Haim; Robert J Buchanan; Allen W Burton; Stephen Carcieri; G Rees Cosgrove; Pierre-Francois D'Haese; Zafiris Jeffrey Daskalakis; Emad N Eskandar; Jason L Gerrard; Wayne K Goodman; Benjamin David Greenberg; Robert E Gross; Clement Hamani; Zelma H T Kiss; Peter Konrad; Brian H Kopell; Lothar Krinke; Jean-Philippe Langevin; Andres M Lozano; Donald Malone; Helen S Mayberg; Jonathan P Miller; Parag G Patil; DeLea Peichel; Erika A Petersen; Ali R Rezai; R Mark Richardson; Patricio Riva-Posse; Tejas Sankar; Jason M Schwalb; Helen Blair Simpson; Konstantin Slavin; Paul H Stypulkowski; Tor Tosteson; Peter Warnke; Jon T Willie; Kareem A Zaghloul; Joseph S Neimat; Nader Pouratian; Sameer A Sheth Journal: J Neurol Neurosurg Psychiatry Date: 2018-01-25 Impact factor: 10.154