Dolors Puigdemont1, Maria Portella1, Rosario Pérez-Egea2, Joan Molet3, Alexandre Gironell4, Javier de Diego-Adeliño1, Anna Martín1, Rodrigo Rodríguez3, Enric Àlvarez1, Francesc Artigas5, Víctor Pérez1. 1. Department of Psychiatry, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Centro de Investigación Biomédica en Red de Salud Mental, Institut d'Investigació Biomèdica Sant Pau, Barcelona, Spain. 2. From the Department of Psychiatry, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Centro de Investigación Biomédica en Red de Salud Mental, Institut d'Investigació Biomèdica Sant Pau, Barcelona, Spain. 3. Department of Neurosurgery, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Institut d'Investigació Biomèdica Sant Pau, Barcelona, Spain. 4. Department of Neurology, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona (UAB), Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas, Institut d'Investigació Biomèdica Sant Pau, Barcelona, Spain. 5. Department of Neurochemistry and Neuropharmacology, Institut d'Investigacions Biomèdiques de Barcelona, IDIBAPS, Consejo Superior de Investigaciones Cientificas, IDIBAPS, Centro de Investigación Biomédica en Red de Salud Mental, Barcelona, Spain.
Abstract
BACKGROUND: To date, antidepressant drugs show limited efficacy, leaving a large number of patients experiencing severe and persistent symptoms of major depression. Previous open-label clinical trials have reported significant sustained improvements with deep brain stimulation (DBS) of the subcallosal cingulate gyrus (SCG) in patients with severe, chronic treatment-resistant depression (TRD). This study aimed to confirm the efficacy and measure the impact of discontinuation of the electrical stimulation. METHODS: We conducted a 6-month double-blind, randomized, sham-controlled crossover study in implanted patients with previous severe TRD who experienced full remission after chronic stimulation. After more than 3 months of stable remission, patients were randomly assigned to 2 treatment arms: the ON-OFF arm, which involved active electrode stimulation for 3 months followed by sham stimulation for 3 months, and the OFF-ON arm, which involved sham stimulation for 3 months followed by active stimulation for 3 months. The primary outcome measure was the difference in the 17-item Hamilton Rating Scale for Depression (HAMD-17) total score between sham and active stimulation. RESULTS: We enrolled 5 patients in our trial. A Friedman repeated-measures analysis of variance revealed a significant effect of treatment (χ(2)1 = 5.0, p = 0.025) in patients with higher depression scores during sham stimulation. At the end of active stimulation, depression was remitted in 4 of 5 patients and none of them had experienced a relapse, whereas at the end of sham stimulation, 2 patients remained in remission, 2 relapsed and 1 showed a progressive worsening without reaching relapse criteria. LIMITATIONS: The small sample size limited the statistical power and external validity. CONCLUSION: These preliminary findings indicate that DBS of the SCG is an effective and safe treatment for severe forms of TRD and that continuous electrical stimulation is required to maintain therapeutic effects. TRIAL REGISTRATION: NCT01268137 (ClinicalTrials.gov).
RCT Entities:
BACKGROUND: To date, antidepressant drugs show limited efficacy, leaving a large number of patients experiencing severe and persistent symptoms of major depression. Previous open-label clinical trials have reported significant sustained improvements with deep brain stimulation (DBS) of the subcallosal cingulate gyrus (SCG) in patients with severe, chronic treatment-resistant depression (TRD). This study aimed to confirm the efficacy and measure the impact of discontinuation of the electrical stimulation. METHODS: We conducted a 6-month double-blind, randomized, sham-controlled crossover study in implanted patients with previous severe TRD who experienced full remission after chronic stimulation. After more than 3 months of stable remission, patients were randomly assigned to 2 treatment arms: the ON-OFF arm, which involved active electrode stimulation for 3 months followed by sham stimulation for 3 months, and the OFF-ON arm, which involved sham stimulation for 3 months followed by active stimulation for 3 months. The primary outcome measure was the difference in the 17-item Hamilton Rating Scale for Depression (HAMD-17) total score between sham and active stimulation. RESULTS: We enrolled 5 patients in our trial. A Friedman repeated-measures analysis of variance revealed a significant effect of treatment (χ(2)1 = 5.0, p = 0.025) in patients with higher depression scores during sham stimulation. At the end of active stimulation, depression was remitted in 4 of 5 patients and none of them had experienced a relapse, whereas at the end of sham stimulation, 2 patients remained in remission, 2 relapsed and 1 showed a progressive worsening without reaching relapse criteria. LIMITATIONS: The small sample size limited the statistical power and external validity. CONCLUSION: These preliminary findings indicate that DBS of the SCG is an effective and safe treatment for severe forms of TRD and that continuous electrical stimulation is required to maintain therapeutic effects. TRIAL REGISTRATION: NCT01268137 (ClinicalTrials.gov).
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