PMID- 38123726 OWN - NLM STAT- Publisher LR - 20231220 IS - 1476-5578 (Electronic) IS - 1359-4184 (Linking) DP - 2023 Dec 20 TI - Effect of non-invasive spinal cord stimulation in unmedicated adults with major depressive disorder: a pilot randomized controlled trial and induced current flow pattern. LID - 10.1038/s41380-023-02349-9 [doi] AB - Converging theoretical frameworks suggest a role and a therapeutic potential for spinal interoceptive pathways in major depressive disorder (MDD). Here, we aimed to evaluate the antidepressant effects and tolerability of transcutaneous spinal direct current stimulation (tsDCS) in MDD. This was a double-blind, randomized, sham-controlled, parallel group, pilot clinical trial in unmedicated adults with moderate MDD. Twenty participants were randomly allocated (1:1 ratio) to receive "active" 2.5 mA or "sham" anodal tsDCS sessions with a thoracic (anode; T10)/right shoulder (cathode) electrode montage 3 times/week for 8 weeks. Change in depression severity (MADRS) scores (prespecified primary outcome) and secondary clinical outcomes were analyzed with ANOVA models. An E-Field model was generated using the active tsDCS parameters. Compared to sham (n = 9), the active tsDCS group (n = 10) showed a greater baseline to endpoint decrease in MADRS score with a large effect size (-14.6 +/- 2.5 vs. -21.7 +/- 2.3, p = 0.040, d = 0.86). Additionally, compared to sham, active tsDCS induced a greater decrease in MADRS "reported sadness" item (-1.8 +/- 0.4 vs. -3.2 +/- 0.4, p = 0.012), and a greater cumulative decrease in pre/post tsDCS session diastolic blood pressure change from baseline to endpoint (group difference: 7.9 +/- 3.7 mmHg, p = 0.039). Statistical trends in the same direction were observed for MADRS "pessimistic thoughts" item and week-8 CGI-I scores. No group differences were observed in adverse events (AEs) and no serious AEs occurred. The current flow simulation showed electric field at strength within the neuromodulation range (max. ~0.45 V/m) reaching the thoracic spinal gray matter. The results from this pilot study suggest that tsDCS is feasible, well-tolerated, and shows therapeutic potential in MDD. This work also provides the initial framework for the cautious exploration of non-invasive spinal cord neuromodulation in the context of mental health research and therapeutics. The underlying mechanisms warrant further investigation. Clinicaltrials.gov registration: NCT03433339 URL: https://clinicaltrials.gov/ct2/show/NCT03433339 . CI - (c) 2023. The Author(s). FAU - Romo-Nava, Francisco AU - Romo-Nava F AUID- ORCID: 0000-0002-5894-3701 AD - Lindner Center of HOPE, Mason, OH, USA. romofo@ucmail.uc.edu. AD - Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, Cincinnati, OH, USA. romofo@ucmail.uc.edu. FAU - Awosika, Oluwole O AU - Awosika OO AD - Department of Neurology and Rehabilitation Medicine, University of Cincinnati College of Medicine, Cincinnati, OH, USA. FAU - Basu, Ishita AU - Basu I AD - Department of Neurosurgery, University of Cincinnati College of Medicine, Cincinnati, OH, USA. FAU - Blom, Thomas J AU - Blom TJ AD - Lindner Center of HOPE, Mason, OH, USA. AD - Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, Cincinnati, OH, USA. FAU - Welge, Jeffrey AU - Welge J AD - Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, Cincinnati, OH, USA. AD - Department of Environmental and Public Health Sciences, University of Cincinnati College of Medicine, Cincinnati, OH, USA. FAU - Datta, Abhishek AU - Datta A AD - Research and Development, Soterix Medical, Inc, New York, NY, USA. FAU - Guillen, Alexander AU - Guillen A AD - Research and Development, Soterix Medical, Inc, New York, NY, USA. FAU - Guerdjikova, Anna I AU - Guerdjikova AI AD - Lindner Center of HOPE, Mason, OH, USA. AD - Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, Cincinnati, OH, USA. FAU - Fleck, David E AU - Fleck DE AD - Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, Cincinnati, OH, USA. FAU - Georgiev, Georgi AU - Georgiev G AD - Lindner Center of HOPE, Mason, OH, USA. FAU - Mori, Nicole AU - Mori N AD - Lindner Center of HOPE, Mason, OH, USA. AD - Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, Cincinnati, OH, USA. FAU - Patino, Luis R AU - Patino LR AD - Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, Cincinnati, OH, USA. FAU - DelBello, Melissa P AU - DelBello MP AD - Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, Cincinnati, OH, USA. FAU - McNamara, Robert K AU - McNamara RK AD - Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, Cincinnati, OH, USA. FAU - Buijs, Ruud M AU - Buijs RM AUID- ORCID: 0000-0003-3894-4632 AD - Departamento de Fisiologia Celular y Biologia, Instituto de Investigaciones Biomedicas, Universidad Nacional Autonoma de Mexico, Mexico City, Mexico. FAU - Frye, Mark A AU - Frye MA AUID- ORCID: 0000-0001-6997-4215 AD - Department of Psychiatry and Psychology, Mayo Clinic, Rochester, MN, USA. FAU - McElroy, Susan L AU - McElroy SL AD - Lindner Center of HOPE, Mason, OH, USA. AD - Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, Cincinnati, OH, USA. LA - eng SI - ClinicalTrials.gov/NCT03433339 GR - 26649/Brain and Behavior Research Foundation (Brain & Behavior Research Foundation)/ GR - K23MH120503/U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH)/ PT - Journal Article DEP - 20231220 PL - England TA - Mol Psychiatry JT - Molecular psychiatry JID - 9607835 SB - IM EDAT- 2023/12/21 00:41 MHDA- 2023/12/21 00:41 CRDT- 2023/12/20 23:39 PHST- 2023/05/30 00:00 [received] PHST- 2023/11/27 00:00 [accepted] PHST- 2023/11/20 00:00 [revised] PHST- 2023/12/21 00:41 [medline] PHST- 2023/12/21 00:41 [pubmed] PHST- 2023/12/20 23:39 [entrez] AID - 10.1038/s41380-023-02349-9 [pii] AID - 10.1038/s41380-023-02349-9 [doi] PST - aheadofprint SO - Mol Psychiatry. 2023 Dec 20. doi: 10.1038/s41380-023-02349-9.