Efficacy and Safety of Low-field Synchronized Transcranial Magnetic Stimulation (sTMS) for Treatment of Major Depression

Andrew F Leuchter; Ian A Cook; David Feifel; John W Goethe; Mustafa Husain; Linda L Carpenter; Michael E Thase; Andrew D Krystal; Noah S Philip; Mahendra T Bhati; William J Burke; Robert H Howland; Yvette I Sheline; Scott T Aaronson; Dan V Iosifescu; John P O'Reardon; William S Gilmer; Rakesh Jain; Karl S Burgoyne; Bill Phillips; Paul J Manberg; Joseph Massaro; Aimee M Hunter; Sarah H Lisanby; Mark S George

doi:10.1016/j.brs.2015.05.005

Efficacy and Safety of Low-field Synchronized Transcranial Magnetic Stimulation (sTMS) for Treatment of Major Depression

Brain Stimul. 2015 Jul-Aug;8(4):787-94. doi: 10.1016/j.brs.2015.05.005. Epub 2015 May 22.

Authors

Andrew F Leuchter¹, Ian A Cook², David Feifel³, John W Goethe⁴, Mustafa Husain⁵, Linda L Carpenter⁶, Michael E Thase⁷, Andrew D Krystal⁸, Noah S Philip⁶, Mahendra T Bhati⁷, William J Burke⁹, Robert H Howland¹⁰, Yvette I Sheline¹¹, Scott T Aaronson¹², Dan V Iosifescu¹³, John P O'Reardon¹⁴, William S Gilmer¹⁵, Rakesh Jain¹⁶, Karl S Burgoyne¹⁷, Bill Phillips¹⁸, Paul J Manberg¹⁸, Joseph Massaro¹⁹, Aimee M Hunter², Sarah H Lisanby⁸, Mark S George²⁰

Affiliations

¹ Department of Psychiatry and Biobehavioral Sciences and Neuromodulation Division, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA. Electronic address: afl@ucla.edu.
² Department of Psychiatry and Biobehavioral Sciences and Neuromodulation Division, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
³ Department of Psychiatry, UCSD School of Medicine, San Diego, CA, USA.
⁴ Institute of Living, Hartford Hospital, Hartford, CT, USA.
⁵ Department of Psychiatry, UT Southwestern Medical School, Dallas, TX, USA; Department of Psychiatry and Behavioral Sciences, Duke University School of Medicine, Durham, NC, USA.
⁶ Department of Psychiatry and Human Behavior, Butler Hospital, Alpert Medical School of Brown University, Providence, RI, USA.
⁷ Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
⁸ Department of Psychiatry and Behavioral Sciences, Duke University School of Medicine, Durham, NC, USA.
⁹ Department of Psychiatry, University of Nebraska School of Medicine, Omaha, NE, USA.
¹⁰ Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
¹¹ Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Department of Psychiatry, School of Medicine, Washington University, St. Louis, MO, USA.
¹² Sheppard Pratt Health System, Baltimore, MD, USA.
¹³ Department of Psychiatry, Icahn School of Medicine at Mt. Sinai, New York, NY, USA.
¹⁴ Department of Psychiatry, Rowan University School of Osteopathic Medicine, Stratford, NJ, USA.
¹⁵ Chicago TMS Specialists, Chicago, IL, USA.
¹⁶ RD Clinical Research, Lake Jackson, TX, USA.
¹⁷ Harbor-UCLA Medical Center, Torrance, CA, USA.
¹⁸ NeoSync, Inc., Waltham, MA, USA; NeoSync, Inc., Newport Beach, CA, USA.
¹⁹ Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA.
²⁰ Department of Psychiatry, Medical University of South Carolina, and the Ralph H. Johnson VA Medical Center, Charleston, SC, USA.

PMID: 26143022
DOI: 10.1016/j.brs.2015.05.005

Abstract

Background: Transcranial Magnetic Stimulation (TMS) customarily uses high-field electromagnets to achieve therapeutic efficacy in Major Depressive Disorder (MDD). Low-field magnetic stimulation also may be useful for treatment of MDD, with fewer treatment-emergent adverse events.

Objective/hypothesis: To examine efficacy, safety, and tolerability of low-field magnetic stimulation synchronized to an individual's alpha frequency (IAF) (synchronized TMS, or sTMS) for treatment of MDD.

Methods: Six-week double-blind sham-controlled treatment trial of a novel device that used three rotating neodymium magnets to deliver sTMS treatment. IAF was determined from a single-channel EEG prior to first treatment. Subjects had baseline 17-item Hamilton Depression Rating Scale (HamD17) ≥ 17.

Results: 202 subjects comprised the intent-to-treat (ITT) sample, and 120 subjects completed treatment per-protocol (PP). There was no difference in efficacy between active and sham in the ITT sample. Subjects in the PP sample (N = 59), however, had significantly greater mean decrease in HamD17 than sham (N = 60) (-9.00 vs. -6.56, P = 0.033). PP subjects with a history of poor response or intolerance to medication showed greater improvement with sTMS than did treatment-naïve subjects (-8.58 vs. -4.25, P = 0.017). Efficacy in the PP sample reflects exclusion of subjects who received fewer than 80% of scheduled treatments or were inadvertently treated at the incorrect IAF; these subgroups failed to separate from sham. There was no difference in adverse events between sTMS and sham, and no serious adverse events attributable to sTMS.

Conclusions: Results suggest that sTMS may be effective, safe, and well tolerated for treating MDD when administered as intended.

Keywords: Alpha oscillations; Clinical treatment trial; Electroencephalogram (EEG); Individual Alpha Frequency (IAF); Low-intensity magnetic field; Major Depressive Disorder; Neuromodulation; Oscillatory synchrony; Static magnet; Synchronized Transcranial Magnetic Stimulation (sTMS).

Publication types

Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

MeSH terms

Depressive Disorder, Major / therapy*
Double-Blind Method
Female
Humans
Male
Middle Aged
Psychiatric Status Rating Scales
Transcranial Magnetic Stimulation / adverse effects
Transcranial Magnetic Stimulation / methods*
Treatment Outcome