The Painfulness of Active, but not Sham, Transcranial Magnetic Stimulation Decreases Rapidly Over Time: Results From the Double-Blind Phase of the OPT-TMS Trial

• Type of Material: Article
• Authors: Jeffrey J Borckardt, Medical University of South Carolina; Ziad H. Nahas, Medical University of South Carolina; John Teal, Medical University of South Carolina; Sarah H. Lisanby, Duke University; William M. McDonald, Emory University; David Avery, University of Washington; Valerie Durkalski, Medical University of South Carolina; Martina Pavlicova, Columbia University; James Long, James Long Company; Harold A. Sackeim, Columbia University; Mark S. George, Medical University of South Carolina
• Language: English
• Date: 2013-11-01
• Publisher: Elsevier: 12 months
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2013 Elsevier Inc. All rights reserved. CC BY NC ND 4.0
• Final Published Version (URL): http://dx.doi.org/10.1016/j.brs.2013.04.009
• Title of Journal or Parent Work: Brain Stimulation
• ISSN: 1935-861X
• Volume: 6
• Issue: 6
• Start Page: 925
• End Page: 928
• Grant/Funding Information: Supported by the NIMH as the Optimization of TMS for Depression Trial, (OPT-TMS) involving grants 5R01MH069929 PI: AVERY, DAVID; 5R01MH069887 PI: GEORGE, MARK; 5R01MH069896 PI: GEORGE, MARK; 5R01MH069895 PI: LISANBY, SARAH; 5R01MH069886 PI: MCDONALD, WILLIAM.
• Keywords: Life Sciences & Biomedicine; Sham; DEPRESSION; TMS; Neurosciences; OPT-TMS; Clinical Neurology; Pain; PAIN; Neurosciences & Neurology; RTMS; Science & Technology; Transcranial magnetic stimulation; PREFRONTAL CORTEX; MOOD; Clinical trial; Depression; THERAPY
• Research Categories: Biology, Neuroscience; Health Sciences, Radiology

Abstract

Background: Daily left prefrontal repetitive transcranial magnetic stimulation (rTMS) over several weeks is an FDA approved treatment for major depression. Although rTMS is generally safe when administered using the FDA guidelines, there are a number of side effects that can make it difficult for patients to complete a course of rTMS. Many patients report that rTMS is painful, although patients appear to accommodate to the initial painfulness. The reduction in pain is hypothesized to be due to prefrontal stimulation and is not solely explained by accommodation to the stimulation. Methods: In a recent 4 site randomized controlled trial (using an active electrical sham stimulation system) investigating the antidepressant effects of daily left dorsolateral prefrontal rTMS (Optimization of TMS, or OPT-TMS), the procedural painfulness of TMS was assessed before and after each treatment session. Computerized visual analog scale ratings were gathered before and after each TMS session in the OPT-TMS trial. Stimulation was delivered with an iron core figure-8 coil (Neuronetics) with the following parameters: 10 Hz, 120% MT (EMG-defined), 4 s pulse train, 26 s inter-train interval, 3000 pulses per session, one 37.5 min session per day. After each session, procedural pain (pain at the beginning of the TMS session, pain toward the middle, and pain toward then end of the session) ratings were collected at all 4 sites. From the 199 patients randomized, we had usable data from 142 subjects for the initial 15 TMS sessions (double-blind phase) delivered over 3 weeks (142 × 2 × 15 = 4260 rating sessions). Results: The painfulness of real TMS was initially higher than that of the active sham condition. Over the 15 treatment sessions, subjective reports of the painfulness of rTMS (during the beginning, middle and end of the session) decreased significantly 37% from baseline in those receiving active TMS, with no change in painfulness in those receiving sham. This reduction, although greatest in the first few days, continued steadily over the 3 weeks. Overall, there was a decay rate of 1.56 VAS points per session in subjective painfulness of the procedure in those receiving active TMS. Discussion: The procedural pain of left, prefrontal rTMS decreases over time, independently of other emotional changes, and only in those receiving active TMS. These data suggest that actual TMS stimulation of prefrontal cortex maybe related to the reduction in pain, and that it is not a non-specific accommodation to pain. This painfulness reduction softly corresponds with later clinical outcome. Further work is needed to better understand this phenomenon and whether acute within-session or over time painfulness changes might be used as short-term biomarkers of antidepressant response.