title: Clinically Effective Treatment of Fibromyalgia Pain With High-Definition Transcranial Direct Current Stimulation: Phase II Open-Label Dose Optimization.
abstract: Despite promising preliminary results in treating fibromyalgia (FM) pain, no neuromodulation technique has been adopted in clinical practice because of limited efficacy, low response rate, or poor tolerability. This phase II open-label trial aims to define a methodology for a clinically effective treatment of pain in FM by establishing treatment protocols and screening procedures to maximize efficacy and response rate. High-definition transcranial direct current stimulation (HD-tDCS) provides targeted subthreshold brain stimulation, combining tolerability with specificity. We aimed to establish the number of HD-tDCS sessions required to achieve a 50% FM pain reduction, and to characterize the biometrics of the response, including brain network activation pain scores of contact heat-evoked potentials. We report a clinically significant benefit of a 50% pain reduction in half (n = 7) of the patients (N = 14), with responders and nonresponders alike benefiting from a cumulative effect of treatment, reflected in significant pain reduction (P = .035) as well as improved quality of life (P = .001) over time. We also report an aggregate 6-week response rate of 50% of patients and estimate 15 as the median number of HD-tDCS sessions to reach clinically meaningful outcomes. The methodology for a pivotal FM neuromodulation clinical trial with individualized treatment is thus supported.
  Registered in Clinicaltrials.gov under registry number NCT01842009.
  
  
  CONCLUSIONS
  In this article, an optimized protocol for the treatment of fibromyalgia pain with targeted subthreshold brain stimulation using high-definition transcranial direct current stimulation is outlined.
authors.affiliation: Laboratory of Neuromodulation, Department of Physical Medicine and Rehabilitation, Spaulding Rehabilitation Hospital and Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Laura
authors.initials: L
authors.lastname: Castillo-Saavedra
authors.affiliation: Laboratory of Neuromodulation, Department of Physical Medicine and Rehabilitation, Spaulding Rehabilitation Hospital and Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts; Department of Biomedical Engineering, The City College of the City University of New York, New York, New York.
authors.forename: Nigel
authors.initials: N
authors.lastname: Gebodh
authors.affiliation: Department of Biomedical Engineering, The City College of the City University of New York, New York, New York.
authors.forename: Marom
authors.initials: M
authors.lastname: Bikson
authors.affiliation: Laboratory of Neuromodulation, Department of Physical Medicine and Rehabilitation, Spaulding Rehabilitation Hospital and Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Camilo
authors.initials: C
authors.lastname: Diaz-Cruz
authors.affiliation: Laboratory of Neuromodulation, Department of Physical Medicine and Rehabilitation, Spaulding Rehabilitation Hospital and Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts; Postgraduate Program in Interactive Processes of Organs and Systems, Federal University of Bahia, Salvador, Bahia, Brazil.
authors.forename: Rivail
authors.initials: R
authors.lastname: Brandao
authors.affiliation: Laboratory of Neuromodulation, Department of Physical Medicine and Rehabilitation, Spaulding Rehabilitation Hospital and Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Livia
authors.initials: L
authors.lastname: Coutinho
authors.affiliation: Department of Biomedical Engineering, The City College of the City University of New York, New York, New York.
authors.forename: Dennis
authors.initials: D
authors.lastname: Truong
authors.affiliation: Department of Biomedical Engineering, The City College of the City University of New York, New York, New York; Soterix Medical, Inc, New York, New York.
authors.forename: Abhishek
authors.initials: A
authors.lastname: Datta
authors.affiliation: ElMindA Ltd, Herzliya, Israel.
authors.forename: Revital
authors.initials: R
authors.lastname: Shani-Hershkovich
authors.affiliation: ElMindA Ltd, Herzliya, Israel.
authors.forename: Michal
authors.initials: M
authors.lastname: Weiss
authors.affiliation: ElMindA Ltd, Herzliya, Israel.
authors.forename: Ilan
authors.initials: I
authors.lastname: Laufer
authors.affiliation: ElMindA Ltd, Herzliya, Israel.
authors.forename: Amit
authors.initials: A
authors.lastname: Reches
authors.affiliation: ElMindA Ltd, Herzliya, Israel; Tel Aviv University, Tel Aviv, Israel.
authors.forename: Ziv
authors.initials: Z
authors.lastname: Peremen
authors.affiliation: ElMindA Ltd, Herzliya, Israel; Ben Gurion University, Beersheba, Israel.
authors.forename: Amir
authors.initials: A
authors.lastname: Geva
authors.affiliation: Department of Biomedical Engineering, The City College of the City University of New York, New York, New York.
authors.forename: Lucas C
authors.initials: LC
authors.lastname: Parra
authors.affiliation: Laboratory of Neuromodulation, Department of Physical Medicine and Rehabilitation, Spaulding Rehabilitation Hospital and Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts. Electronic address: ffregni@mgh.harvard.edu.
authors.forename: Felipe
authors.initials: F
authors.lastname: Fregni
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D005356:Fibromyalgia / Q000503:physiopathology / Q000628:therapy*; D006358:Hot Temperature; D006801:Humans; D008297:Male; D008875:Middle Aged; D059408:Pain Management / Q000379:methods; D010147:Pain Measurement; D017288:Pain Threshold / Q000502:physiology; D011788:Quality of Life; D065908:Transcranial Direct Current Stimulation / Q000379:methods*; D016896:Treatment Outcome
keywords: Fibromyalgia; high-definition transcranial direct current stimulation; motor cortex; noninvasive brain stimulation; pain