rTMS in fibromyalgia
A randomized trial evaluating QoL and its brain metabolic substrate
Abstract
Objective:
This double-blind, randomized, placebo-controlled study investigated the impact of repetitive transcranial magnetic stimulation (rTMS) on quality of life (QoL) of patients with fibromyalgia, and its possible brain metabolic substrate.
Methods:
Thirty-eight patients were randomly assigned to receive high-frequency rTMS (n = 19) or sham stimulation (n = 19), applied to left primary motor cortex in 14 sessions over 10 weeks. Primary clinical outcomes were QoL changes at the end of week 11, measured using the Fibromyalgia Impact Questionnaire (FIQ). Secondary clinical outcomes were mental and physical QoL component measured using the 36-Item Short Form Health Survey (SF-36), but also pain, mood, and anxiety. Resting-state [18F]-fluorodeoxyglucose-PET metabolism was assessed at baseline, week 2, and week 11. Whole-brain voxel-based analysis was performed to study between-group metabolic changes over time.
Results:
At week 11, patients of the active rTMS group had greater QoL improvement in the FIQ (p = 0.032) and in the mental component of the SF-36 (p = 0.019) than the sham stimulation group. No significant impact was found for other clinical outcomes. Compared with the sham stimulation group, patients of the active rTMS group presented an increase in right medial temporal metabolism between baseline and week 11 (p < 0.001), which was correlated with FIQ and mental component SF-36 concomitant changes (r = −0.38, p = 0.043; r = 0.51, p = 0.009, respectively). QoL improvement involved mainly affective, emotional, and social dimensions.
Conclusion:
Our study shows that rTMS improves QoL of patients with fibromyalgia. This improvement is associated with a concomitant increase in right limbic metabolism, arguing for a neural substrate to the impact of rTMS on emotional dimensions involved in QoL.
Classification of evidence:
This study provides Class II evidence that rTMS compared with sham rTMS improves QoL in patients with fibromyalgia.
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Information & Authors
Information
Published In
Neurology®
Volume 82 • Number 14 • April 8, 2014
Pages: 1231-1238
Copyright
© 2014 American Academy of Neurology.
Publication History
Received: March 1, 2013
Accepted: January 6, 2014
Published online: March 26, 2014
Published in print: April 8, 2014
Authors
Author Contributions
L.B.: drafting/revising the manuscript for content, including medical writing for content, analysis or interpretation of data, statistical analysis. A. Dousset: drafting/revising the manuscript for content, including medical writing for content, analysis or interpretation of data. P.R.: study concept or design, analysis or interpretation of data, acquisition of data, study supervision or coordination, obtaining funding. N.D.: study concept or design, acquisition of data. S.C.: study concept or design, acquisition of data, obtaining funding. V.P.: analysis or interpretation of data. S.K.: drafting/revising the manuscript for content, including medical writing for content, analysis or interpretation of data. O.M.: study concept or design, obtaining funding. A. Donnet: drafting/revising the manuscript for content, including medical writing for content, analysis or interpretation of data, study supervision or coordination. E.G.: drafting/revising the manuscript for content, including medical writing for content, study concept or design, analysis or interpretation of data, acquisition of data, statistical analysis, study supervision or coordination, obtaining funding.
Disclosure
The authors report no disclosures relevant to the manuscript. Go to Neurology.org for full disclosures.
Study Funding
Supported by Inserm (Centre d’Investigation Clinique, CIC, Hôpital de la Conception, Marseille) and AP-HM (AORC 2008/01). International Standard Randomized Controlled Trial Number: NCT00697398.
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The Boyer et al. paper [1] diverges, without disclosure, from the registered protocol for this trial. Throughout the paper, the authors stated that quality of life (QOL) was the a priori established primary outcome measure and outlined a case for that decision. This appears as a departure from the www.clinicaltrials.gov register record (NCT00697398) that identifies analgesic efficiency as primary outcome and QOL as secondary outcome. Were the original hypotheses about pain and QOL retained, necessary corrections for multiple testing would likely obviate the significant findings presented in the paper.
The effect on QOL was small and imprecise; not reflected in concomitant change on a different QOL scale or in improvement across any outcomes that might underpin such improvement in QOL. The improvement observed at 11 weeks was not apparent after the initial 2 weeks of intensive stimulation. It is possible that the improvement in QOL was not related to the rTMS treatment. A substantially more conservative interpretation is warranted for a possibly negative trial of rTMS for fibromyalgia.
1.Boyer L, Dousset A, Roussel P, et al. rTMS in fibromyalgia A randomized trial evaluating QoL and its brain metabolic substrate. Neurology 2014; 82: 1231-1238.
For disclosures, please contact the editorial office at [email protected].
We thank Parkitny et al. for their comments. The Fibromyalgia Impact Questionnaire (FIQ) was the primary criterion for our evaluation [1] since it is the most common instrument used in clinical studies to monitor response to treatment over time, specifically in patients with fibromyalgia (FM). [2,3] Above all, FIQ is the most responsive measure to perceived clinical improvement and has been recommended as a primary endpoint in FM clinical trials [3].
FIQ evaluates the impact of chronic pain disease on daily life with a multidimensional approach including functioning, symptoms, and pain, anxiety, and depression. [4] The pain evaluation at this step encompassed both pain and its functional consequences. Secondary outcomes were mono-dimensional evaluations of quality of life (QoL), pain, anxiety and depression using generic scales, nonspecific of FM.
The issues raised by Parkitny et al. were included in the limitations section of the Discussion. Based on our neuroimaging findings, we also proposed changes for future rTMS protocols.We also mentioned that the trial was negative on pain (and also in anxiety and depression), but positive on QoL using multidimensional and mono-dimensional approaches. Randomized controlled trial (RCT) is the gold standard for clinical research, representing the best way to determine efficacy and effectiveness of therapeutic strategies for intervention and prevention programs.
We hope our results, despite limitations, will contribute to the development of more effective therapies.
1. Boyer L, Dousset A, Roussel P, et al. rTMS in fibromyalgia A randomized trial evaluating QoL and its brain metabolic substrate. Neurology 2014;82:1231-1238.
2. Bennett R. The Fibromyalgia Impact Questionnaire (FIQ): a review of its development, current version, operating characteristics and uses. Clin Exp Rheumatol 2005;23:S154-162.
3. Dunkl PR, Taylor AG, McConnell GG, Alfano AP, Conaway MR. Responsiveness of fibromyalgia clinical trial outcome measures. J Rheumatol2000; 27: 2683-2691.
4. Williams DA, Arnold LM. Measures of fibromyalgia: Fibromyalgia Impact Questionnaire (FIQ), Brief Pain Inventory (BPI), Multidimensional Fatigue Inventory (MFI-20), Medical Outcomes Study (MOS) Sleep Scale, and Multiple Ability Self-Report Questionnaire (MASQ). Arthritis Care Res (Hoboken) 2011;63:S86-97.
For disclsoures, please contact the editorial office at [email protected].