Analgesic Efficacy of Multisite rTMS in Fibromyalgia Patients

The primary outcome measure will be the mean change from baseline over the course of 10 weeks (group x time interaction) in average pain intensity from the Brief Pain Inventory (scored on a 0-10 NRS with 0 = no pain and 10 = maximal pain intensity). Baseline average pain intensity will be assessed at inclusion, and just before the first rTMS session (Day 1) and will correspond to the average of these two values. Pain intensity will be further assessed immediately before each rTMS session at Days 2, 3, 4, 5 then at weeks 2, 3, 4, 6, 8, and finally 2 weeks after the last rTMS session at week 10.

Weekly average of daily patient-reported scores for pain intensity, fatigue, and sleep disturbance, recorded in a self-assessment diary completed throughout the study. Pain intensity and fatigue are each assessed on a numerical rating scale from 0 (no pain/no fatigue) to 10 (worst imaginable pain/worst imaginable fatigue), where higher scores indicate worse outcome. Sleep disturbance is assessed on a numerical rating scale from 0 (no interference) to 10 (completely disrupted sleep), where higher scores indicate worse outcome.

Pain intensity at the present moment assessed immediately after each rTMS session using a Numerical Rating Scale (NRS) ranging from 0 (no pain) to 10 (worst imaginable pain).

The time to onset of the therapeutic effect from the first stimulation, assessed by measuring 24-hour pain scores recorded in the patient's self-assessment diary.

The validated French version of the BPI (Cleeland and Ryan, 1994) will be used to assess maximum and minimum pain over the past 24 hours and at the present moment, as well as the impact of pain (general activity, mood, ability to walk, usual work, relationships with others, sleep, quality of life), on numerical scales from 0 to 10.

A validated self-report questionnaire specifically designed to assess the impact of fibromyalgia on quality of life. Scores range from 0 to 100, where higher scores indicate greater impact of fibromyalgia on functioning and worse outcome.

A self-report questionnaire assessing health-related quality of life across 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression), each rated on a 5-level scale from 1 (no problems) to 5 (extreme problems), where higher scores indicate worse outcome. A Visual Analogue Scale (EQ-VAS) ranging from 0 (worst imaginable health) to 100 (best imaginable health) is also included, where higher scores indicate better outcome.

A self-report questionnaire assessing the severity of anxiety and depressive symptoms over the past week. It consists of two 7-item subscales - one for anxiety (HADS-A) and one for depression (HADS-D) - each scored from 0 to 21, where higher scores indicate greater symptom severity.

A validated 9-item self-report questionnaire assessing the presence and severity of depressive symptoms over the past two weeks. Total scores range from 0 to 27, where higher scores indicate greater severity of depressive symptoms.

A 13-item self-report questionnaire assessing the tendency to magnify, ruminate, and feel helpless in response to pain. Each item is scored from 0 (not at all) to 4 (all the time), with a total score ranging from 0 to 52, where higher scores indicate greater catastrophizing.

A 12-item self-report questionnaire assessing the main dimensions of sleep quality, commonly used in chronic pain syndromes. Each item is rated on a 6-point categorical scale from 1 (all the time) to 6 (never). Scores are converted to a Sleep Problems Index ranging from 0 to 100, where higher scores indicate greater sleep disturbance.

A 15-item self-report questionnaire assessing the sensory and affective dimensions of pain. Eleven items evaluate the sensory dimension and 4 items evaluate the affective dimension, each rated on a scale from 0 (none) to 3 (severe). Total scores range from 0 to 45, where higher scores indicate greater pain intensity.

A validated questionnaire administered at the end of the study to assess the integrity of blinding. Participants are asked which treatment they believe they received (active, sham, or unsure) and the reasons for their belief (side effects, symptom relief, or other).

Single-item scales assessing the patient's and clinician's overall impression of change since the beginning of treatment, respectively. Both are rated on a 7-point scale ranging from 1 (very much improved) to 7 (very much worse), where higher scores indicate worse outcome.

A validated self-report questionnaire administered prior to treatment initiation to assess patients' beliefs about the credibility of the assigned treatment and their expectations regarding its therapeutic outcome. The first four items (Set 1), evaluating the cognitive dimensions of credibility and expectancy, will be used. Items are rated on a scale from 1 to 9, where higher scores indicate greater treatment credibility and expectancy.

The percentage of treatment responders (patients whose pain is reduced by at least 30% and 50%) at the end of treatment.

The safety and tolerability of the treatment, assessed by asking patients about any side effects experienced during the rTMS sessions.

Assess the correlation between baseline clinical variables - including pain characteristics, demographic factors, and psychosocial factors - and treatment response to active rTMS and sham stimulation.

Identify the correlation between motor cortical excitability and inhibition - assessed via motor evoked potentials (recorded from the first dorsal interosseous muscle of the hand) elicited by paired-pulse TMS - and treatment response to active rTMS and sham stimulation.

Identify the correlation between baseline cortical oscillatory patterns extracted from resting-state EEG recordings and treatment response to active rTMS and sham stimulation. EEG recordings will consist of a 5-minute eyes-open and a 5-minute eyes-closed session using a 32-channel cap.