A research team from France and Brazil conducted the first long-term trial of repetitive transcranial magnetic stimulation (rTMS) for pain relief in patients with chronic widespread pain due to fibromyalgia. There were favorable outcomes on pain and quality of life indicators but there also were limitations of this study that must be considered.
In this trial reported in the June edition of the journal PAIN, 40 adult female patients with fibromyalgia were randomly assigned in double-blind fashion to 2 groups: one receiving active rTMS (n = 20) and the other receiving sham stimulation (n = 20), applied to the left primary motor cortex [Mhalla et al. 2011]. Subjects were all right-handed, mean age 50 years, and had experienced pain for 13.5 years on average.
The stimulation protocol consisted of 14 sessions: an “induction phase” of 5 daily sessions followed by a 9-session “maintenance phase” consisting of 3 sessions one week apart, then 3 sessions two-weeks apart, and finally 3 sessions one month apart. The primary outcome was average pain intensity during the last 24 hours, measured before each rTMS stimulation from day 1 to week 21 and at week 25 (1 month after the last stimulation). Other outcomes measured included quality of life, mood and anxiety, and several parameters of motor cortex excitability.
Thirty patients completed the study (16 in the active rTMS group and 14 in the sham group). Active rTMS significantly reduced pain intensity from day 5 to week 25 at the conclusion of the trial. These analgesic effects also were associated with long-term improvement in factors related to quality of life — including fatigue, morning tiredness, general activity, walking, and sleep — and were directly correlated with an inhibition of cortical excitation in the brain.
Side effects were minimal, 2 subjects experienced headache (1 each in the active and sham therapy groups) and 1 patient in the active stimulation group reported transient nausea. Therefore, the researchers conclude that rTMS may be a relatively safe and worthwhile new therapeutic option in patients with fibromyalgia.
COMMENTARY: Transcranial magnetic stimulation (TMS) is noninvasive and uses either single or repetitive applications of low frequency magnetic pulses to the brain. Two decades of clinical experience with TMS have demonstrated it to be relatively safe and promising in the diagnosis, monitoring, and treatment of neurological and psychiatric disease (eg, depression). A previous Pain-Topics UPDATE [here] discussed magnetic therapies for pain, including single pulse transcranial magnetic stimulation (sTMS), which was found to help relieve pain in persons suffering migraine with aura.
The present study by Mhalla et al. used repetitive pulse TMS, which is currently approved for treating depression but not pain, as yet, in the United States. It is always disappointing when researchers conduct important investigations such as this and achieve noteworthy outcomes, but enroll too few patients to confirm external validity for everyday pain practice. Furthermore, while effect sizes for pain reduction on a 10 point VAS (visual analog scale) were moderate to large for rTMS compared with placebo/sham, ranging from 0.66 to 1.19, there was a decline of active treatment effectiveness during the final, once-monthly maintenance phase.
During the peak effect at week 9, the absolute improvement in VAS score from baseline in the active rTMS group was only 1.7 points, or a 27% pain reduction from baseline, which is quite modest. However, improvements in the other outcome measures suggest that rTMS effects go beyond the sensory component of pain in fibromyalgia and may influence more global improvements in the chronic pain state of the patients.
Therefore, while this outpatient therapy may be promising the research seems incomplete. For one thing, the frequency of rTMS sessions needs better definition, and one-month intervals seem insufficient for long-term maintenance. However, the authors concede that more frequent weekly or biweekly sessions may not be realistic in clinical practice. There also is the possibility that rTMS might offer greatest benefits as an add-on component to a multimodal approach to fibromyalgia but this has not been explored.
REFERENCE: Mhalla A, Baudic S, Ciampi d Andrade D, et al. Long-term maintenance of the analgesic effects of transcranial magnetic stimulation in fibromyalgia. PAIN. 2011;152:1478–1485 [abstract here].