Meta-Analysis Provides Continued Support for Efficacy of Neuromodulation for Migraine Treatment
A new random-effects meta-analysis of neuromodulation devices for migraine treatment has been published in The Journal of Headache and Pain. A systematic literature search identified 7 randomized controlled clinical trials of neuromodulation for acute migraine treatment that used outcome measures of pain freedom or pain relief at 2 hours. Using 6 of the studies, pooled quantitative data analysis was conducted for each neuromodulation modality; comparisons among modalities could not be made because of differences in trial design, mechanisms of action, and doses. Because blinding can be difficult or even impossible for several neurostimulation techniques, such a design was not required.
Subgroup analysis was possible only for remote electrical neuromodulation (REN), for which there were 2 available studies. Pooled data analysis suggested efficacy of REN for acute migraine treatment, with an effect size of 2.14 (1.34-3.40) for treatment compared to sham stimulation. Authors of the analysis note that both studies were done by the same research team and recommend independent verification of these results to confirm efficacy. Data for 4 other neuromodulation modalities could not be evaluated for efficacy in this meta-analysis because only 1 study was available for each. These modalities included supraorbital and occipital transcutaneous electrical nerve stimulation (TENS), noninvasive vagal nerve stimulation (VNS), and kinetic oscillation stimulation. In these individual studies, there were positive effects for the other modalities.
"As noninvasive neuromodulation is an emerging field in the treatment of migraine, an unbiased systemic review was important to understand what may really be benefitting patients," said professor Stephen Silberstein, MD, director of the Headache Center at the Jefferson University Hospital in Philadelphia. "While the industry should conduct more studies to understand the potential of neuromodulation for migraine treatment, this study certainly helps comparing between the different emerging techniques. REN, based on triggering conditioned pain modulation, stands out with very promising results for acute migraine treatment."
The literature search also identified 31 randomized controlled clinical trials with treatment lasting at least 4 weeks for preventive treatment of migraine. In these studies, outcomes included reduction in monthly headache days. Using 27 of these studies, efficacy was evaluated with pooled data analysis for each treatment modality.
Supraorbital and percutaneous TENS and high-frequency repetitive transcranial magnetic stimulation (rTMS) over the primary motor cortex (M1) were found effective for preventive migraine treatment. Invasive occiptal nerve stimulation was effective, but with heterogeneity of effect size. VNS, left prefrontal cortex rTMS, and cathodal transcranial direct current stimulation (tDCS) over the M1 had no significant effects and heterogeneity was high. In a single study, percutaneous mastoid electrical stimulation for prevention of episodic migraine had a large effect size (absolute difference of 2.87 days/month reduction). Peripheral pulsed electromagnetic fields applied to the wrist was not effective.
The device is a therapeutic wearable with a prescription that implements REN to treat the pain, aura, and symptoms caused by migraine. The device is worn on the upper arm, controlled through an application on a smartphone, also serving as a migraine diary.
A prospective single arm open-label multicenter trial to evaluate the efficacy and safety of the REN device in individuals with chronic migraine. Eligible participants were trained to use a smartphone migraine diary application. During the 4 weeks of phase 2, participants will be instructed to report all their migraines and headaches at onset, 2 hours and 24 hours post report.
A 4-week treatment phase in which participants will be asked to treat their migraine headaches with the REN device and report it using the smartphone application at baseline, 2 hours and 24 hours post-treatment. An 8-week follow-up phase in which participants will incorporate the device into their usual care according to their preference. Participants will report all their migraines or headaches at onset, 2 hours post report and 24 hours post report.