Daniel M. Keller, PhD
September 18, 2017
External trigeminal nerve stimulation (eTNS) can be an effective treatment for acute migraine even when applied well into an attack, a new study suggests.
Researchers presented the results here of a trial involving patients with migraine with or without aura with pain present at least 3 hours before treatment.
"The results of this multicenter, double-blind, randomized, sham-controlled trial demonstrate that eTNS is an effective and well-tolerated treatment for the acute treatment of migraine, offering a nonpharmacologic option for patients who may not be able to tolerate abortive medications," Denise Chou, MD, Columbia University, New York City, told delegates here at the 18th Congress of the International Headache Society (IHC) 2017.
She described the need for nonpharmacologic migraine therapies in light of the "many contraindications and moderate to severe side effects," of the drugs used as acute treatments. In addition, there are risks with these treatments, including headache chronification and medication overuse headache.
Supraorbital eTNS devices are already approved for the prevention of episodic migraine, and open-label safety and efficacy data showed their benefit for the acute treatment of migraine.
The aim of the current randomized, sham-controlled trial was to assess the efficacy and safety of eTNS in the acute treatment of migraine. The eTNS device delivered rectangular biphasic pulses of 16 mA (uptitrated over 14 minutes) at 100 Hz and 250 μs for 1 hour. The targets were the supratrochlearis and supraorbitalis nerves.
A sham stimulus of 1 Hz/250 μs with a maximum current of 5 mA for 1 hour provided a feeling of a paresthesia. Study patients were randomly assigned 1:1 to a single treatment with active or sham stimulation.
Participants were 18 to 65 years (mean age, about 40 years), were male or female, had a history or episodic or chronic migraine with or without aura, and were experiencing a migraine attack for at least 3 hours with stable pain intensity for at least 1 hour. They could not have taken an acute migraine medication within the past 3 hours.
The primary endpoint of the trial was the mean change in pain score at 1 hour compared with baseline. Secondary endpoints included change in pain scores at 2 hours and 24 hours from baseline and the proportion of patients who did not use pain medications at these time points.
In this analysis, Dr Chou reported on 57 patients who were evaluable for these endpoints.
At 1 hour, the active stimulus group reported a 65% decrease in pain on a visual analogue scale (VAS) compared with baseline. The sham control group reported a 32% decrease (P < .001). More patients in the active stimulus group were pain-free at all time points.
Table. Proportion of Patients Pain-Free at 1, 2, and 24 Hours
|Time Point||Stimulus (%)||Sham Control (%)||P Value|
Similarly, more patients in the active treatment group (63%) had at least 50% pain relief at 1 hour vs sham controls (31%; P = .0017). There was no significant difference between the groups in the use of rescue medication within 24 hours.
No serious adverse effects occurred, and only 1 patient reported a minor adverse effect of self-limited nausea. Any patient who experienced discomfort during the stimulation could stabilize it for the duration of the treatment at that intensity by pushing a button on the device.
Dr Chou said the 1-hour treatment was "long enough for patients to achieve significant and sustained pain relief." She noted that the treatment was in a clinic setting and not under normal conditions of where a migraine would occur. Thus, in the clinic setting, electrodes and the device were placed correctly and ensured proper application of the treatment.
Besides being a nonpharmacologic alternative for patients intolerant of abortive medications, she suggested that eTNS might be used in an attack refractory to drugs and in status migrainosus.
At this point, she is planning a trial to see whether earlier treatment of an attack would be more efficacious than at 3 hours or more after the onset of an attack.
Although pain intensity was reduced by the active stimulation compared with the sham, Werner Becker, MD, University of Calgary, Alberta, Canada, noted that "Interestingly, the rescue medication, as they put it, was not less in the active group as compared to the sham. So people are still taking their pain killers or their acute medications, but nevertheless, they're having less pain, it would appear."
Many patients want to avoid medications and their side effects and thus may be interested in a neuromodulation therapy. However, "some patients, I think, can't tolerate this because it does involve a stimulation of the face, and I if recall correctly, there were some patients who couldn't enter [into the study] because they couldn't tolerate a trial stimulation because they were just too sensitive, too much allodynia," he told Medscape Medical News.
Dr Becker said a previous trial showed eTNS was beneficial for patients with episodic migraine, but the present trial recruited patients with episodic and chronic migraine, suggesting this population may be more severely affected by migraine.
When asked whether there is any reason to think that eTNS would be more effective than vagus nerve stimulation, he said, "You would think that stimulation of the trigeminal nerve would be more effective given that you're providing stimulation in the area where the pain actually comes from."
Dr Becker explained that eTNS stimulates a trigeminal branch to the somatic tissues of the skin and face as opposed to the actual neurons from the dura, but that the ones from the face are probably more intimately associated with the dural afferents.
"The vagus stimulation is stimulating other afferents and not dural afferents. Having said that, it's a mysterious business, and I guess you could say it's largely empirical," he said, suggesting that ultimately further studies will be needed.
People also do occipital nerve stimulation in headache disorders, the rationale being that those afferent fibers also go to the trigeminal nucleus caudalis and intermingle with the afferents of the head and dura, he noted.
The trigeminal ones would presumably be related even more closely to where the pain is coming from than the occipital nerve afferents or vagal afferents, "but in the brainstem these things are all interlinked," he said, "so I guess you can't really predict what would be more effective."
Dr Chou is on advisory boards of Amgen, Eli Lilly, Teva, Allergan, and Pernix; has research funding from Teva, Alder, and Capnia; and has received speaking honoraria from Medscape and Peerview (with educational grants from Teva). The study received funding from CEPHALY Technology. Dr Becker has disclosed no relevant financial relationships.