In 2011, I wrote an evaluation of a migraine treatment product that was just beginning to move across the Atlantic from Europe. Cefaly is a headband that delivers electrical stimulation externally to the major occipital and transgeminal nerves. The idea is that transcutaneous nerve stimulation can have similar results reported for more invasive treatments. However even the careful placement of electrodes directly on the nerves, while promising, is still in early stages of development. The reason for this second look at Cefaly is a news release from the US Food and Drug Administration announcing that STX-Med is now allowed to market their product in the US.
For Immediate Release: March 11, 2014 Media Inquiries: Jennifer Rodriguez, 301-796-8232, firstname.lastname@example.org Consumer Inquiries: 888-INFO-FDA FDA allows marketing of first medical device to prevent migraine headaches Today, the U.S. Food and Drug Administration allowed marketing of the first device as a preventative treatment for migraine headaches. This is also the first transcutaneous electrical nerve stimulation (TENS) device specifically authorized for use prior to the onset of pain. “Cefaly provides an alternative to medication for migraine prevention,” said Christy Foreman, director of the Office of Device Evaluation at the FDA’s Center for Devices and Radiological Health. “This may help patients who cannot tolerate current migraine medications for preventing migraines or treating attacks.” Migraine headaches are characterized by intense pulsing or throbbing pain in one area of the head, accompanied by nausea or vomiting and sensitivity to light and sound. A migraine can last from four to 72 hours when left untreated. According to the National Institutes of Health, these debilitating headaches affect approximately 10 percent of people worldwide and are three times more common in women than men. Cefaly is a small, portable, battery-powered, prescription device that resembles a plastic headband worn across the forehead and atop the ears. The user positions the device in the center of the forehead, just above the eyes, using a self-adhesive electrode. The device applies an electric current to the skin and underlying body tissues to stimulate branches of the trigeminal nerve, which has been associated with migraine headaches. The user may feel a tingling or massaging sensation where the electrode is applied. Cefaly is indicated for patients 18 years of age and older and should only be used once per day for 20 minutes. The FDA reviewed the data for Cefaly through the de novo premarket review pathway, a regulatory pathway for generally low- to moderate-risk medical devices that are not substantially equivalent to an already legally marketed device. The agency evaluated the safety and effectiveness of the device based on data from a clinical study conducted in Belgium involving 67 individuals who experienced more than two migraine headache attacks a month and who had not taken any medications to prevent migraines for three months prior to using Cefaly, as well as a patient satisfaction study of 2,313 Cefaly users in France and Belgium. The 67-person study showed that those who used Cefaly experienced significantly fewer days with migraines per month and used less migraine attack medication than those who used a placebo device. The device did not completely prevent migraines and did not reduce the intensity of migraines that did occur. The patient satisfaction study showed that a little more than 53 percent of patients were satisfied with Cefaly treatment and willing to buy the device for continued use. The most commonly reported complaints were dislike of the feeling and not wanting to continue using the device, sleepiness during the treatment session, and headache after the treatment session. No serious adverse events occurred during either study. Cefaly is manufactured by STX-Med in Herstal, Liege, Belgium. For more information: FDA: Medical Devices NIH: NINDS Migraine Information Page
The important thing to note here is that Cefaly has been approved through the “de novo premarket review pathway, a regulatory pathway for generally low- to moderate-risk medical devices”. The safety study referenced by STX-Med for approval involved over 2,000 patients of which only 4.3% reported any adverse reactions, all of which were mild and reversible following discontinuation of treatment. This study did not examine the effectiveness of the headset in any way other than a vague outcome of ‘patient satisfaction’.
The study that did involve efficacy had only 67 patients in the trial, but some of the outcomes showed promise. The researchers compared sham neurostimulation against the standard Cefaly stimulation. There was no control without a device.
The STS generates biphasic rectangular impulses with an electrical mean equal to zero and the following characteristics: pulse width 30 µs for sham and 250 µs for verum, frequency 1 Hz for sham and 60 Hz for verum, maximum intensity 1 mA for sham and 16 mA for verum. The daily sham or verum neurostimulation sessions lasted 20 minutes.
Patients maintained a diary and recorded headache frequency and severity.
Primary outcome measures were 1) change in monthly migraine days between the run-in month and the third month of treatment; and 2) percentage of “responders,” i.e., of subjects having at least 50% reduction of monthly migraine days between run-in and third month of treatment.
Secondary outcome measures were 1) change in monthly migraine days between run-in and the average 3 months of treatment; 2) change in monthly migraine attack frequency; 3) change in monthly frequency of any headache; 4) change in mean headache severity per migraine day; 5) change in monthly acute antimigraine drug use and in associated symptoms per migraine headache between run-in and third month of treatment; and 6) percentage of patients stating at the end of the trial that they are very satisfied, moderately satisfied, or not satisfied with the treatment.
My statistics are rusty, but the number of total comparisons would increase the possibility of a false positive, and the inclusion of study dropouts using data up to the time they left the study seems questionable to me. Perhaps someone with a grasp of the relevant stats could leave a comment to help clarify the appropriateness of the analysis.
There were a number of reasons that patients were excluded from the study:
Exclusion criteria were use of a preventive antimigraine treatment in the previous 3 months, failure on well-conducted preventive drug treatments, medication overuse headache (ICHD-II 8.2), frequent/chronic tension-type headache (ICHD-II 2.2/2.3), and other severe neurologic or psychiatric disorders.
In the end, the number of migraines was decreased in the active treatment group, as was the amount of medication required. There was also an increase in the number of patients who reported a 50% decrease in attacks.
A third study describing the sedative effect of Cefaly used a slightly different protocol in an attempt to control for the patient’s ability to sense the electric current by using controls and sham neurostimulation.
We performed a double-blind crossover sham-controlled study of 30 subjects to assess the effect on vigilance of different protocols of supra-orbital TNS. Each subject was tested in 4 different experimental conditions: without neurostimulation device (blank control: BC), with a sham neurostimulation (Sham control: SC), with a low frequency neurostimulation (LFN) and with a high frequency neurostimulation (HFN)
Results are compatible with decreased vigilance and arousal studies, but show no indication of inducing or improving sleep. Sedation may help some patients with migraine, but decreased arousal during sleep has been associated with sufferers.
The primary Cefaly site lists only the 3 studies described here, while the Canadian site, at least at the time of this writing, still contains the entire list of irrelevant studies with the misleading headings I discussed in my previous article. I’m not going to comment on the testimonials except to say that my degree of skeptism of any treatment is directly proportional to the number of testimonials used in advertising.
These studies show the possibility of Cefaly as a partial prophylactic for some types of migraines, but but no indication it is useful as a treatment for an ongoing attack.
So, the question remains, is Cefaly worth the price? The cost on the Cefaly Canada site is $349.00 + taxes and shipping (total=$388.49). A pack of 3 extra electrodes is $24.99 ($31.49 total). Each electrode is supposed to last for 15-30 uses, so the additional cost of the electrodes could be anywhere from $127 to $255 per year. Cefaly seems to be well tolerated by most users, at least in the short term. However, it is not an insignificant cost for something that may have no effect at all. It would be interesting to see how many people are still using it 3 or 4 years later.
The decrease in requirement for medication is intriguing on a cost basis, and also the potential for limiting the possible side-effects. There is a wide range of medications used to treat migraines, and each comes with it’s own side-effect profile; a fairly comprehensive list can be found on the Rx List site. As the study above noted, Cefaly is not considered a useful treatment for an ongoing attack, so for those who require acute treatment, medication will not be eliminated. Cefaly is also much less invasive than implanted electrodes, and it might be worth considering before undergoing surgery.
Migraine is a complex disorder with varied triggers and there is no single treatment that could ever hope to eliminate all attacks, and I do understand that for anyone who suffers from chronic pain that any hope can be worth a try and it appears that the risks of using Cefaly are mostly financial. It is possible that Cefaly might help any given individual, but each person should take these and other aspects into consideration.