Neurostimulation for Migraine Attacks

New device treats migraines after they start

migraine
JGI/Jamie Grill / Getty Images  

Migraines are difficult to treat. Anti-migraine treatments have adverse effects and are often insufficiently effective. Moreover, when taken regularly, anti-migraine medications can result in a headache "chronification," or a headache worsening. Consequently, there’s been great interest in developing non-pharmacological treatments for a migraine, including neurostimulation (i.e., nerve stimulation).

The Cefaly device is an external trigeminal nerve stimulator (e-TNS) that sends currents through an electrode placed on the forehead. It works by stimulating the ophthalmic nerve, which is a branch of the trigeminal nerve. The Cefaly device was previously approved by the FDA for migraine prevention. In December 2017, it was released for the treatment of acute migraines and can be used after a migraine starts.

What Is the Cefaly Device?

The Cefaly device is a headband that generates a constant current using two AAA batteries. The current is applied across the skin of the forehead, using a self-adhesive electrode. The Cefaly stimulates the supratrochlear and supraorbital branches of the ophthalmic nerve, which in turn is a branch of the trigeminal nerve. The trigeminal nerve plays a big role in migraine headaches.

Cefaly comes in three models: Cefaly Acute, Cefaly Prevent, and Cefaly Dual. Cefaly Acute treats acute migraine attacks. Cefaly Prevent is used to prevent migraines. And Cefaly Dual has settings for both.

The Cefaly Acute provides a high-intensity, 60-minute stimulation session. The Cefaly Prevent is low frequency and can be used daily.

According to its makers, the Cefaly device gradually increases in intensity during the first 14 minutes of use. During this period, if the current becomes too intense, you can press a button to stabilize the intensity and halt any further increase in intensity.

The manufacturer does list contraindications on its website, which applies to people with:

  • an implanted metallic or electronic device in the head
  • suffering from the pain of unknown origin
  • a cardiac pacemaker or implanted or wearable defibrillator, which may cause interference with pacing, electric shock, or death

The mode of action by which e-TNS works is unclear. Initially, experts postulated that neurostimulation blocks ascending impulses in the pain pathway. However, this hypothesis was not supported by research findings. Conversely, it’s been suggested that e-TNS alter pain control in a top-down fashion.

The FDA approval for Cefaly as a prophylactic treatment was based on results of two European trials: the PREMICE Trial and the European Post-Marketing Surveillance Study.

The PREMICE Trial

The PREMICE Trial was a randomized controlled trial of Cefaly, which was conducted between 2009 and 2011 by the Belgian Headache Society. This study was a prospective, or long-term, study that included 67 patients with at least two migraine attacks each month.

In this trial, there was a one-month baseline period before participants were assigned to either real or sham (i.e., fake) stimulation. The treatment period lasted for three months.

Here are the results of the study:

  • Those receiving Cefaly treatment experienced a significant decline in both a migraine and headache days by the third month of treatment.
  • Patients who received Cefaly treatment experienced 29.7 percent fewer migraine days and 32.3 percent fewer headache days.
  • In the control or sham, group, the reductions in migraine days and headache days was 4.9 percent and 3.4 percent, respectively.
  • In the experimental group, or those receiving Cefaly treatment, 38.2 percent of patients experienced at least a 50 percent reduction in monthly migraine days.
  • In the control group, 12.1 percent of participants experienced at least a 50 percent reduction in monthly migraine days.
  • Overall, there was a statistically significant reduction in migraine days in the experimental group.
  • Although not statistically significant, those receiving Cefaly treatment did report a reduction in the severity of migraines.
  • Those participants using Cefaly needed 36.7 percent less medication to treat migraine headaches.
  • In those receiving sham treatment, there was a 0.4 percent increase in anti-migraine medication intake.
  • There were no negative side effects in those using Cefaly.
  • Cefaly may be most beneficial for people with more frequent migraines, or greater than four a month (i.e., seven migraine days). Apparently, more research is being done to examine this specific patient population.

The European Post-Marketing Surveillance Study

A registry was established for all patients who obtained the Cefaly device between September 2009 and June 2012. Most of these consumers lived in France and Belgium. After having used the device between 40 and 80 days, these patients were asked to participate in a survey assessing satisfaction and concerns about negative side effects.

The results of this post-marketing study showed that about 53 percent of patients were satisfied with the treatment and wanted to continue using the device. About 4 percent of patients were dissatisfied with the device. None of these complaints involved serious adverse effects. Specifically, these consumers complained of the sensation caused by the device (i.e., "tingling"), sleepiness during the session, and headache after the session.

Cefaly for a Migraine Attack

Based on the results of a randomized, placebo control trial called ACME (Acute Treatment of Migraine with External trigeminal nerve stimulation), in December 2017, the FDA further approved Cefaly for the treatment of migraine attacks as they occur. With these increased clinical indications, the number of people with migraines who would benefit from Cefaly has increased 10-fold. In this study, there was a 65 percent reduction in the pain intensity of migraines, and 32 percent of participants were pain-free within an hour.

Results from an open-label trial examining the safety and efficacy of Cefaly for the treatment of an acute migraine were published in the journal Neuromodulation in October 2017. In this study, Chou and colleagues examined the use of Cefaly in 30 patients who were experiencing migraines either with or without aura. To be included in the study, these patients must have had a migraine attack lasting at least three hours. Furthermore, these people must not have taken any medication for the migraine attack.

Treatment with Cefaly was given for one hour. At both one and two hours after the start of treatment, the participants were asked to rate their pain using pain scales.

According to Chou and co-authors, here are the results of their Cefaly study:

"With regards to efficacy, mean pain intensity was significantly reduced by 57.0 percent after the one-hour treatment and by 52.8 percent at two hours. The similar rate at the two time points indicates that pain reduction is well-maintained for at least an hour after the end of the neurostimulation. The percentage of patients not using rescue medication was 100 percent after two hours and 65.4 percent after 24 hours. The proportion of patients not taking rescue medication within 24 hours in placebo groups for pharmacologic acute migraine treatment trials is usually reported to be around 32 percent."

Of note, “rescue medications” refer to medications taken when a first-line medication fails to help. In this study, if the Cefaly session failed, then participants would take rescue medications. Intake of the rescue medications was recorded at two hours and 24 hours.

In addition to effectively treating migraine attacks, Chou and colleagues observed no adverse events, and none of the participants complained about the treatment.

It’s difficult to compare the efficacy of Cefaly with medications used to treat a migraine because of differences in trial designs between studies. Nonetheless, using the same pain scale, a separate study found that one hour after taking the NSAID diclofenac (Voltaren), patients reported a 26.8 percent reduction in pain scores compared with a 17.1 percent reduction in migraine pain for those taking sumatriptan, and a 52.7 percent reduction in those receiving a Cefaly session.

With regard to the intake of rescue medications, other research suggests that between 20 percent and 34 percent of people need to take a rescue medication between two and 24 hours after taking a triptan. Furthermore, on average, 37 percent of people who take an NSAID need to take rescue medications. Whereas, 34.6 percent of patients receiving a Cefaly session need to take rescue medications. 

Ultimately, it appears that Cefaly works as well as other treatments for migraine headaches including triptans and NSAIDs. Unlike these other medications, however, Cefaly doesn’t have any serious adverse effects. Moreover, the researchers suggest that the Cefaly device could be even more effective if used earlier than three hours into an attack.

More Information About Migraines

About 12 percent of Americans develop migraines. Migraines are three times more common in women. According to the Global Burden of Disease Study 2013, migraines are the sixth most disabling illness worldwide and result in substantial impairment to quality of life.

Migraines occur in attacks of moderate to severe pain. The quality of the pain is pulsing or throbbing—usually affecting only one side of the head. During a migraine attack, people experience heightened sensitivity to light and sound. Migraine sufferers may also experience nausea and vomiting. 

Some people experience sensory disturbance either before or during a migraine attack. This sensory disturbance is called an aura. These disturbances can be visual, such as flashing lights or blind spots. They can also manifest as tingling in the hands or face.

Migraine triggers include:

  • Stress
  • Anxiety
  • Lack of sleep
  • Exposure to light
  • Hormonal changes

The management of migraines can be either acute or preventive. Acute treatments are used to stop a migraine attack and restore normal functioning. Preventive management aims to modify attack frequency and severity.

Drugs used for acute treatments for a migraine include:

  • NSAIDs
  • Analgesic
  • Triptans

Here are preventive treatments for a migraine:

  • Beta-blockers (e.g., metoprolol, propranolol, bisoprolol, and candesartan)
  • Calcium channel blockers (e.g., flunarizine and verapamil)
  • Anticonvulsants (e.g., topiramate and valproate)

Nutraceuticals, including riboflavin, coenzyme Q10, and magnesium, have lower efficacy in preventing migraine attacks.

Writing in Cephalalgia, Dodick, and Martin comment on the adverse effects of triptans:

"While seemingly a homogenous group of drugs, results from a meta-analysis reveal significant differences in efficacy and tolerability among oral triptans. The incidence of drug-related central nervous system (CNS) side effects with some triptans is as high as 15 percent and may be associated with functional impairment and reduced productivity. The occurrence of adverse events associated with triptans in general, and CNS side effects in particular, may lead to a delay in initiating or even avoidance of an otherwise effective treatment."