For patients and families

sTMS does not cause discomfort and can be used for both prevention and for treating migraines acutely. However, it is a device that requires storage and charging and is relatively large, which can preclude use in those who travel frequently. It is also loud during use which may be problematic if prominent noise sensitivity is present. Practically, it is a reasonable option for those seeking nonmedication treatments and who prefer a device that can treat both acute attacks and be used for prevention. It is also ideal for someone who is sensitive to adhesives or gels or prefers a device that they don’t have to “wear” and won’t be able to feel on their head/neck during use.

For providers

Acute use efficacy was established in an adult trial that showed a 17% reduction in 2-h pain freedom with sTMS use compared to the sham device (39% vs. 22%, p = 0.179). The open label ESPOUSE trial evaluated sTMS for migraine prevention and found that after 3 months of use, 46% of participants reported a greater than 50% reduction in the number of headache days per month and there was on average 2.8 less headaches days per month with use. In pediatrics, a small open label prospective trial ( n = 12) primarily looking at safety also noted an improvement in headache days from 13.3 at baseline to 8.8 after 3 months of daily use, an absolute reduction of − 4.5 days.

Typically, this device is recommended to be used for 4 pulses in the morning and 4 pulses at night (2 pulses, wait 15 min, 2 pulses) for prevention. Pediatric trial data however, seems to suggest that it is safe and just as effective to remove the 15 min pause between the 2 pulses. For acute treatment, it is recommended to give three sequential pulses at onset of migraine, wait 15 min and then if needed treat again with 3 additional pulses. This can be repeated a 3rd time for a total of 9 acute pulses over a 30-min period.

There does not appear to be any significant or serious side effects with use of the device. Reported side effects from trials were seen in 13%–29% and included: dizziness or light-headedness, discomfort from noise, application site tenderness or tingling, and headache. sTMS is contraindicated in those with epilepsy or a family history of epilepsy or in those with a history of stroke. Caution should be used in those with recent head injury or if a patient is on medications that can “lower” seizure threshold. It should not be used in those with any implanted metal devices in the head, neck and upper body including vagal nerve stimulators, pacemakers, or implanted cardioverter defibrillator (ICD). A full list of metal containing implants is listed on the company website. It should not be used in those with suspected or diagnosed heart conditions. Dental fillings appear to be safe. It has not been adequately studied in those who are pregnant or < 12 years of age (Label insert, eneura.com ).

For patients and families

The tSNS device needs to be worn for 20 min daily for preventive use and can be used for up to 1 hour for the acute treatment of migraine. Patients often find it helpful to practice cognitive behavioral therapy, mindfulness, or biofeedback during the “downtime” while using the device. The tSNS device is helpful for those seeking non medication alternatives and ideal for those who like the idea of using the time required for treatment to practice various complementary medicine techniques. Limitations to use are that it does require one to spend 20 min daily with something affixed to their forehead, which may be unrealistic for some. Other limitations are that it may cause tingling in the forehead and it uses an adhesive that may cause a hyper-sensitivity reaction in vulnerable patients or in those with allergies.

For providers

tSNS was initially studied in a pilot study ( n = 10) in patients with episodic migraine and was found to be effective in reducing monthly attack frequency by 1.3 days. This led to a larger trial for migraine prevention in adults called PREMICE. In this randomized, sham-controlled trial of adult patients with episodic migraine ( n = 59) who used the device for 20 min a day for 3 months, 38.2% had a 50% reduction in migraine days per month vs. 12.1% in the sham group ( p = 0.023), a therapeutic gain of 26.1%. Migraine days per month reduced by 2.06 days in the active group and 0.32 days in the sham group, (6.94 to 4.88 for tSNS vs. 6.54 to 6.22 for sham) but this was not a statistically significant result. The authors also noted a 36.7% reduction in acute medication use (vs. sham that experienced a 0.4% increase). In a trial evaluating the acute use of tSNS in migraine ( n = 109), 63% of patients achieved > 50% relief at 1 h (vs. 31% in the sham group, p = 0.0017) and 29% of patients reported pain freedom at 1 h (vs. 6% in the sham group, p = 0.0016). In chronic migraine, tSNS for both prevention and acute treatment also seems to be favorable. In an open-label prevention trial in chronic migraine ( n = 19), after 4 months of use 35% of patients had a 50% reduction in both headache days and acute medication use. Mean reduction of headache days was 57.9%. In an open-label acute treatment trial in adults with chronic migraine ( n = 23), 44% were pain free at 1 h with use of tSNS.

The device is overall well tolerated with no serious adverse events reported. In a large post-marketing survey of 2313 users, 4.3% reported minor side effects including tingling in the area of the device, pain or intolerance, allergic reaction to device or gel, fatigue or headache. No contraindication is noted for use in pregnancy. Contraindications include any implanted metallic devices or electronic devices, pacemakers, or ICD. Adherence may be a problematic for some considering tSNS, as compliance rates in one trial were noted to be only ~ 60%.

For patients and families

This is a smaller device than the two mentioned above and may be ideal for those seeking a quick, nontablet-based treatment, but who need a smaller device to accommodate their lifestyle. It does, however, require the use of a gel at the application site and three-times-per day use for migraine prevention which may limit its convenience.

For providers

Efficacy was established for preventive use in chronic migraine in the prospective, randomized sham-controlled EVENT trial ( n = 59) where a nonsignificant reduction in headaches days was seen in the nVNS group vs. sham (− 1.4 days vs. − 0.2 days). During the open-label extension of this trial, after 8 months of use, there was a significant mean change from baseline in headache days of − 7.9 ( p ≤ 0.01). Acute treatment was evaluated in the PRESTO trial ( n = 248) with 30-min pain freedom rates of 12.7% in the nVNS group vs. 4.2% in the sham group ( p = 0.012). This extended to 21% vs. 10% by 60 min ( p = 0.023) and 30.4% vs. 19.7% at 120 min ( p = 0.067).

nVNS use for migraine prevention involves three treatments (morning, mid-day and night. Each treatment consists of two consecutive 2-min stimulations (2-2-2)). For acute migraine treatment, it is used for two consecutive 2-min stimulations, followed by a 20-min wait and then if pain persists, two further 2-min stimulations and then, after a 2-h wait, if required a third treatment consisting of two consecutive 2-min stimulations (2-(20 min)-2-(2 h)-2) (package insert, gammacore.com ).

The most commonly reported side effects included: neck discomfort and/or shoulder twitching/pain, facial/lip pulling, twitching or drooping, voice change, dizziness, and application site pain or skin irritation. Despite vagal involvement in cardiac control , animal data suggests that the use of nVNS does not seem to effect cardiac function, however, it should not be used in those with a history of hypertension, hypotension, bradycardia, or tachycardia. It should not be used if a person has an implantable medical device (pacemakers/defibrillators, hearing aid implant or any other implanted electronic medical device), an implanted metallic device in or near the neck, or if one is using another device at the same time (TENS unit, muscle stimulator, or mobile phone). Additionally, it should not be used if someone has been diagnosed with carotid atherosclerosis or has a history of cervical vagotomy. Use in children < 12 and pregnancy has not been evaluated (package insert, gammacore.com ).

For patients and families

The REN device is an acute use-only treatment device for migraine. It is a relatively affordable nonmedication option for the acute treatment of migraine that can be worn discretely under clothing and used at any time of the day. It connects remotely via the user’s smartphone and doesn’t require any wires, adhesives or gels for use once it is in place.

For providers

The first pilot trial for acute migraine treatment ( n = 71) showed pain reduction in 58% vs. 24% for placebo ( p = 0.02) and pain freedom in 30% vs. 6% ( p = 0.004). In larger follow-up prospective acute trial in episodic migraine ( n = 252), significantly higher pain freedom was seen in the treatment vs. sham group (37.4% vs. 18.4%, p = 0.03) at 2-h and significantly higher pain reduction was seen in the treatment vs. sham group (66.7% vs. 38.8%, p < 0.001). In chronic migraine, an open label pilot study ( n = 42) showed that 73.7% of participants achieved pain relief at 2-h in at least 50% of their treated attacks and 26.3% had pain freedom in at least 50% of treated attacks at 2-h. At 2-h, mean pain relief across subjects was 59.3% and mean pain freedom across subjects was 25.9%. In a follow up larger “real world” trial ( n = 4725), pain relief was seen in 58.9% in those seen by headache specialists and 74.2% of those seen by nonheadache specialists in at least 50% of treated attacks. Pain freedom was seen in 20% of those in the headache specialists group and 35.6% of those in the nonheadache specialists group.

The REN device appears to be very safe with device related adverse events occurring in < 2% and the only consistently reported side effects being tingling, pain, redness or burning at the site of the device.