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All Non-Invasive Neuromodulation Devices for Migraine Treatment

Posted on October 27 2025, By: Cerebral Torque

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Non-Invasive Neuromodulation Devices for Migraine Treatment

A comprehensive review of FDA-cleared and CE-marked devices based on International Headache Society evidence-based guidelines

Introduction

Non-invasive neuromodulation offers an emerging treatment option for headache disorders. The International Neuromodulation Society defines therapeutic neuromodulation as "the alteration of nerve activity through targeted delivery of a stimulus, such as electrical stimulation or chemical agents, to specific neurological sites in the body."

Unlike invasive devices that require implantation, non-invasive neuromodulation can be applied topically via various modalities, including electrical stimulation. This non-invasive approach offers minimal side effects, eliminates surgical risks, provides greater accessibility to treat migraine attacks early, and allows treatment discontinuation without permanent consequences.

Currently, six non-invasive neuromodulation devices have received FDA clearance in the United States, while eight have obtained CE markings in Europe for treating various headache disorders based on different modes of action.

6
FDA-Cleared
Devices approved in the United States
8
CE-Marked
Devices approved in Europe
15
Clinical Trials
Randomized controlled trials reviewed

Why Consider Neuromodulation Devices?

Patients may choose non-invasive neuromodulation for acute or preventive migraine treatment based on personal preference or when pharmacological therapies prove ineffective, cause adverse effects, or are contraindicated. These devices can serve as standalone treatments or complement pharmacological interventions, potentially enhancing efficacy or reducing acute medication use.

Overview of Available Devices

The following table summarizes all FDA-cleared and CE-marked non-invasive neuromodulation devices for migraine treatment:

Device Age Mode of Stimulation Treatment Location Indications
SAVI Dual
FDA + CE		 ≥12 years Single pulse transcranial magnetic stimulation Occipital region • Acute: 4 pulses at onset
• Preventive: 4 pulses morning/evening
Cefaly
FDA + CE		 ≥18 years Supraorbital trigeminal nerve stimulation Forehead • Acute: 60 min ACUTE program
• Preventive: 20 min daily (episodic migraine only)
gammaCore Sapphire
FDA + CE		 ≥12 years Transcutaneous vagus nerve stimulation Side of neck • Acute: 2 min bilateral at onset
• Preventive: 2 min bilateral twice daily
HeadaTerm
FDA + CE		 ≥18 years Predicate device to Cefaly PREVENT Forehead • Acute: Not specified
• Preventive: 60 min total per day (episodic migraine only)
Nerivio
FDA + CE		 ≥8 years Transcutaneous electrical stimulation (arm) Upper arm • Acute: 45 min at symptom onset
• Preventive: 45 min every other day
Relivion
FDA + CE		 ≥18 years External concurrent occipital and trigeminal neurostimulation Forehead and occiput • Acute: 20-60 min at headache onset
• Preventive: Not specified
tVNS
CE only		 ≥3 years Transauricular vagus nerve stimulation Cymba conchae (ear) • Acute: Not specified
• Preventive: 4 hours per day
Ozilia
CE only		 ≥18 years Intranasal kinetic oscillation stimulation Each nostril • Acute: Not specified
• Preventive: 10 min each nostril weekly (chronic migraine only)

SAVI Dual

SAVI Dual Device

Mechanism of Action

SAVI Dual delivers single-pulse transcranial magnetic stimulation (TMS) to the occipital region. The device works by interrupting cortical spreading depression and modulating thalamocortical pathways, targeting key mechanisms involved in migraine pathophysiology.4,5

Treatment Protocol

  • Acute Treatment: 4 sequential pulses (30 seconds apart) at the onset of an attack
  • Preventive Treatment: 4 pulses each morning and evening
  • Approved Age: ≥12 years
  • Location: Occipital region (back of head)

Evidence Summary

Acute Treatment:

In adult patients with episodic migraine with aura, SAVI Dual (2 pulses, 30 seconds apart) showed superiority over inactive sham for acute migraine treatment. A single randomized controlled trial (treating ≥1 attack, within 1 hour of aura onset) demonstrated benefits including:30

  • Pain freedom at 2 hours (primary endpoint): OR 2.28 (95% CI 1.15-4.52)
  • Sustained pain freedom at 24 hours: OR 2.20 (95% CI 1.03-4.70)
  • Adverse event rate comparable to sham group
IHS Recommendation - Acute Treatment

Weak in favor (↑)
Quality of evidence: Low (⊕⊕⊝⊝)

The panel conditionally recommends SAVI Dual for the treatment of acute migraine attacks in adult patients with episodic migraine with aura.

Preventive Treatment:

No randomized controlled trial met the eligibility criteria for preventive treatment assessment.

IHS Recommendation - Prevention

No evidence-based recommendation available due to lack of eligible randomized controlled trials.

Expert Consensus Suggestions

  1. SAVI Dual can be an option for the treatment of acute migraine attacks in patients with episodic or chronic migraine with/without aura31
  2. SAVI Dual can be an option for preventive treatment in patients with migraine, with or without medication overuse headache, in adults, adolescents, and pregnant patients31-36

Practical Considerations

  • Advantages: Non-invasive, no systemic side effects, safe for adolescents and pregnant patients
  • Limitations: High device cost, limited accessibility, requires proper technique for optimal placement
  • Safety: Generally well tolerated with minimal adverse events

Cefaly

Cefaly Device

Mechanism of Action

Cefaly delivers transcutaneous electrical supraorbital trigeminal nerve stimulation. The device works through peripheral "gate control" mechanisms and central effects, altering activity in the anterior cingulate cortex and thalamus.6,7

Treatment Protocol

  • Acute Treatment: 60 minutes using ACUTE program at the onset of migraine
  • Preventive Treatment: 20 minutes daily using PREVENT program (episodic migraine only)
  • Approved Age: ≥18 years
  • Location: Forehead (supraorbital region)

Evidence Summary

Acute Treatment:

In adult patients with episodic migraine with and without aura, Cefaly showed superiority over active sham for acute treatment. Two randomized controlled trials (ACME: 1-hour stimulation for headache lasting >3 hours; TEAM: 2-hour stimulation within 4 hours of onset) demonstrated moderate effects:37,38

  • Pain freedom at 2 hours: OR 1.62 (95% CI 1.09-2.39)
  • Pain relief at 2 hours: OR 1.85 (95% CI 1.30-2.64)
  • Sustained pain freedom at 24 hours: OR 1.66 (95% CI 1.08-2.54)
  • Pain intensity difference at 2 hours: MD 1.02 (95% CI 1.82-0.22)
IHS Recommendation - Acute Treatment

Weak in favor (↑)
Quality of evidence: Moderate (⊕⊕⊕⊝)

The panel conditionally recommends the use of Cefaly for the treatment of acute migraine attacks in adult patients with episodic migraine.

Preventive Treatment:

In adult patients with episodic migraine, Cefaly (20 minutes daily) showed probable superiority over active sham. A single randomized controlled trial did not meet one of its co-primary endpoints (monthly migraine days reduction: MD 1.74, 95% CI −0.32 to 3.8), but the 50% responder rate favored Cefaly (OR 4.49, 95% CI 1.28-15.72).42

IHS Recommendation - Prevention

Weak in favor (↑)
Quality of evidence: Very low (⊕⊝⊝⊝)

The panel conditionally recommends the use of Cefaly for preventive migraine treatment in adult patients with episodic migraine.

Expert Consensus Suggestions

  1. Cefaly can be an option for the acute treatment of pediatric migraine and vestibular migraine39,40
  2. Cefaly can be an option for the treatment of acute migraine attacks in adults with chronic migraine41
  3. Cefaly can be an option for preventive treatment of chronic migraine and medication overuse headache in pediatric and adult populations43-48

Practical Considerations

  • Advantages: Available without prescription in many countries, good safety profile, easy to use
  • Limitations: Longer treatment duration may be needed for acute use (2 hours vs. 1 hour)
  • Safety: Adverse events infrequent and minor, primarily topical sensations

gammaCore Sapphire

gammaCore Sapphire Device

Mechanism of Action

gammaCore Sapphire delivers transcutaneous vagus nerve stimulation in the neck. The device works by inhibiting pain networks, suppressing nociception in the trigeminal cervical complex, and exerting anti-inflammatory effects.8,9

Treatment Protocol

  • Acute Treatment: 2 minutes of unilateral stimulation on each side at the onset of attack
  • Preventive Treatment: 2 minutes of unilateral stimulation on each side, twice daily
  • Approved Age: ≥12 years
  • Location: Side of the neck (over carotid artery)

Evidence Summary

Acute Treatment:

In adult patients with episodic migraine with/without aura, gammaCore Sapphire (2 minutes on each side) may not be superior to active sham for acute treatment. The randomized controlled trial (treating ≥1 attack within 20 minutes of onset, including mild headache) did not meet its primary endpoint (pain freedom for first-treated attack at 2 hours: 30.4% vs. 19.7%, p=0.067), although significant benefits were seen at 30/60 minutes (pain freedom) and 2 hours (pain relief).49

IHS Recommendation - Acute Treatment

No recommendation
Quality of evidence: Low (⊕⊕⊝⊝)

There were no solid efficacy data to recommend the use of gammaCore Sapphire for the treatment of acute migraine attacks.

Preventive Treatment:

In adult patients with migraine, gammaCore Sapphire (2 minutes twice, three times daily) showed superiority over sham for preventive treatment. Two randomized controlled trials (PREMIUM, PREMIUM II) demonstrated:58,59

  • Mean monthly migraine days reduction: MD 0.72 (95% CI 0.31-1.14)
  • Mean monthly headache days reduction: MD 0.91 (95% CI 0.43-1.40)
  • 50% responder rate: OR 1.73 (95% CI 1.11-2.69)
  • Monthly acute medication use days: MD 0.81 (95% CI 0.02-1.61)
IHS Recommendation - Prevention

Weak in favor (↑)
Quality of evidence: Moderate (⊕⊕⊕⊝)

The panel conditionally recommends the use of gammaCore Sapphire for preventive treatment of episodic/chronic migraine in adult patients with migraine, especially if they can maintain treatment adherence.

Expert Consensus Suggestions

  1. The gammaCore Sapphire can be an option for the treatment of acute migraine attacks and associated vertigo and nystagmus in patients with vestibular migraine49-52
  2. The gammaCore Sapphire can be an option for the treatment of acute migraine attacks in adolescents53
  3. The gammaCore Sapphire can be an option for the treatment of acute migraine attacks in patients with chronic migraine, although perhaps to a lesser degree than in episodic migraine and probably ineffective in refractory chronic migraine54,55
  4. The gammaCore Sapphire can be an option for the treatment of acute migraine attacks in patients with medication overuse headache56,57
  5. The gammaCore Sapphire can be an option for preventive treatment of menstrual and menstrually-related migraine when used perimenstrually61
  6. The gammaCore Sapphire can be an option for preventive treatment in adult patients with chronic migraine60

Practical Considerations

  • Advantages: Non-invasive, safe for adolescents, functionally similar devices available over-the-counter as wellness products
  • Limitations: High device cost, accessibility issues, adherence-dependent efficacy for prevention
  • Safety: Adverse events generally mild-moderate, few withdrawals due to adverse events

HeadaTerm

HeadaTerm Device

Mechanism of Action

HeadaTerm is shown to be substantially equivalent to Cefaly PREVENTIVE. It delivers supraorbital trigeminal nerve stimulation with similar mechanisms of action involving peripheral "gate control" mechanisms and central effects.

Treatment Protocol

  • Acute Treatment: Not specified
  • Preventive Treatment: Accumulate a total of 60 minutes per day (episodic migraine only)
  • Approved Age: ≥18 years
  • Location: Forehead

Evidence Summary

Acute Treatment:

In the one randomized controlled trial reviewed, there were no eligible outcome data to assess the use of HeadaTerm for acute migraine treatment.62

IHS Recommendation - Acute Treatment

No recommendation

No evidence-based recommendation available.

Preventive Treatment:

No randomized controlled trial met the eligibility criteria for preventive treatment assessment.

IHS Recommendation - Prevention

No recommendation

No evidence-based recommendation available.

Expert Consensus Suggestions

  1. HeadaTerm can be an option for treatment of acute migraine attacks in adult patients with episodic migraine62
  2. Based on its status as a predicate device to Cefaly PREVENTIVE, HeadaTerm can be an option for preventive migraine treatment

Practical Considerations

  • Advantages: Substantially equivalent to well-studied Cefaly device, non-invasive
  • Limitations: Limited clinical trial data specific to HeadaTerm, device accessibility varies
  • Safety: Expected to be similar to Cefaly based on substantial equivalence

Nerivio

Nerivio Device

Mechanism of Action

Nerivio delivers transcutaneous electrical stimulation to the upper arm skin, activating endogenous analgesia through a pain-inhibit-pain phenomenon. Remote stimulation activates the descending pain inhibitory pathway.10,11

Treatment Protocol

  • Acute Treatment: 45 minutes as soon as migraine symptoms start
  • Preventive Treatment: 45 minutes every other day
  • Approved Age: ≥8 years (lowest age among all devices)
  • Location: Upper arm

Evidence Summary

Acute Treatment:

In adult patients with episodic migraine with or without aura, Nerivio may be superior to active sham for acute treatment. Two randomized controlled trials (2017 trial with 25-minute stimulation was terminated early; 2019 trial with 30/45-minute stimulation) showed:10,63

  • Pain relief at 2 hours: OR 2.65 (95% CI 1.61-4.38)
  • Pain freedom at 2 hours (2019 study): OR 2.64 (95% CI 1.39-5.02)
  • Device-related adverse events primarily topical issues, no serious adverse events
IHS Recommendation - Acute Treatment

Weak in favor (↑)
Quality of evidence: Very low (⊕⊝⊝⊝)

The panel conditionally recommends the use of Nerivio for the treatment of acute migraine attacks in adult patients with episodic migraine.

Preventive Treatment:

A double-blind, randomized, placebo-controlled trial of Nerivio 45 minutes every other day for eight weeks showed significant benefits. Of 248 participants (130 with chronic migraine), 179 (92 with chronic migraine) qualified for modified intention-to-treat analysis:73

  • Monthly migraine days reduction: 4.0±4.0 vs. 1.3±4.0 (therapeutic gain 2.7, 95% CI 1.5-3.9, p<0.001)
  • HIT-6 score change: 0.8 (95% CI −1.0 to 2.5, non-significant)
  • MSQ score change: −1.1 (95% CI −5.0 to 2.9, non-significant)
  • Treatment adherence high: ~90% completed >75% of treatments
IHS Recommendation - Prevention

Weak in favor (↑)
Quality of evidence: Very low (⊕⊝⊝⊝)

The panel conditionally recommends the use of Nerivio for preventive treatment of episodic/chronic migraine in adult patients with migraine.

Expert Consensus Suggestions

  1. Nerivio can be an option for the treatment of acute migraine attacks in pregnant women or patients with menstrually-related migraine65,66
  2. Nerivio can be an option for the treatment of acute migraine attacks in pediatric patients (≥8 years old)67-70
  3. Nerivio can be an option for the treatment of acute migraine attacks in adults with chronic migraine71,72
  4. Nerivio can be used for managing medication overuse headache73,74
  5. Nerivio can be combined with behavioral intervention75
  6. Nerivio can be an option for preventive migraine treatment in adolescents77

Practical Considerations

  • Advantages: Safe for children as young as 8 years, insurance coverage available for some payers in the US, wearable and portable
  • Limitations: Device accessibility outside the US, longer stimulation duration (45 minutes)
  • Safety: Device-related adverse events primarily topical issues at application site

Relivion

Relivion Device

Mechanism of Action

Relivion delivers external concurrent occipital and trigeminal neurostimulation (eCOT-NS). The device modulates the trigeminal cervical complex and pain signaling through dual stimulation sites.12

Treatment Protocol

  • Acute Treatment: 20-60 minutes at the onset of headache
  • Preventive Treatment: Not specified
  • Approved Age: ≥18 years
  • Location: Forehead and occiput (back of head)

Evidence Summary

Acute Treatment:

In adult patients with episodic migraine, Relivion (1-hour stimulation within 30-60 minutes from headache onset) showed superiority over active sham for acute treatment. Two randomized controlled trials demonstrated benefits in modified intention-to-treat population:78,79

  • Pain freedom at 2 hours: OR 4.27 (95% CI 1.69-10.75)
  • Pain relief at 2 hours: OR 2.81 (95% CI 1.06-7.49)
  • Sustained pain freedom at 24 hours: OR 6.08 (95% CI 2.06-17.94)
  • Adverse events infrequent and usually mild, some early withdrawals due to not tolerating paresthesias
IHS Recommendation - Acute Treatment

Weak in favor (↑)
Quality of evidence: Very low (⊕⊝⊝⊝)

The panel conditionally recommends the use of Relivion for the treatment of acute migraine attacks in adult patients with episodic migraine.

Preventive Treatment:

No randomized controlled trial met the eligibility criteria for preventive treatment assessment.

IHS Recommendation - Prevention

No recommendation

No evidence-based recommendation available.

Expert Consensus Suggestions

  1. Relivion can be an option for the acute treatment of migraine in adults with chronic migraine80
  2. Relivion can be an option for preventive treatment of adult patients with episodic migraine81,82

Practical Considerations

  • Advantages: Dual stimulation site may provide comprehensive coverage, flexible treatment duration (20-60 minutes)
  • Limitations: Currently not covered by insurance, high unit cost, device accessibility outside the US
  • Safety: Some patients may not tolerate paresthesias arising from stimulation

tVNS (Transauricular Vagus Nerve Stimulation)

tVNS Device

Mechanism of Action

tVNS delivers transauricular vagus nerve stimulation through the ear. The device works by modulating brainstem nuclei and functional connectivity in the vagal nerve pathway.13-15

Treatment Protocol

  • Acute Treatment: Not specified
  • Preventive Treatment: 4 hours per day
  • Approved Age: ≥3 years (CE-marked only)
  • Location: Cymba conchae (part of outer ear)

Evidence Summary

Acute Treatment:

No randomized controlled trial met the eligibility criteria for acute treatment assessment.

IHS Recommendation - Acute Treatment

No recommendation

No evidence-based recommendation available.

Preventive Treatment:

In adult patients with chronic migraine, tVNS (4 hours daily) was not superior to active sham for preventive treatment. One randomized controlled trial failed to meet the primary endpoint (monthly migraine days reduction: MD −2.6, 95% CI −5.58 to 0.38) in intention-to-treat population.83

  • No change in monthly acute medication use days: MD −0.7 (95% CI −1.79 to 3.19)
  • No change in MIDAS score: MD −3.1 (95% CI −27.9 to 21.7)
  • Change in HIT-6 score: MD 1.3 (95% CI 2.26-4.86)
  • Active sham led to a significant reduction in monthly headache days compared to active intervention
IHS Recommendation - Prevention

No recommendation
Quality of evidence: Very low (⊕⊝⊝⊝)

There were no solid efficacy data to recommend the use of tVNS for preventive migraine treatment.

Expert Consensus Suggestion

  1. Transauricular vagus nerve stimulation in general (not limited to the exact tVNS device) may have a role in migraine prevention13,84,85

Practical Considerations

  • Advantages: Available over-the-counter in Europe, CE-marked, can be used in children as young as 3 years
  • Limitations: Long daily treatment duration (4 hours), limited efficacy data, optimal stimulation parameters remain to be studied
  • Safety: Generally well tolerated, though active sham showed unexpected effects

Ozilia

Ozilia Device

Mechanism of Action

Ozilia delivers intranasal kinetic oscillation stimulation. The device works by modulating parasympathetic outflow and upregulating intrinsic functional activity in the limbic system.16

Treatment Protocol

  • Acute Treatment: Not specified
  • Preventive Treatment: 10 minutes each nostril once per week (chronic migraine only)
  • Approved Age: ≥18 years (CE-marked only)
  • Location: Intranasal (each nostril)

Evidence Summary

Acute Treatment:

In patients with episodic migraine, Ozilia (15 minutes each nostril) showed marginal superiority over inactive sham for acute treatment. A single randomized controlled trial demonstrated benefits in per-protocol population:86

  • Pain freedom at 2 hours: OR 11.00 (95% CI 1.16-103.9)
  • Sustained pain freedom at 24 hours: OR 8.80 (95% CI 0.93-83.4)
  • Primary endpoint was change in pain intensity 15 minutes after stimulation completion (45 minutes from onset)
  • One patient experienced a vasovagal reaction
IHS Recommendation - Acute Treatment

No recommendation
Quality of evidence: Very low (⊕⊝⊝⊝)

There were no solid data to recommend Ozilia for the treatment of acute migraine attacks.

Preventive Treatment:

In patients with migraine, Ozilia (15 minutes each nostril daily) was not superior to inactive sham for preventive treatment. A single unpublished randomized controlled trial (NCT02243865) investigated preventive efficacy:87

  • Monthly migraine days reduction: MD 0.2 (95% CI −1.27 to 1.67, non-significant)
  • Paresthesia and nasolacrimal secretion were common
  • No serious adverse events reported
IHS Recommendation - Prevention

No recommendation
Quality of evidence: Very low (⊕⊝⊝⊝)

There were no solid data to recommend Ozilia for preventive migraine treatment.

Expert Consensus Suggestion

  1. Ozilia can be an option for preventive migraine treatment in adults with chronic migraine22

Practical Considerations

  • Advantages: Novel mechanism targeting intranasal pathways, CE-marked for chronic migraine prevention
  • Limitations: Requires inserting catheter into nostril and attaching to pump, feasibility concerns particularly for acute treatment, not covered by insurance, high cost
  • Safety: Paresthesia and nasolacrimal secretion common, rare vasovagal reactions

Summary of Recommendations

The following table provides a comprehensive summary of evidence-based recommendations and expert consensus suggestions for all FDA-cleared and CE-marked non-invasive neuromodulation devices:

Device Acute Treatment Recommendation Preventive Treatment Recommendation Key Expert Consensus Suggestions
SAVI Dual Weak in favor (↑)
Quality: Low
For EM with aura		 No recommendation
No eligible RCTs		 • Acute treatment in EM/CM with/without aura31
• Prevention in adults, adolescents, and pregnant patients31-36
Cefaly Weak in favor (↑)
Quality: Moderate
For EM with/without aura		 Weak in favor (↑)
Quality: Very low
For EM		 • Acute treatment of pediatric and vestibular migraine39,40
• Acute treatment in CM41
• Prevention in CM and MOH, pediatric and adult43-48
gammaCore Sapphire No recommendation
Quality: Low
Primary endpoint not met		 Weak in favor (↑)
Quality: Moderate
For EM/CM		 • Acute treatment of vestibular migraine49-52
• Acute treatment in adolescents53
• Acute treatment in CM and MOH54-57
• Prevention of menstrual migraine61
• Prevention in CM60
HeadaTerm No recommendation
No eligible outcomes		 No recommendation
No eligible RCTs		 • Acute treatment in EM62
• Prevention based on predicate device equivalence to Cefaly
Nerivio Weak in favor (↑)
Quality: Very low
For EM		 Weak in favor (↑)
Quality: Very low
For EM/CM		 • Acute treatment in pregnant women and menstrual migraine65,66
• Acute treatment in pediatric patients ≥8 years67-70
• Acute treatment in CM71,72
• Management of MOH73,74
• Combined with behavioral intervention75
• Prevention in adolescents77
Relivion Weak in favor (↑)
Quality: Very low
For EM		 No recommendation
No eligible RCTs		 • Acute treatment in adults with CM80
• Prevention in adults with EM81,82
tVNS No recommendation
No eligible RCTs		 No recommendation
Quality: Very low
Primary endpoint not met		 • Transauricular VNS in general may have a role in migraine prevention13,84,85
Ozilia No recommendation
Quality: Very low
Marginal superiority		 No recommendation
Quality: Very low
No efficacy shown		 • Prevention in adults with CM22

Key Abbreviations

EM: Episodic migraine | CM: Chronic migraine | MOH: Medication overuse headache

Safety, Tolerability, and Future Directions

Safety Profile

Non-invasive neuromodulation devices generally demonstrate excellent safety profiles with minimal adverse events. Most reported adverse events across studies were mild and transient, including:

  • Skin irritation or redness at application sites (particularly with electrical stimulation devices)
  • Paresthesias or tingling sensations during stimulation
  • Mild discomfort during device application
  • Rare cases of vasovagal reactions (with intranasal devices)

Serious adverse events were rare across all device types. Importantly, these devices do not interact with medications, carry no risk of medication overuse/adaptation headache, and can be safely discontinued without withdrawal effects.

Challenges in Device Research

Evaluating non-invasive neuromodulation devices presents unique methodological challenges that affect evidence quality. Device trials face inherent constraints including difficulty implementing reliable sham controls, recruiting adequate sample sizes, and operating under different financial and resource constraints than pharmaceutical companies.

Key Methodological Limitations

Most reviewed randomized controlled trials were initiated before the publication of the International Headache Society's 2021 neuromodulation device controlled trial guidelines, resulting in methodological approaches not aligned with current standards. Primary limitations included imprecision due to small sample sizes, various risk-of-bias concerns, and inconsistent outcome measures across studies.18

Sham Control Challenges

Implementing proper sham controls needed a fundamental methodological challenge in device trials. While an optimal sham device should replicate the active intervention's sensory characteristics without delivering therapeutic effects, emerging evidence suggests this ideal is difficult to achieve in practice.

Recent research has revealed that presumed non-therapeutic sham gammaCore can unexpectedly modulate the trigeminal-autonomic reflex, challenging its validity as a true sham. This phenomenon extends to transauricular vagus nerve stimulation studies, where sham stimulation (1 Hz) unexpectedly outperformed active stimulation (25 Hz), with both frequencies affecting functional connectivity in the vagal nerve pathway.83,90

Access and Cost Considerations

Expanded insurance coverage would enhance cost-effectiveness and device accessibility. Data shows increased device utilization in systems with better coverage, such as the Veterans Administration Health Care System and certain commercial insurers. Removing cost barriers would likely yield reduced healthcare utilization and improved workplace productivity.93-95

International Headache Society Position

The International Headache Society positions neuromodulation devices as valuable components in the migraine treatment landscape, especially for patients who prefer non-drug therapies, respond inadequately to medications, experience adverse effects, or have contraindications to pharmacological treatments. The Society supports using various FDA-cleared or CE-marked neuromodulation technologies, recognizing their therapeutic efficacies and advantages in terms of minimal side effects, lack of systemic interactions, and no risk of medication overuse headache.92

Conclusion

Non-invasive neuromodulation devices offer innovative alternatives for migraine management, providing valuable options for patients seeking non-pharmacological treatments. While current evidence quality varies from very low to moderate, these devices demonstrate promising efficacy for both acute and preventive migraine treatment with excellent safety profiles.

The International Headache Society panel issued weak (conditional) recommendations in favor of several devices for both acute treatment (SAVI Dual, Cefaly, Relivion, and Nerivio) and preventive treatment (gammaCore Sapphire, Cefaly, and Nerivio). No evidence-based recommendations could be made for HeadaTerm (both indications), tVNS (both indications), Ozilia (both indications), gammaCore Sapphire (acute), SAVI Dual (prevention), and Relivion (prevention) due to insufficient eligible randomized controlled trial data.

Additional expert consensus suggestions extend potential applications to specific patient populations including pediatric patients, pregnant women, and those with chronic migraine, vestibular migraine, menstrual migraine, and medication overuse/adaptation headache. These suggestions provide valuable guidance when formal evidence-based recommendations are not available.

Most existing devices received weak recommendations due to limitations in study quality and precision, as well as considerations regarding device accessibility and insurance coverage. Despite varying levels of evidence-based recommendations, these devices may be integrated into clinical practice based on individual patient needs, preferences, and circumstances.

Important Clinical Disclaimer

This information is based on International Headache Society evidence-based guidelines and expert consensus recommendations. It should not replace professional medical advice, diagnosis, or treatment. Healthcare providers should consider individual patient circumstances, preferences, and contraindications when recommending non-invasive neuromodulation devices. Some recommendations in these guidelines may not fully align with current FDA-cleared indications for specific devices. Clinicians should exercise sound medical judgment in applying both regulatory guidance and professional society recommendations.

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