Migraine treatment with external concurrent occipital and trigeminal neurostimulation-A randomized controlled trial.

OBJECTIVE: To evaluate the efficacy and safety of concurrent non-invasive stimulation of occipital and trigeminal nerves in acute treatment of migraine with or without aura. BACKGROUND: Non-invasive neuromodulation devices stimulating a single peripheral nerve or anatomic distribution are routinely used by patients with migraine refractory to the first-line drugs or those who opt out of pharmaceutical treatment. Concurrent occipital and trigeminal stimulation was described in an invasive setting, and its safety cost outweighed its efficacy gain. This study evaluated the efficacy and safety of an external concurrent occipital and trigeminal device in acute treatment of migraine. DESIGN AND METHODS: This was a randomized, sham-controlled, double-blind, multi-center trial. Patients 18 years of age or older who met the International Classification of Headache Disorders (2018) diagnostic criteria for migraine with or without aura, reported 1-6 migraine attacks per month, and other headaches no more than 6 days per month were enrolled. Of 131 intention-to-treat participants (67 and 64 in the active and sham groups, respectively), 109 (50 and 59 in the active and sham groups, respectively) treated at least one migraine episode. Reduction of migraine headache (pain relief) 2 h after treatment initiation was the primary efficacy endpoint. Pain relief at 1 h, and pain freedom and relief in most bothersome symptom at 2 h after treatment initiation were the secondary endpoints. Freedom from most bothersome symptom at 2 h and sustained pain freedom 24 h after treatment initiation were among the exploratory endpoints. RESULTS: Sixty percent of participants (30/50) in the active arm reported pain relief at 2 h after initiation of the first eligible treatment (primary outcome) compared to 37% (22/59) in the control arm (difference, 23%; 95% confidence interval [CI], 2%-41%; p = 0.018). Pain freedom at 2 h without rescue medication was reported by 46% (23/50) of participants in the active arm and by 12% (7/59) of participants in the sham arm (p < 0.001). Pain freedom 2 h after the treatment and, subsequently, at 24 h, was reported by 4.25 times more participants in the active arm (36%; 18/50) than in the sham arm (8%; 5/59). The 28% difference was statistically significant (95% CI, 1%-43%; p < 0.001). A 4.25-fold difference was also observed comparing the proportion of participants free from pain and most bothersome symptom 2 h after the stimulation (47% [17/36] and 11% [5/45] in the active and sham arms, respectively; 95% CI, 14%-54%; p < 0.001). Adverse events were not serious or severe. All study-related events resolved without treatment. CONCLUSION: External concurrent occipital and trigeminal neurostimulation is a well-tolerated, safe, and effective migraine treatment that provided a fast and durable relief and freedom from migraine pain and associated symptoms in a randomized setting. The observed safety and performance suggest external concurrent occipital and trigeminal neurostimulation is a viable alternative to the currently available acute migraine treatments. TRIAL REGISTRATION: clinicaltrials.gov identifier NCT03631550.

External Concurrent Occipital and Trigeminal Neurostimulation Relieves Migraine Headache: A Prospective, Randomized, Double-Blind, Sham-Controlled Trial.

INTRODUCTION: Current external peripheral nerve stimulation devices stimulate only one nerve. This prospective, randomized, double-blind, sham-controlled trial assessed efficacy, safety, and tolerability of a novel external combined occipital and trigeminal neurostimulation (eCOT-NS) device as a self-administered home treatment for migraine (Relivion®MG, Neurolief Ltd; Netanya, Israel). METHODS: Episodic and chronic migraine subjects (N = 55) were randomized to receive active (n = 27) or sham (n = 28) treatment. Subjects received eCOT-NS devices and performed 60 ± 20-min home treatments within 45 min of migraine episode onset. The primary endpoint was relative (percent) change in mean baseline VAS pain scores 1 h after treatment initiation. Treatment outcomes assessed at 1-, 2-, and 24-h post-treatment initiation were pain reduction and proportion of pain-free subjects and treatment responders, defined as ≥ 50% pain reduction. Categorical pain ratings (none, mild, moderate, and severe pain) were also analyzed. RESULTS: Active stimulation was significantly more effective than sham stimulation for decreasing pain intensity at 1 h (53% vs. 10%), 2 h (52% vs. 17%), and 24 h (71% vs. 34%). Pain-free ratings were greater for the active treatment arm at 1 h (29.2% vs. 16%), 2 h (41.7% vs. 20%), and 24 h (65.2% vs. 40%). The number of subjects with baseline moderate or severe migraine pain who were pain-free at 2 h was significantly greater among active treatment subjects (43% vs. 10.5%). The responder rate was significantly higher among the active treatment group at 1 h (67% vs. 20%), 2 h (66.7% vs. 32%,), and 24 h (78.3% vs. 48%). Overall headache relief was significantly higher in the active treatment group at 1 h (67% vs. 26%) and 2 h (76% vs. 31.6%). Mild adverse events, reported by a minority of subjects, resolved spontaneously. CONCLUSIONS: eCOT-NS provides superior clinically meaningful relief and freedom from migraine pain, offering an effective and safe therapy for acute treatment of migraine. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT03398668.

As current external nerve stimulation devices stimulate only one nerve, this study assessed the effectiveness, safety, and tolerability of a new external nerve stimulation device that stimulates two nerves (occipital and trigeminal) as a self-administered home treatment for migraine (Relivion^®MG, Neurolief Ltd; Netanya, Israel). Fifty-five subjects with episodic and chronic migraine were randomly assigned to active (n = 27) or sham (dummy) treatment (n = 28). Subjects performed a 60-min home treatment within 45 min of migraine onset. The primary endpoint was the change in pain intensity 1 h after treatment initiation. Active treatment was significantly more effective than sham stimulation for decreasing pain intensity at 1 h (53% vs. 10%) and 2 h (52% vs. 17%). Pain-free ratings were also greater for the active treatment arm at 1 h (29.2% vs. 16%) and 2 h (41.7% vs. 20%). Overall headache relief was significantly higher in the active treatment group at 1 h (67% vs. 26%) and 2 h (66.7% vs. 32%). Mild, transient side effects reported by a few subjects resolved without treatment. This new external concurrent occipital and trigeminal neurostimulation (eCOT-NS) device provides superior and meaningful relief and freedom from migraine pain compared to sham treatment.

A device review of Relivion®: an external combined occipital and trigeminal neurostimulation (eCOT-NS) system for self-administered treatment of migraine and major depressive disorder.

Introduction: Many patients with migraine are non-responsive or intolerant to pharmaceutical or surgical interventions. Peripheral nerve stimulation (PNS) offers a potential solution for these patients. This review discusses the external combined occipital and trigeminal neurostimulation (eCOT-NS) provided by the Relivion®, a multi-channel head-mounted device for self-administered PNS.Areas covered: Challenges and advantages of PNS systems for the treatment of migraine and depression are introduced, followed by an overall review of clinical evidence of the efficacy of the Relivion® system in treating migraine. The supporting smartphone app and cloud-based analytics which enable remote treatment management by the health care provider are also discussed. Recent empirical indications for the potency of this PNS combination for the treatment of depression are also summarized.Expert opinion: Relivion® is an eCOT-NS system, featuring Food and Drug Administration-approved, noninvasive, self-administered, customizable, multi-focal PNS for the treatment of migraine. In accordance with current telehealth trends, the Relivion® also enhances remote disease management and personalization using digital-monitoring, cloud-based technology, and artificial intelligence. As research on this system progresses, it may become the preferred treatment for the management of a number of neurological and psychiatric diseases, with migraine and major depressive disorders as precedents.

Diagnosis and management of migraine in ten steps.

Migraine is a disabling primary headache disorder that directly affects more than one billion people worldwide. Despite its widespread prevalence, migraine remains under-diagnosed and under-treated. To support clinical decision-making, we convened a European panel of experts to develop a ten-step approach to the diagnosis and management of migraine. Each step was established by expert consensus and supported by a review of current literature, and the Consensus Statement is endorsed by the European Headache Federation and the European Academy of Neurology. In this Consensus Statement, we introduce typical clinical features, diagnostic criteria and differential diagnoses of migraine. We then emphasize the value of patient centricity and patient education to ensure treatment adherence and satisfaction with care provision. Further, we outline best practices for acute and preventive treatment of migraine in various patient populations, including adults, children and adolescents, pregnant and breastfeeding women, and older people. In addition, we provide recommendations for evaluating treatment response and managing treatment failure. Lastly, we discuss the management of complications and comorbidities as well as the importance of planning long-term follow-up.

Nutraceuticals in Acute and Prophylactic Treatment of Migraine.

OPINION STATEMENT: People who suffer from headaches often prefer nutraceutical treatment over traditional pharmacological approaches, due to fear of possible side effects, drug dependence, or addiction. Since treatment with nutraceuticals does not require a doctor's prescription, many patients rely on their own judgment as to when and which one to take, often without consultation or guidance from their physician. Some physicians could provide information about potential efficacy and side effects of various products, but many are not familiar with the nutraceuticals. Widespread skepticism persists among doctors about the effectiveness of these treatments. This is largely due to the lack of rigorous clinical studies. However, even when incontrovertible scientific evidence exists, many physicians remain distrustful of the evidence. The following review summarizes randomized controlled trials of some of the most commonly used non-pharmacological treatments, including magnesium, coenzyme Q10, riboflavin (vitamin B2), petasites, and feverfew (Table 1).