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Learn more: PMC Disclaimer | PMC Copyright Notice Adv Ther . 2026 Feb 16;43(4):1622–1638. doi: 10.1007/s12325-026-03500-y Search in PMC Search in PubMed View in NLM Catalog Add to search Practice-Based Consensus Amongst Indian Neurologists: Adopting Remote Electrical Neuromodulation for Effective Management of Migraine Debashish Chowdhury Debashish Chowdhury 1 Department of Neurology, GIPMER, New Delhi, India Find articles by Debashish Chowdhury 1 , Jaydip Ray Chaudhuri Jaydip Ray Chaudhuri 2 Department of Neurology, Yashoda Hospital, Hyderabad, India Find articles by Jaydip Ray Chaudhuri 2 , Pravar Passi Pravar Passi 3 Department of Neurosciences, CHL 114 Hospital, Indore, India Find articles by Pravar Passi 3 , Rajasekar Reddi Rajasekar Reddi 4 Department of Neurosciences, Max Institute of Neurosciences Saket, New Delhi, India Find articles by Rajasekar Reddi 4 , Rajiv Anand Rajiv Anand 5 Department of Neurology, BLK Super Specialty Hospital, New Delhi, India Find articles by Rajiv Anand 5 , Sumit Singh Sumit Singh 6 Department of Neurology, Artemis Agrim Institute of Neurosciences, New Delhi, India Find articles by Sumit Singh 6 , T K Banerjee T K Banerjee 7 Department of Neurology, National Neurosciences Centre, Kolkata, India Find articles by T K Banerjee 7 , Vikram Sharma Vikram Sharma 8 Department of Neurology, CARE Hospital, Hyderabad, India Find articles by Vikram Sharma 8 , Mayank Ravindra Dhore Mayank Ravindra Dhore 9 Department of Medical Affairs, Dr. Reddy’s Laboratories, Mumbai, India 10 Department of Medical Affairs, Dr. Reddy’s Laboratories, Ltd, Hyderabad, 500034 India Find articles by Mayank Ravindra Dhore 9, 10, ✉ , Sujeet Narayan Charugulla Sujeet Narayan Charugulla 10 Department of Medical Affairs, Dr. Reddy’s Laboratories, Ltd, Hyderabad, 500034 India Find articles by Sujeet Narayan Charugulla 10 , Bhavesh P Kotak Bhavesh P Kotak 10 Department of Medical Affairs, Dr. Reddy’s Laboratories, Ltd, Hyderabad, 500034 India Find articles by Bhavesh P Kotak 10 , Sukhpreet Singh Sukhpreet Singh 11 Department of Strategic Marketing, Dr. Reddy’s Laboratories, Hyderabad, India Find articles by Sukhpreet Singh 11 Author information Article notes Copyright and License information 1 Department of Neurology, GIPMER, New Delhi, India 2 Department of Neurology, Yashoda Hospital, Hyderabad, India 3 Department of Neurosciences, CHL 114 Hospital, Indore, India 4 Department of Neurosciences, Max Institute of Neurosciences Saket, New Delhi, India 5 Department of Neurology, BLK Super Specialty Hospital, New Delhi, India 6 Department of Neurology, Artemis Agrim Institute of Neurosciences, New Delhi, India 7 Department of Neurology, National Neurosciences Centre, Kolkata, India 8 Department of Neurology, CARE Hospital, Hyderabad, India 9 Department of Medical Affairs, Dr. Reddy’s Laboratories, Mumbai, India 10 Department of Medical Affairs, Dr. Reddy’s Laboratories, Ltd, Hyderabad, 500034 India 11 Department of Strategic Marketing, Dr. Reddy’s Laboratories, Hyderabad, India ✉ Corresponding author. Received 2025 Jul 14; Accepted 2025 Sep 4; Issue date 2026. © The Author(s) 2026 Open Access This article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, which permits any non-commercial use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc/4.0/ . PMC Copyright notice PMCID: PMC13065551 PMID: 41697517 Abstract Introduction Migraine is a major cause of disability in India, disproportionately affecting women and adolescents. Although traditional pharmacological treatments exist, side effects and poor adherence have increased interest in non-pharmacological options such as remote electrical neuromodulation (REN). However, clinical adoption of REN remains limited because of the absence of clear, India-specific guidelines. Methods An Indian consensus was developed through a two-phase Delphi process involving 49 neurologists. Phase 1 included a scientific committee of eight neurologists who conducted a targeted literature review on REN and formulated 27 consensus statements. In phase 2, 41 neurologists from across India participated in modified Delphi rounds to finalize these statements. Results Statements achieving over 60% agreement identified REN as a promising and well-tolerated non-pharmacological therapy that addresses limitations of current migraine treatments. High consensus (75–97.22%) highlighted REN’s favorable safety profile, minimal adverse events, and suitability for adolescents and women of childbearing age. Conclusion This Indian consensus provides practical guidance for integrating REN into migraine management. The REN device shows potential as a first-line or adjunct therapy, particularly for patients facing challenges with pharmacological treatment adherence, supporting its wider adoption in clinical practice. Supplementary Information The online version contains supplementary material available at 10.1007/s12325-026-03500-y. Keywords: Delphi consensus, Medication overuse headaches, Migraine, NSAIDs, Remote electrical neuromodulation, REN Key Summary Points Why carry out this study? Migraine causes significant disability in India, especially among women and adolescents, with current pharmacological treatments limited by side effects and poor adherence, highlighting an unmet need for effective non-pharmacological options. This study aimed to develop a consensus among Indian neurologists on the clinical use and integration of remote electrical neuromodulation (REN) as a treatment option for migraine. What was learned from the study? The consensus showed that REN is a promising, well-tolerated non-pharmacological option preferred for its safety profile, minimal adverse effects, and suitability for diverse patient groups, including adolescents and women of childbearing age. Although REN is not yet supported by level A comparative evidence, expert opinion, and early clinical experience suggest REN could be a valuable adjunct or alternative in personalized migraine management. This highlights the need for increased awareness and further rigorous studies to better define its role in clinical practice. Open in a new tab Introduction The World Health Organization’s Intersectoral Global Action Plan on Epilepsy and Other Neurological Disorders ranks headache disorders as the second most burdensome neurological disease after stroke and the leading cause in young and midlife adults, underscoring the need for equitable access to care and policy prioritization [ 1 ]. Achieving Sustainable Development Goal 3 by 2030 will require integrating headache care into broader health strategies through prevention, reduced medication overuse, improved access in low- and middle-income countries, and multidisciplinary management to reduce disability and enhance productivity [ 2 ]. Primary headache burden varies by age, comorbidities, and medication use, offering key data to refine Global Burden of Disease disability weights [ 3 ]. Migraine, a primary headache disorder marked by recurrent, often life-long attacks of throbbing unilateral pain aggravated by activity and accompanied by photophobia, phonophobia, nausea, vomiting, and cutaneous allodynia, affects around 15.2% of the global population and is the leading cause of years lived with disability in women [ 4 ]. Presentation varies in frequency, aura status, comorbidities, and treatment response, underscoring the need for individualized care [ 4 ]. Diagnosis relies on monthly migraine days and monthly headache days [ 5 ]. Globally, migraine ranks third among neurological disorders in disability-adjusted life years (DALYs), after stroke and neonatal encephalopathy, contributing 16% of neurological DALYs compared with 1.6% for tension-type headache [ 6 ]. On any given day, 15.8% of the population has a headache, and 7.0% of these are migraine [ 7 ]. It is the top cause of DALYs in individuals aged 5–19 years and second in those aged 20–59 years [ 6 , 8 ]. In India, the Global Burden of Disease Study (2019) identified headache disorders as the most prevalent neurological condition, affecting 488 million people, with migraine alone accounting for 213.9 million cases, predominantly in women [ 9 ]. Prevalence estimates are 11.6% in men and 21.0% in women globally [ 7 , 10 ], and 7.9% in male individuals vs. 25.3% in female individuals in one Indian study [ 11 ]. Migraine management combines acute and preventive therapies. Acute therapies such as triptans, ergotamine derivatives, ditans, gepants, non-steroidal anti-inflammatory drugs (NSAIDs), and neuromodulation devices are chosen on the basis of attack severity and patient profile. Ergot derivatives are reserved for cases unresponsive to safer options because of their tolerability and cardiovascular risks [ 12 ]. Preventive treatments include anticonvulsants, beta-blockers, angiotensin receptor blockers, triptans, calcitonin gene-related peptide (CGRP) monoclonal antibodies, and neuromodulation devices [ 13 ]. The American Academy of Neurology recommends triptans as first-line therapy for moderate-to-severe attacks, and the American Headache Society consensus statement advises trial of at least two oral triptans before switching medications [ 14 ]. Despite pharmacological advances, challenges such as poor adherence, side effects, high treatment costs, medication overuse headache (MOH), and progression to chronic migraine remain. Preventive treatment adherence is as low as 20.4% [ 15 ]. Northern India reports probable MOH in 3.0% of adults, with a higher prevalence in women (4.3%) than men (0.7%) [ 16 ]. Gaps in current care have driven interest in non-pharmacological options such as non-invasive neuromodulation, including transcranial magnetic stimulation (TMS), non-invasive vagal nerve stimulation, and external trigeminal nerve stimulation [ 17 , 18 ]. The REN device targets peripheral nerves in the upper arm to activate conditioned pain modulation, a pathway often deficient in patients with migraine [ 19 ]. The device is worn for 45-min sessions, is non-invasive, pill-free, and injection-free, and stimulates nociceptive A-δ and C fibers to engage endogenous pain control mechanisms [ 20 ]. Repeated activation may strengthen pain modulation networks, potentially lowering attack frequency [ 21 ]. Nerivio® (Theranica, Dr. Reddy’s Laboratories, India) is currently the only REN device cleared for migraine treatment in the USA, parts of Europe, South Africa, and India, for acute and/or preventive treatment in patients aged ≥ 12 years [ 19 ]. Studies show REN is non-inferior to drugs for mild-to-moderate migraine and has limited, non-serious adverse effects [ 17 , 21 , 22 ]. The International Neuromodulation Society has published evidence-based guidelines on neuromodulation therapies [ 23 ]. While these guidelines provide general recommendations for safe and effective use, they do not specifically address the use of REN for migraine [ 23 ]. The REN device is the first US Food and Drug Administration (FDA)-approved and CE-marked drug-free wearable therapy for both acute and preventive migraine management and has recently been introduced in India [ 24 ]. Unlike TMS or non-invasive vagus nerve stimulation (nVNS), which are available only in select hospital settings and require specialized infrastructure, REN devices are portable, patient-operated, and can be used remotely without such requirements. Clinical studies have demonstrated their efficacy and tolerability in diverse patient groups, making REN a valuable non-pharmacological alternative [ 25 ]. Globally, the average per-treatment cost of REN has been reported to be lower than that of TMS or nVNS, yet higher than most oral pharmacological options, which may influence uptake [ 26 , 27 ]. Together with the unmet needs of patients intolerant or unresponsive to drugs, these considerations highlight the importance of developing an Indian practice-based consensus on the use of neuromodulation devices. Methods A panel of 49 neurologists was selected on the basis of predefined criteria to ensure clinical expertise, geographic diversity, and practical experience with migraine management in India. Each panelist had at least 5 years of clinical experience, familiarity with non-pharmacological and neuromodulation treatments, and active involvement in patient care or academic work. The experts were selected for their substantial experience in migraine management and familiarity with neuromodulation techniques, with a primary focus on the REN device. While a subset of experts have experience with other neuromodulation modalities, such as TMS and nVNS, most panelists were directly involved in the clinical use or prescribing of REN in India. All members demonstrated at least a working knowledge of REN’s mechanism, indications, and clinical evidence, with some participating primarily on the basis of a scoping literature review. This composition was designed to combine practical clinical insights with up-to-date scientific evidence. All panelists provided informed consent before participation in the Delphi process. The consensus was conducted in two phases. In phase 1, a national scientific committee of eight neurologists was formed that conducted a targeted scoping literature review to identify relevant resources across several electronic databases, including PubMed/MEDLINE, Embase, CINAHL, Web of Science, Scopus, and Google Scholar. These sources were chosen to ensure wide coverage of biomedical, nursing/allied health, and multidisciplinary evidence. No clinical trial registries were searched, as the focus was on peer-reviewed published evidence that could directly inform clinical practice in the Indian context. The objective of the review was not to perform an exhaustive systematic synthesis, but rather to map the breadth of current literature, highlight key studies, and provide an evidence-informed foundation for the Delphi discussions. A scoping rather than systematic approach was deliberately adopted, as the intent was to capture representative, high-relevance publications and synthesize them with clinical expertise rather than to quantitatively pool outcomes. This ensured that the consensus process remained evidence-informed yet practice-oriented. The title/abstract keyword used in the database search was “remote electrical neuromodulation.” The literature search for developing the consensus statements was conducted from January 2000 to May 2024. The medical subject heading (MeSH) terms used for the search were “remote electrical neuromodulation,” “migraine,” “migraine without aura,” “migraine with aura,” “acute migraine management,” “non-pharmacological treatment,” “headache,” “neuromodulation,” and “electrical stimulation.” Additionally, supplementary searches to capture additional relevant literature using other keywords such as “transcutaneous electrical nerve stimulation,” “non-invasive neuromodulation,” “migraine prophylaxis,” “REN,” and “consensus” were also conducted. In addition, a targeted search was conducted for pharmacological migraine management evidence (including triptans, ergot derivatives, and other acute therapies) in line with updated global and Indian recommendations. Recent high-quality guidelines, systematic reviews, and randomized controlled trials published within the last 5 years were prioritized. Levels of evidence (LoE) and recommendation grades were assigned using the Oxford Centre for Evidence-Based Medicine (OCEBM) criteria [ 28 ], and the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) [ 29 ] approach was applied to assess the quality of supporting evidence. A concise evidence summary table, including LoE and grades, was prepared and provided to all panelists before the first Delphi round. This ensured that their ratings and comments were informed by both current literature and their clinical experience. Inclusion Criteria The study included research focusing on adult participants (≥ 18 years) with a clinical diagnosis of migraine, including both episodic and chronic types. For this review, the term “Indian context” referred to studies conducted in India or involving Indian populations, as well as studies from other countries addressing healthcare infrastructure, clinical practices, cultural perceptions, or climatic/geographical factors relevant to migraine management in India. Priority was given to studies relevant to the Indian context or those providing insights that are applicable to the Indian cultural or geographical settings. Articles discussing REN as a primary or adjunctive drug-free management strategy for migraine were considered, including those that integrated lifestyle modifications and non-pharmacological approaches alongside REN. Eligible study types included peer-reviewed articles, systematic reviews, meta-analyses, randomized controlled trials (RCTs), cohort studies, and expert consensus documents with clearly defined methodologies and measurable outcomes such as improvements in migraine severity, frequency, or quality of life. Only studies published in English in the predefined year were included to ensure that the most recent and relevant advancements in REN were captured. Exclusion Criteria Articles addressing pharmacological interventions exclusively or focusing on invasive neuromodulation techniques, non-peer-reviewed articles, opinion pieces without supporting evidence, gray literature (defined as non-peer-reviewed or non-indexed sources such as conference abstracts without full-text availability, dissertations, government or industry reports not subjected to peer review, and other unpublished materials) were excluded. Studies with incomplete or unclear methodologies, such as studies lacking sufficient detail on study design, patient selection criteria, intervention protocols, or statistical analysis to permit assessment of validity, and outcomes, or conclusions, were precluded. Publications in languages other than English and studies published more than 10 years ago, unless foundational or seminal, were also excluded. Finally, duplicate studies, previously reviewed data, and articles with significant conflicts of interest or evident methodological biases were omitted to maintain the quality and integrity of the analysis. Two reviewers independently applied these criteria during screening, with disagreements resolved through discussion to minimize subjectivity. A flow diagram (Fig. 1 ) outlines the inclusion and exclusion criteria. Furthermore, a complete list of included studies for developing the consensus statements, along with bibliographic details, study design, population, and key outcomes, is provided in Supplementary Table S1 . Fig. 1. Open in a new tab Flowchart of inclusion and exclusion criteria. RCT randomized controlled trial, REN remote electrical neuromodulation Formulation of Consensus Statements Following this, the national scientific committee formulated 27 consensus statements through a questionnaire. The questionnaire focused on several key areas: (1) challenges in migraine management, including issues related to diagnosis, treatment adherence, and the side effects of existing therapies; (2) underutilization of prophylactic treatments with reasons and the potential role of REN as a preventive measure; (3) effectiveness and tolerability of REN by assessing its clinical usefulness in both acute and preventive migraine management; and (4) patient-specific considerations, which evaluated the role of REN in diverse patient populations, including those with comorbidities or contraindications to pharmacological treatments. LOE, OCEBM, and GRADE ratings for each statement were drawn directly from the targeted literature review described above, ensuring evidence-based alignment, and were made available to the panel during voting. The consensus-building process was carried out in phase 2. It involved an expert panel of 41 neurologists from different regions of India who participated in the modified Delphi process, which involved digital and in-person meetings. The eight national scientific committee members responsible for formulating the statements did not participate in the voting. The voting on the consensus statements was conducted in two rounds. To assess the level of agreement among panelists, we employed a structured modified Delphi process with predefined consensus thresholds. Given the emerging nature of REN in clinical migraine management and the evolving real-world experience with this modality in India, a three-tiered classification of consensus was adopted. Statements endorsed by > 70% of respondents were classified as reflecting high consensus, those with 51–70% agreement as moderate consensus, and those with < 50% agreement as low consensus or no consensus. This stratification aligns with prior Delphi studies in neurology and pain medicine, where a ≥ 70% threshold has commonly been used to indicate strong convergence of expert opinion, particularly in fields with limited large-scale comparative trial data. Importantly, this graded approach allows nuanced interpretation of findings, recognizing that even moderate agreement among experienced clinicians can offer valuable directional insights in underexplored therapeutic areas such as REN. The phase 1 literature review revealed that while several clinical studies (including RCTs and real-world evidence) support the safety and efficacy of the REN device for both acute and preventive migraine treatment, gaps remain in head-to-head comparative data, long-term outcomes, and usage in diverse subpopulations. These gaps, along with implementation-related questions, directly informed the structure and content of the phase 2 consensus statements. Discussions were held about statements that did not reach a consensus in the first round. The discussion focused on clarifying ambiguities, resolving areas of disagreement, and ensuring that the statements were pertinent to the Indian context. This led to either the reframing or elimination of statements. Following this, a second round of voting was held for the modified statements. Ethical Considerations Ethical clearance for the study was obtained from the Aditya College of Engineering and Advanced Studies (ACEAS) Independent Ethics Committee, Gujarat, India, approval number EC/BQ/P-1/3/3/25, dated 03 March 2025. The study was conducted in accordance with the Declaration of Helsinki (1964) and its later amendments. All participating experts provided written informed consent before their involvement in the consensus meetings. Confidentiality of participant responses was maintained throughout the study, and any potential conflicts of interest were fully disclosed. Results The results of the consensus were categorized on the basis of the level of agreement with the statements, considering the criteria for consensus attainment: low consensus (< 50% votes), moderate consensus (51–70% votes), and high consensus (> 70% votes). A total of 27 statements were presented. The results show that 14 statements achieved high agreement regarding using REN for migraine management, with 83.33% of clinicians recognizing its key role as a non-pharmacological treatment approach. Its targeted mechanism of action with minimal adverse events was supported by 83.33% of members, while 77.78% agreed that it has a lower risk of adverse events compared to pharmacological therapies. Furthermore, 97.22% of clinicians favored REN for women of childbearing age with family planning goals. Moderate consensus was achieved for 13 statements, with 51–70% agreement. This category included points such as the challenges of managing side effects such as weight gain, the factors influencing the choice of acute and preventive treatments, and the use of REN in patients with varied migraine frequency. Additionally, the barriers to initiating prophylactic treatment, such as the lack of awareness and concerns about adverse events, also had moderate consensus. Supplementary Table S2 provides detailed polling results for the various options discussed across different questions [ 21 , 24 , 30 – 52 ]. Discussion Preferred Acute and Preventive Migraine Treatment The management of migraine involves a combination of acute pharmacological therapies, preventive medications, and non-pharmacological approaches [ 53 ]. In recent years, neuromodulation devices have also been approved globally for the acute treatment of migraine [ 54 ]. Patient education is crucial, as migraine is a recurrent, episodic disorder without a definitive cure, but with appropriate treatment, the condition can be effectively controlled, enabling individuals to maintain a good quality of life. Delayed or inadequate treatment of migraine attacks not only reduces day-to-day functionality but also has socio-economic consequences and increases the likelihood of progression to chronic migraine [ 55 ]. For mild-to-moderate migraine attacks without significant gastrointestinal symptoms, oral NSAIDs (e.g., naproxen, ibuprofen, diclofenac) or acetaminophen, alone or in combination with caffeine, are recommended by both international and Indian guidelines [ 56 – 59 ]. These agents are cost-effective, widely available, and have a favorable safety profile compared to migraine-specific treatments. In cases where rapid relief is needed, parenteral NSAIDs such as 30 mg intravenous ketorolac or lysine acetylsalicylic acid are reasonable choices, supported by several global guidelines [ 11 , 60 ]. These are particularly valuable in emergency settings or in patients with severe pain onset where oral intake is impractical. For moderate-to-severe attacks from onset, or for mild-to-moderate attacks unresponsive to simple analgesics, migraine-specific agents such as triptans (e.g., sumatriptan, rizatriptan, zolmitriptan) are recommended. The recent international 2025 evidence-based guidelines for the pharmacological treatment of migraine [ 61 ] emphasize early administration in the headache phase to optimize pain relief, reduce recurrence, and improve functional outcomes. Triptans act as selective serotonin (5-HT 1 B/ 1 D) receptor agonists, promoting cranial vasoconstriction and inhibiting the release of pro-inflammatory neuropeptides, thereby addressing the underlying pathophysiology of migraine. While generally well-tolerated, they must be avoided in patients with coronary artery disease, cerebrovascular disease, uncontrolled hypertension, or other vasospastic disorders, as per both global and Indian recommendations. For patients with prolonged attacks or inadequate triptan response, ergot derivatives, particularly dihydroergotamine (DHE), remain an option. Dihydroergotamine continues to demonstrate clinical utility in refractory migraine cases [ 62 ] with multiple formulations (intranasal, intramuscular, and intravenous) available. However, their use is tempered by side effects, strict contraindications, and limited availability in some regions. Recent retrospective data suggest that repetitive intravenous DHE infusions can be administered cautiously even in patients with cardiovascular risk factors under strict monitoring [ 63 ]. Both triptans and ergots should be prescribed following a thorough cardiovascular risk assessment and in alignment with contemporary global and Indian guidelines [ 64 ]. Neuromodulation devices, including REN, are frequently employed as adjunctive treatments alongside pharmacological therapies, particularly in refractory migraine cases where patients have an inadequate response to conventional medications. Invasive or minimally invasive neuromodulation techniques, such as combined greater occipital nerve pulsed radiofrequency and botulinum toxin injections, have demonstrated marked reductions in pain intensity and headache days in small case series of refractory patients [ 65 ], supporting the therapeutic rationale for non-invasive, targeted approaches such as REN. The experts reached moderate consensus (52.63%) on NSAIDs being the preferred first-line acute therapy for patients experiencing ≥ 4 migraine days per month ( C1 ). NSAIDs are commonly chosen owing to their accessibility and effectiveness in alleviating pain. However, for combination therapy, NSAIDs + triptans (26.31%) were the preferred option. REN devices (15.78%), as a non-pharmacological adjunct, are also considered, although less frequently preferred than medication-based treatments. Beta-blockers were the most preferred option as the first-line preventive treatment for patients with no comorbidities and no prior preventive treatment (78.94%). According to a systematic review, beta-blockers (e.g., propranolol) effectively reduced the frequency of episodic migraine headaches, decreasing the number of attacks from five to three per month. While beta-blockers help reduce headaches by over 50%, patients may still experience a significant residual headache burden. Propranolol minimizes the need for analgesic medication and lessens the severity and duration of headaches [ 58 ]. Topiramate and amitriptyline were considered alternative treatments by the expert panel (10.52% each). Amitriptyline, a tricyclic antidepressant, has shown potential as a prophylactic treatment for migraine with careful titration over 6 months and has been identified as the optimal approach for prophylactic management [ 53 ]. Beta-blockers are the standard owing to their proven efficacy and safety profile in migraine prevention ( C2 ). Challenges in Managing Chronic Migraine This consensus highlighted several challenges and strategies related to migraine treatment in clinical practice. Weight gain was identified as the most challenging side effect to manage when prescribing preventive treatments for migraine, with 70% of experts agreeing on its significant impact ( C3 ). A recent review found that weight gain was the most common side effect associated with migraine medications [ 55 ]. Fatigue/somnolence and cognitive side effects were also noted but were considered less disruptive than weight gain. Discontinuation of oral prophylactic treatments within 6 months was reported by more than 25% of patients, mainly as a result of issues such as insufficient efficacy and side effects, emphasizing the need for improved patient engagement and personalized treatment plans ( C4 ). Treatment preference is a subjective evaluation that considers both the benefits of the treatment and its tolerability. In clinical trials of acute migraine treatments, preferences are hard to interpret because of differences in how patients weigh benefits and assess tolerability. Some patients prioritize treatment effectiveness, accepting mild and transient side effects. In contrast, others prefer treatments with a more favorable tolerability profile, even if they slightly reduce efficacy [ 30 ]. As per the experts, when considering acute treatments, factors such as route of administration, speed of onset, tolerability profile, and previous responses to acute medications were all found to strongly influence clinical decision-making, with these factors being interdependent ( C5 ). MOH is a common and potentially preventable secondary headache disorder caused by the excessive use of medications intended for primary headache management, especially migraine [ 58 ]. The lack of awareness of preventive treatments amongst patients who self-medicate was the most common reason for the overuse of acute medications, contributing to MOH. This underlines the need for better patient education ( C6 ). For pregnant or breastfeeding women, the preferred approach was non-pharmacological therapies such as REN (58.33%) along with medications with established safety profiles during pregnancy (36.11%) ( C7 ). Lastly, the cost-effectiveness of CGRP monoclonal antibodies was identified as the primary barrier to their use in preventive treatment, with 83.33% of experts citing this aspect as a significant limitation, followed by patient hesitancy toward injectable medications ( C8 ). Access to advanced migraine therapies such as CGRP monoclonal antibodies and gepants remains limited in India because of high costs, regulatory challenges, and restricted insurance coverage. Consequently, there is a pressing need for alternative non-pharmacological treatments such as REN to address these unmet clinical needs. Limited access to headache specialists, especially in low-resource settings, further exacerbates the treatment gap. The European Headache Federation and Lifting the Burden campaign recommend integrating community pharmacists into structured headache services to expand access, reduce system strain, and enable timely care [ 66 , 67 ]. Utilization of Prophylactic Treatment in Migraine Effective migraine management requires an accurate diagnosis before treatment initiation. Early intervention with effective medications is essential for controlling acute migraine attacks [ 53 ]. The experts (80%) concluded that more than 50% of patients were eligible for prophylactic therapies ( P1 ), indicating a high prevalence of individuals experiencing frequent migraine days each month. However, less than 50% of patients who experienced ≥ 4 migraine days per month and previously consulted non-neurologists were currently receiving prophylactic treatment, according to 61.11% of experts ( P2 ). This suggests a potential gap in access to specific preventive treatment, particularly among patients initially managed by non-neurologists. Developing guidelines for the prophylactic use of migraine medications and disseminating them through educational workshops for neurologists is essential in the Indian context [ 53 ]. The most significant barrier identified to initiating prophylactic treatment was the need for more awareness amongst patients and healthcare professionals about all the available options ( P3 ), with 66.67% of experts citing this as the primary reason for low adoption. Barriers such as concerns about side effects and a preference for acute treatment were noted less frequently. Notably, all experts reported always discussing the benefits of initiating or maintaining appropriate prophylactic therapy with patients experiencing ≥ 4 migraine days monthly ( P4 ), showing a strong commitment towards communicating the right preventive options. To improve prophylactic treatment uptake, 77.78% of experts agreed that better patient education and awareness programs would be the most effective strategy ( P5 ), emphasizing the importance of such initiatives, especially in the Indian context. Finally, the experts suggested that adherence rates might be slightly higher with REN devices than with pharmacological therapy ( P6 ), with 52.78% of experts favoring REN devices, which could provide a promising alternative for patients concerned with long-term medication use. REN Devices in Migraine Management REN is an effective, consistent, and safe option for acute migraine treatment in real-world settings, suitable as both a stand-alone alternative to medication and an adjunct to pharmaceutical treatments [ 46 ]. Need for REN in Migraine Management in India REN can be considered a viable alternative, especially in cases where patients may face adherence challenges with conventional therapies. A total of 79% of experts opined that the adherence rate for the current prophylactic therapies ranges from 25% to 50% at 6 months ( R1 ). Approximately 61.11% of experts identified side effects as the primary reason for patient reluctance toward prophylactic migraine treatments ( R2 ), even though fewer than 50% of patients reported limited effectiveness ( R3 ). Most experts estimated that 10–50% of patients experienced side effects ( R4 ), with weight gain reported by most experts as the most challenging to manage ( C3 ). Reflecting a growing preference for non-pharmacological options, 83% of experts observed that their patients expressed a notable interest in the REN device for migraine management ( R5 ). This highlights the important role of healthcare providers in patient education and shared decision-making regarding REN. In the Indian context, there is a cultural tendency among many patients to avoid or minimize the use of pharmacological treatments, driven by concerns over side effects, long-term medication dependence, and preferences for holistic or non-drug interventions. This reinforces the appeal of REN as a non-pharmacological therapy, making clinician-led education essential to optimize patient acceptance and adherence. Clinicians can improve treatment satisfaction and outcomes by integrating REN into individualized migraine management plans aligned with patient preferences. Exploring the Effectiveness and Tolerability of REN This consensus primarily focuses on the use of REN for migraine prevention in patients experiencing four or more attacks per month, consistent with prevailing guidelines. However, REN is also recognized as a promising non-pharmacological option for acute migraine treatment, either as a stand-alone therapy or in combination with pharmacological agents. This dual role is reflected in select consensus statements and discussion sections, highlighting expert opinions on the utility of REN across migraine management phases. The national scientific committee evaluated REN’s potential for migraine treatment and identified key factors such as its mechanism of action and safety profile as major strengths supporting its use. The ability of REN to target pain pathways without systemic side effects is widely regarded as its most compelling feature, with 83.33% of experts highlighting its non-invasive approach ( E1 ). REN’s safety profile is considered a major advantage (77% of experts), compared with pharmacological treatments, as it carries minimal risk of adverse events ( E2 ). Furthermore, REN is increasingly considered for use in patients at varied levels of migraine severity, with 80% of the panel agreeing that it can be offered for all migraine types—low, medium, and high frequency ( E3 ). The clinical evidence supporting REN for migraine treatment is persuasive. In a randomized trial, active REN stimulation resulted in 50% pain reduction within 2 h, compared to 26% with sham stimulation ( p < 0.02) [ 65 , 68 ]. A multicenter study found that 66.7% of participants using REN achieved pain relief, compared to 38.8% with sham ( p < 0.0001), and 37.4% were pain-free at 2 h ( p = 0.003) [ 51 ]. A chronic migraine study showed that 59.3% achieved pain relief at 2 h, with 64.4% sustaining it at 24 h ( p < 0.05) [ 67 , 69 ]. These findings confirm that REN offers a safe, effective, non-pharmacological alternative for migraine treatment, reduces reliance on medications, and improves patient outcomes. For adolescents (aged 12–18 years) who experienced ≥ 4 migraine days per month, where the parents were hesitant to begin pharmacological treatment, 75% of experts agreed that REN was successfully implemented as a stand-alone preventive therapy option in up to 30% of this vulnerable patient population ( E4 ). REN is also beneficial for adolescent patients with frequent episodic migraine, and factors that determine the choice of therapy, including limited regulatory-approved pharmacological drugs in this age group, comorbid conditions, compliance, parents, and patient preferences towards non-pharmacological interventions, influence the decision to prescribe REN ( E5 ). REN has shown promising results in migraine management, with multiple studies demonstrating benefits in pain relief, functional improvement, and safety across diverse patient populations [ 70 , 71 ]. Importantly, clinical guidelines recognize that neuromodulation devices, such as REN, are most commonly employed adjunctively alongside established pharmacological treatments, especially in refractory migraine cases, to enhance symptom control and tailor therapy to individual patient needs [ 72 ]. A pilot trial with 71 episodic migraine participants showed that REN provided significantly greater pain reduction than the control group [ 67 ]. A post hoc analysis of 99 adults revealed higher rates of 2-h pain relief (68.5%) and pain freedom (42.3%) in the REN group compared to usual care [ 65 ]. Additionally, an open-label extension study with 117 adults found that REN reduced the use of medications for acute migraine, suggesting complementary benefits to standard care [ 68 ]. Acute migraine treatments in special populations, including children and pregnant women, must be carefully tailored to address their specific healthcare needs and potential safety risks [ 73 ]. Overwhelmingly, 97% of the experts considered REN as a treatment option for this category, including women of childbearing age with episodic migraine who have family planning goals ( E6 ). A recent study evaluated the safety of REN for treating acute migraine in pregnant women. It compared 59 pregnant women who used REN for at least three treatments during their pregnancy to 81 in the control arm. The results showed no statistically significant differences in critical pregnancy outcomes, such as gestational age, baby’s birth weight, miscarriage rate, preterm birth rate, birth defects rate, stillbirth rate, and newborn meeting developmental milestones at 3 months postnatal between these two groups suggesting that REN is a safe, drug-free option for managing migraine during pregnancy [ 74 ]. The treatment response to REN therapy, according to 72% of the expert panel, can be assessed based on patient feedback, clinically meaningful improvements, and a minimum 50% reduction in migraine or headache days ( E7 ). As a result of its targeted approach, moderate agreement was reached by the experts that the REN device is to be preferred over other drug-free options, such as general relaxation techniques ( E8 ). Further, REN with the guided intervention of education and relaxation (GIER provided in REN app) demonstrated significantly higher rates of consistent pain relief (79.4% vs. 56.8%; p = 0.008), functional disability improvement (71.3% vs. 52.2%; p = 0.014), and return to normal function (37.5% vs. 17.5%; p = 0.005) compared to the REN-only group [ 73 ]. The side effects reported for REN are primarily local paresthesia or skin sensitivity at the device site, with no severe adverse events and a low incidence of device-related adverse events (1.96%). Despite these, users continued treatment, finding the benefits outweighing the discomfort [ 75 ]. In summary, REN is an effective, non-pharmacological treatment for migraine, providing significant pain relief and functional improvement. REN has shown positive outcomes in diverse patient populations—adults with acute and chronic migraine, adolescents, and women of childbearing age, including those with the intent of family planning and menstrual migraine [ 76 ], making it a valuable option for those seeking relief beyond traditional treatments. Limitations This consensus is subject to several limitations. While formal quantitative measures assessing stability between Delphi rounds were not performed as a result of study design constraints, this limitation has been acknowledged. Individual statements evolved throughout the process, reflecting ongoing discussions and the integration of new evidence. The diversity of expert opinions and the dynamic nature of the consensus process may have introduced some variation in the recommendations. Though findings from Indian settings are yet to be documented in published literature, the consensus reflects expert clinical opinion supported by global literature and early Indian experience. It is important to note that the majority of participating neurologists had substantial clinical experience with REN but may have limited hands-on experience with other neuromodulation devices. As a result, recommendations regarding other devices or therapies were based predominantly on literature review and international guidelines rather than direct patient management experience. Importantly, none of the currently available neuromodulation devices, including REN, have achieved level A evidence for migraine treatment. Therefore, these recommendations should be interpreted as preliminary practice-oriented guidance rather than definitive clinical directives. Despite these constraints, this first Indian consensus provides a strong foundation for further exploring REN’s role in migraine treatment, emphasizing the need for more comprehensive studies and broader inclusion of diverse patient populations in future research and guideline development. Given the expanding landscape of neuromodulation therapies for migraine, the expert panel opted to focus this consensus specifically on the REN modality delivered via the REN device. This decision was based on the relatively robust clinical evidence supporting REN devices’ safety and efficacy [ 25 ], as well as their US FDA clearance through the 510(k) pathway, which confirms that the device meets established safety standards and is substantially equivalent to legally marketed devices, while noting that this clearance does not constitute full US FDA approval of efficacy. Its growing use in real-world clinical practice further informed this focus. While other neuromodulation devices, such as TMS and VNS, also show promise, their inclusion was beyond the intended scope of this focused consensus. Future efforts may explore broader comparative evaluations as more data becomes available. Conclusions Migraine management continues to evolve with a focus on both acute and preventive treatments to reduce the frequency, severity, and impact of the attacks on individuals’ lives. The REN device’s safety profile, ease of use, and potential to reduce dependence on pharmacological therapies make it a valuable option in comprehensive migraine management. However, barriers such as patient education, awareness, and cost-effectiveness need to be addressed for more widespread adoption. As evidence supporting REN device effectiveness and safety rapidly evolves, it will become integral to overall migraine treatment strategies, offering clinicians and patients a formidable option in addition to existing therapies, ultimately achieving better outcomes for many more patients. Supplementary Information Below is the link to the electronic supplementary material. Supplementary file1 (PDF 263 KB) (263.2KB, pdf) Acknowledgements The authors like to acknowledge the generous support and participation of all the national expert panelists: Dr. J D Mukherjee, Dr. Amalan Mondal, Dr. Ashish Sharma, Dr. Sameer Arora, Dr. Manish Mahajan, Dr. Varun Rehani, Dr. Praveen Gupta, Dr. Atul Prasad, Dr. Jyothi Bala Sharma, Dr. Vivek Kumar, Dr. Sanjay Kumar Choudhary, Dr. Atul Agarwal, Dr. Mukul Varma, Dr. B K Gupta, Dr. Asad Abbas, Dr. J B Agadi, Dr. Ajit Verma, Dr. Avik Mukherjee, Dr. Pradeep Kumar, Dr. Abhinav Gupta, Dr. Venkatraman, Dr. Joy Desai, Dr. Praveen Chander, Dr. Kapil Singhal, Dr. Mayank Patel, Dr. Amit Vyas, Dr. Abhinav Raina, Dr. E Senthil Kumar, Dr. R Balakrishnan, Dr. Rajesh Shankar Iyer, Dr. Rutul Shah, Dr. Vikram Kishore Reddy, Dr. Abishek Gohel, Dr. Shiva Kumar R, Dr. P R Krishnan, Dr. Raghunandan Nadig, Dr. Prashant Makhija, Dr. Ashutosh Shetty, Dr. Rakesh Lalla, Dr. Arunkumar, Dr. Pankaj Singh. Medical Writing/Editorial Assistance Editorial assistance was provided by BioQuest Solutions Private Limited in the preparation of this article. This educational project was funded by Dr. Reddy’s Laboratories. We extend our sincere appreciation to Shweta I, Anuj R, Sathyakirubakaran S, and Azeem M. Author Contributions Conceptualization, Funding acquisition, Investigation, Methodology, Supervision, Validation, Writing–review & editing: Debashish Chowdhury, Jaydip Ray Chaudhuri, Pravar Passi, Rajasekar Reddi, Rajiv Anand, Sumit Singh, T K Banerjee, Vikram Sharma, Mayank Ravindra Dhore, Sujeet Narayan Charugulla, Bhavesh P Kotak, and Sukhpreet Singh. Project administration, resources, and software: Dr Reddy’s Laboratories, BioQuest Solutions Private Limited. Funding This study was supported by Dr Reddy’s Laboratories Ltd, India. The journal’s rapid service fees and open access were both funded by Dr Reddy’s Laboratories Ltd, India. Data Availability All data generated or analyzed during this study are included in this published article/supplementary information files. Declarations Conflict of Interest Nerivio ® is distributed by Dr. Reddy’s Laboratories in India. The expert committee, including Debashish Chowdhury, Jaydip Ray Chaudhuri, Pravar Passi, Rajasekar Reddi, Rajiv Anand, Sumit Singh, T K Banerjee, and Vikram Sharma, members of the scientific advisory board of Dr. Reddy’s Laboratories, declares that they have no competing interests. Mayank Ravindra Dhore, Sujeet Narayan Charugulla, Bhavesh P Kotak, and Sukhpreet Singh are employees of Dr. Reddy’s Laboratories. Ethical Approval Ethical clearance for the study was obtained from the Aditya College of Engineering and Advanced Studies (ACEAS) Independent Ethics Committee, Gujarat, India, approval number EC/BQ/P-1/3/3/25, dated 03 March 2025. The study was conducted in accordance with the Declaration of Helsinki (1964) and its later amendments. All participating experts provided written informed consent before their involvement in the consensus meetings. Confidentiality of participant responses was maintained throughout the study, and any potential conflicts of interest were fully disclosed. Digital informed consent was obtained from all the experts. Footnotes Publisher’s Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. References 1. Leonardi M, Martelletti P, Burstein R, et al. The World Health Organization intersectoral global action plan on epilepsy and other neurological disorders and the headache revolution: from headache burden to a global action plan for headache disorders. J Headache Pain. 2024;25:4. 10.1186/s10194-023-01700-3. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 2. Martelletti P, Leonardi M, Ashina M, et al. Rethinking headache as a global public health case model for reaching the SDG 3 health by 2030. J Headache Pain. 2023;24:140. 10.1186/s10194-023-01666-2. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 3. Waliszewska-Prosół M, Montisano DA, Antolak M, et al. The impact of primary headaches on disability outcomes: a literature review and meta-analysis to inform future iterations of the Global Burden of Disease study. J Headache Pain. 2024;25:27. 10.1186/s10194-024-01735-0. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 4. Raggi A, Leonardi M, Arruda M, et al. Hallmarks of primary headache: part 1 - migraine. J Headache Pain. 2024;25:189. 10.1186/s10194-024-01889-x. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 5. Migraine: The American Headache Society update on integrating new migraine treatments into clinical practice. 2021. Philadelphia: Lippincott Nursing Center; 2023. https://www.nursingcenter.com/getattachment/Clinical-Resources/Guideline-Summaries/Migraine/GuidelineSummary_Migraine_May-2023.pdf.aspx . Accessed 8 Jan 2025. 6. Peres MFP, Sacco S, Pozo-Rosich P, et al. Migraine is the most disabling neurological disease among children and adolescents, and second after stroke among adults: a call to action. Cephalalgia. 2024;44:03331024241267309. 10.1177/03331024241267309. [ DOI ] [ PubMed ] [ Google Scholar ] 7. Stovner LJ, Hagen K, Linde M, Steiner TJ. The global prevalence of headache: an update, with analysis of the influences of methodological factors on prevalence estimates. J Headache Pain. 2022;23:34. 10.1186/s10194-022-01402-2. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 8. Steinmetz JD, Seeher KM, Schiess N, et al. Global, regional, and national burden of disorders affecting the nervous system, 1990–2021: a systematic analysis for the Global Burden of Disease study 2021. Lancet Neurol. 2024;23:344–81. 10.1016/S1474-4422(24)00038-3. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 9. Singh G, Sharma M, Kumar GA, et al. The burden of neurological disorders across the states of India: the Global Burden of Disease Study 1990–2019. Lancet Glob Health. 2021;9:e1129–44. 10.1016/S2214-109X(21)00164-9. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 10. Sudershan A, Pushap AC, Younis M, et al. Neuroepidemiology study of headache in the region of Jammu of north Indian population: a cross-sectional study. Front Neurol. 2023;13:1030940. 10.3389/fneur.2022.1030940. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 11. Puledda F, Sacco S, Diener HC, et al. International Headache Society global practice recommendations for the acute pharmacological treatment of migraine. Cephalalgia. 2024;44:03331024241252666. 10.1177/03331024241252666. [ DOI ] [ PubMed ] [ Google Scholar ] 12. Ailani J, Burch RC, Robbins MS. The American Headache Society consensus statement: update on integrating new migraine treatments into clinical practice. Headache. 2021;61:1021–39. 10.1111/head.14153. [ DOI ] [ PubMed ] [ Google Scholar ] 13. Lipton RB, Marcus SC, Shewale AR, Dodick DW, Viswanathan HN, Doshi JA. Acute treatment patterns in patients with migraine newly initiating a triptan. Cephalalgia. 2020;40:437–47. 10.1177/0333102420905307. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 14. Rimmele F, Müller B, Becker-Hingst N, et al. Medication adherence in patients with cluster headache and migraine: an online survey. Sci Rep. 2023;13:4546. 10.1038/s41598-023-30854-y. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 15. Chowdhury D, Krishnan A, Duggal A, Amarchand R, Husøy A, Steiner TJ. Headache prevalence and demographic associations in the Delhi and National Capital Region of India: estimates from a cross-sectional nationwide population-based study. J Headache Pain. 2024;25:108. 10.1186/s10194-024-01814-2. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 16. Rapoport AM, Bonner JH, Lin T, et al. Remote electrical neuromodulation (REN) in the acute treatment of migraine: a comparison with usual care and acute migraine medications. J Headache Pain. 2019;20:83. 10.1186/s10194-019-1033-9. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 17. Clark O, Mahjoub A, Osman N, Surmava AM, Jan S, Lagman-Bartolome AM. Non-invasive neuromodulation in the acute treatment of migraine: a systematic review and meta-analysis of randomized controlled trials. Neurol Sci. 2022;43:153–65. 10.1007/s10072-021-05664-7. [ DOI ] [ PubMed ] [ Google Scholar ] 18. Theranica. Theranica enters into agreement with Dr. Reddy’s for commercializing Nerivio® in India [press release]. Netanya, Israel: Theranica Bio-Electronics Ltd; 2023 Jan 10. https://www.nerivio.com/news-press/theranica-enters-into-agreement-with-dr-reddys-for-commercializing-nerivio-r-in-india . Accessed 7 Jan 2025. 19. Tepper SJ, Rabany L, Cowan RP, et al. Remote electrical neuromodulation for migraine prevention: a double-blind, randomized, placebo-controlled clinical trial. Headache. 2023;63:377–89. 10.1111/head.14469. [ DOI ] [ PubMed ] [ Google Scholar ] 20. Grosberg B, Rabany L, Vizel M, et al. Effectiveness comparison of remote electrical neuromodulation and standard-care medications for acute treatment of chronic migraine: a post-hoc analysis. Pain Manag. 2022;12:837–44. 10.2217/pmt-2022-0053. [ DOI ] [ PubMed ] [ Google Scholar ] 21. Hershey AD, Irwin SL, Rabany L, et al. Comparison of remote electrical neuromodulation and standard-care medications for acute treatment of migraine in adolescents: a post-hoc analysis. Pain Med. 2021;23:815–20. 10.1093/pm/pnab197. [ DOI ] [ PubMed ] [ Google Scholar ] 22. INS Guidelines. 2024. International Neuromodulation Society. https://www.neuromodulation.com/ins-guidelines . Accessed 8 Jan 2025 23. Central Drugs Standard Control Organisation, 2023. File no. HQ/MD/2023/000012. Dated 30 Nov 2023. Accessed 14 Aug 2025. 24. Alnajjar AZ, Mustafa MM, Abdelsalam OK, et al. Efficacy and safety of remote electrical neuromodulation in migraine: a comprehensive systematic review and meta-analysis. BMC Neurol. 2025;25:291. 10.1186/s12883-025-04291-5. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 25. Migraine Neuromodulation Devices: Nerivio vs. GammaCore vs. Cefaly vs. Spring TMS. Virtual Headache Specialist. 2025. https://virtualheadachespecialist.com/migraine-and-cluster-headache-neuromodulatory-devices-what-are-the-differences-do-they-really-work-and-which-is-best-for-you/ . Accessed 14 Aug 2025. 26. Cowan R, Stark-Inbar A, Rabany L, et al. Clinical benefits and economic cost-savings of remote electrical neuromodulation (REN) for migraine prevention. J Med Econ. 2023;26:656–64. [ DOI ] [ PubMed ] [ Google Scholar ] 27. Song D, Li P, Wang Y, Cao J. Noninvasive vagus nerve stimulation for migraine: a systematic review and meta‑analysis of randomized controlled trials. Front Neurol. 2023;14:1190062. 10.3389/fneur.2023.1190062. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 28. Oxford Centre for Evidence-Based Medicine (OCEBM). Levels of evidence. 2009. Oxford: Centre for Evidence-Based Medicine; 2009. https://www.cebm.ox.ac.uk/resources/levels-of-evidence/oxford-centre-for-evidence-based-medicine-levels-of-evidence-march-2009 . Accessed 8 Jan 2025. 29. Handbook for grading the quality of evidence and the strength of recommendations using the GRADE approach. 2013. https://gdt.gradepro.org/app/handbook/handbook.html . Accessed 8 Jan 2025. 30. Diener HC, Tassorelli C, Dodick DW, et al. Guidelines of the International Headache Society for controlled trials of acute treatment of migraine attacks in adults: fourth edition. Cephalalgia. 2019;39:687–710. 10.1177/0333102419828967. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 31. Versijpt J, Deligianni C, Hussain M, et al. European Headache Federation (EHF) critical re-appraisal and meta-analysis of oral drugs in migraine prevention - part 4: propranolol. J Headache Pain. 2024;25:119. 10.1186/s10194-024-01826-y. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 32. Young WB, Rozen TD. Preventive treatment of migraine: effect on weight. Cephalalgia. 2005;25:1–11. 10.1111/j.1468-2982.2004.00819.x. [ DOI ] [ PubMed ] [ Google Scholar ] 33. Lipton RB, Pozo-Rosich P, Blumenfeld AM, et al. Rates of response to atogepant for migraine prophylaxis among adults: a secondary analysis of a randomized clinical trial. JAMA Netw Open. 2022;5:e2215499. 10.1001/jamanetworkopen.2022.15499. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 34. Demaagd G. The pharmacological management of migraine, part 1: overview and abortive therapy. PT. 2008;33:404–16. [ PMC free article ] [ PubMed ] [ Google Scholar ] 35. Pini LA, Cottafavi K, Ferri P. The nursing role in the management of medication overuse headache: realities and prospects. Brain Sci. 2024;14:600. 10.3390/brainsci14060600. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 36. Turankar T, Sorte A, Wanjari MB, Chakole S, Sawale S. Relation and treatment approach of migraine in pregnancy and breastfeeding. Cureus. 2023;15(3):e36828. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 37. Lazaro-Hernandez C, Caronna E, Rosell-Mirmi J, et al. Early and annual projected savings from anti-CGRP monoclonal antibodies in migraine prevention: a cost-benefit analysis in the working-age population. J Headache Pain. 2024;25:21. 10.1186/s10194-024-01727-0. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 38. Ha H, Gonzalez A. Migraine headache prophylaxis. Am Fam Physician. 2019;99:17–24. [ PubMed ] [ Google Scholar ] 39. Modi S, Lowder DM. Medications for migraine prophylaxis. Am Fam Physician. 2006;73:72–8. [ PubMed ] [ Google Scholar ] 40. D’Amico D, Tepper SJ. Prophylaxis of migraine: general principles and patient acceptance. Neuropsychiatr Dis Treat. 2008;4:1155–67. 10.2147/ndt.s3497. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 41. Goeddertz BK. Patient education for treatment and prophylaxis of migraine. 2008. Grand Forks (ND): University of North Dakota; 2008. https://commons.und.edu/theses/4727 . Accessed 8 Jan 2025. 42. Tzankova V, Becker WJ, Chan TLH. Pharmacologic prevention of migraine. CMAJ. 2023;195:E187–92. 10.1503/cmaj.221607. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 43. Sprenger T, Viana M, Tassorelli C. Current prophylactic medications for migraine and their potential mechanisms of action. Neurotherapeutics. 2018;15:313–23. 10.1007/s13311-018-0621-8. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 44. VanderPluym J, Evans RW, Starling AJ. Long-term use and safety of migraine preventive medications. Headache. 2016;56:1335–43. 10.1111/head.12891. [ DOI ] [ PubMed ] [ Google Scholar ] 45. Ailani J, Rabany L, Tamir S, Ironi A, Starling A. Real-world analysis of remote electrical neuromodulation (REN) for the acute treatment of migraine. Front Pain Res. 2022;2:753736. 10.3389/fpain.2021.753736. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 46. Nierenburg H, Vieira JR, Lev N, et al. Remote electrical neuromodulation for the acute treatment of migraine in patients with chronic migraine: an open-label pilot study. Pain Ther. 2020;9:531–43. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 47. Blue Cross Blue Shield of Massachusetts. Remote electrical neuromodulation for migraine. 2023. Boston (MA). 2023. https://www.bluecrossma.org/medical-policies/sites/g/files/csphws2091/files/acquiadam-assets/145%20Remote%20Electrical%20Neuromodulation%20for%20Migraine.pdf . Accessed 8 Jan 2025. 48. Monteith TS, Stark-Inbar A, Shmuely S, et al. Remote electrical neuromodulation (REN) wearable device for adolescents with migraine: a real-world study of high-frequency abortive treatment suggests preventive effects. Front Pain Res. 2023;4:1247313. 10.3389/fpain.2023.1247313. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 49. American Headache Society. Migraine, pregnancy, and lactation Mount Royal (NJ). https://americanheadachesociety.org/resources/primary-care/migraine-pregnancy-and-lactation . Accessed 8 Jan 2025. 50. Silberstein SD. Preventive migraine treatment. Continuum (Minneap Minn). 2015;21(4 Headache):973–89. 10.1212/CON.0000000000000199. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 51. Yarnitsky D, Dodick DW, Grosberg BM, et al. Remote electrical neuromodulation (REN) relieves acute migraine: a randomized, double-blind, placebo-controlled, multicenter trial. Headache. 2019;59:1240–52. 10.1111/head.13551. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 52. Singh S, Srinivasan AV, Banerjee TK, et al. Indian consensus on the role of amitriptyline in migraine prophylaxis. Cureus. 2024. 10.7759/cureus.54270. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 53. Cooper W, Doty EG, Hochstetler H, Hake A, Martin V. The current state of acute treatment for migraine in adults in the United States. Postgrad Med. 2020;132:581–9. 10.1080/00325481.2020.1767402. [ DOI ] [ PubMed ] [ Google Scholar ] 54. Aguilar-Shea AL, Membrilla MJA, Diaz-de-Teran J. Migraine review for general practice. Aten Primaria. 2022;54:102208. 10.1016/j.aprim.2021.102208. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 55. Ravishankar K, Chakravarty A, Chowdhury D, Shukla R, Singh S. Guidelines on the diagnosis and the current management of headache and related disorders. Ann Indian Acad Neurol. 2011;14:40. 10.4103/0972-2327.83100. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 56. Bangale N, Erande S, Sundar KS, et al. Deciphering optimal management options for headache. IP Indian J Neurosci. 2023;8:234–7. 10.18231/j.ijn.2022.048. [ Google Scholar ] 57. Bhave K, Tondare S, Pandit P, Patankar R. Drug use pattern and quality of life in patients with migraine at a tertiary care hospital in India: an observational study. Natl J Physiol Pharm Pharmacol. 2022. 10.5455/njppp.2022.12.0314520220002042022. [ Google Scholar ] 58. Jackson JL, Kuriyama A, Kuwatsuka Y, et al. Beta-blockers for the prevention of headache in adults, a systematic review and meta-analysis. PLoS ONE. 2019;14:e0212785. 10.1371/journal.pone.0212785. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 59. Radojičić A, Milićević A, Ždraljević M, et al. Prevalence and awareness of medication overuse headache among undergraduate students at the university of Belgrade. Brain Sci. 2024;14:938. 10.3390/brainsci14090938. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 60. Ornello R, Caponnetto V, Ahmed F, et al. Evidence-based guidelines for the pharmacological treatment of migraine, summary version. Cephalalgia. 2025;45:3331024251321500. 10.1177/03331024251321500. [ DOI ] [ PubMed ] [ Google Scholar ] 61. Shafqat R, Flores-Montanez Y, Delbono V, Nahas SJ. Updated evaluation of IV dihydroergotamine (DHE) for refractory migraine: patient selection and special considerations. J Pain Res. 2020;13:859–64. 10.2147/JPR.S203650. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 62. Pavitt S, Morris C, Shin L, et al. Tolerability of repetitive dihydroergotamine infusions paired with an adjustment in preventive treatment strategy in chronic headache disorders in children and youth. J Headache Pain. 2025;26:93. 10.1186/s10194-025-02035-x. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 63. Wang VS, Kosman J, Yuan H, et al. Safety, tolerability, and effectiveness of repetitive intravenous dihydroergotamine for refractory chronic migraine with cardiovascular risk factors: a retrospective study. Headache. 2023;63:1251–8. 10.1111/head.14636. [ DOI ] [ PubMed ] [ Google Scholar ] 64. Voloshin AG, Moiseeva IV. Combined interventional treatment of refractory chronic migraine. SN Comprehen Clin Med. 2021;3:1320–6. 10.1007/s42399-021-00868-6. [ Google Scholar ] 65. Yarnitsky D, Volokh L, Ironi A, et al. Nonpainful remote electrical stimulation alleviates episodic migraine pain. Neurology. 2017;88:1250–5. 10.1212/WNL.0000000000003760. [ DOI ] [ PubMed ] [ Google Scholar ] 66. BaniHani H, Lampl C, MaassenvandenBrink A, et al. The role of community pharmacists in managing common headache disorders, and their integration within structured headache services: position statement on behalf of the European Headache Federation (EHF) and Lifting The Burden (LTB: the Global Campaign against Headache), with the formal endorsement of the International Pharmaceutical Federation. J Headache Pain. 2025;26:100. 10.1186/s10194-025-02021-3. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 67. Grosberg B, Rabany L, Lin T, et al. Safety and efficacy of remote electrical neuromodulation for the acute treatment of chronic migraine: an open-label study. Pain Rep. 2021;6:e966. 10.1097/PR9.0000000000000966. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 68. Marmura MJ, Lin T, Harris D, Ironi A, Rosen NL. Incorporating remote electrical neuromodulation (REN) into usual care reduces acute migraine medication use: an open-label extension study. Front Neurol. 2020;11:226. 10.3389/fneur.2020.00226. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 69. Alnajjar F, Kalantari A, Shalaby A, Teo J, Al-Jumeily D, Hussain A. A comprehensive review of remote electrical neuromodulation (REN): efficacy, safety, and future perspectives. Front Pain Res (Lausanne). 2025;6:1525464. 10.3389/fpain.2025.1525464. [ Google Scholar ] 70. Hershey AD, Lin T, Gruper Y, et al. Remote electrical neuromodulation for acute treatment of migraine in adolescents. Headache. 2021;61:310–7. 10.1111/head.14042. [ DOI ] [ PubMed ] [ Google Scholar ] 71. American Headache Society. Update on noninvasive neuromodulation devices for headache treatment: consensus statement. Pract Neurol. 2023. https://practicalneurology.com/diseases-diagnoses/headache-pain/update-on-noninvasive-neuromodulation-devices-for-headache-treatment/32129/ . Accessed 14 Aug 2025. 72. Alsaadi T, Kayed DM, Al-Madani A, et al. Acute treatment of migraine: expert consensus statements from the United Arab Emirates (UAE). Neurol Ther. 2024;13:257–81. 10.1007/s40120-023-00576-4. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 73. Buse DC, Rabany L, Lin T, Ironi A, Connelly MA, Bickel JL. Combining guided intervention of education and relaxation (GIER) with remote electrical neuromodulation (REN) in the acute treatment of migraine. Pain Med. 2022;23:1544–9. 10.1093/pm/pnac021. [ DOI ] [ PubMed ] [ Google Scholar ] 74. Peretz A, Stark-Inbar A, Harris D, et al. Safety of remote electrical neuromodulation for acute migraine treatment in pregnant women: A retrospective controlled survey-study. Headache. 2023; 63:968–70. 10.1111/head.14586 [ DOI ] [ PubMed ] [ Google Scholar ] 75. Synowiec A, Stark-Inbar A, Weinstein M, Ironi A, Mauskop A. One-year consistent safety, utilization, and efficacy assessment of remote electrical neuromodulation (REN) for migraine treatment. Adv Ther. 2024;41:170–81. 10.1007/s12325-023-02697-6. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 76. Nierenburg H, Rabany L, Lin T, et al. Remote electrical neuromodulation (REN) for the acute treatment of menstrual migraine: a retrospective survey study of effectiveness and tolerability. Pain Ther. 2021;10:1245–53. 10.1007/s40122-021-00276-7. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] Associated Data This section collects any data citations, data availability statements, or supplementary materials included in this article. Supplementary Materials Supplementary file1 (PDF 263 KB) (263.2KB, pdf) Data Availability Statement All data generated or analyzed during this study are included in this published article/supplementary information files. 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