Abstract
Introduction
Migraine, characterized by recurrent headaches and often accompanied by other symptoms like nausea, vomiting, and sensitivity to light and sound, significantly impacts patients’ quality of life (QoL) and daily functioning. The global burden of migraines is reflected not only in terms of reduced QoL but also in the form of increased healthcare costs and missed work or school days. While UAE (United Arab Emirates)-specific consensus-based recommendations for the effective use of preventive calcitonin gene-related peptide (CGRP)-based migraine therapies have been published previously, an absence of such regional guidance on the management of acute migraine represents a gap that needs to be urgently addressed.
Methods
A task force of eight neurologists from the UAE with expertise in migraine management conducted a comprehensive literature search and developed a set of expert statements on the management of acute migraine that were specific to the UAE context. To ensure diverse perspectives are considered, a Delphi panel comprising 16 neurologists plus the task force members was set up. Consensus was achieved using a modified Delphi survey method. Consensus was predefined as a median rating of 7 or higher without discordance (if > 25% of the Delphi panelists rate an expert statement as 3 or lower on the Likert scale). Expert statements achieving consensus were adopted.
Results
The Modified Delphi method was used successfully to achieve consensus on all nine expert statements drafted by the task force. These consensus statements aim to provide a comprehensive guide for UAE healthcare professionals in treating acute migraine. The statements cover all aspects of acute migraine treatment, including what goals to set, the timing of treatment, treatment strategy to use in case of inadequate response to triptans, safety aspects of combining gepants for acute attacks with preventive CGRP-based therapies, special population (pregnant and pediatric patients) considerations, and the management of the most bothersome symptoms (MBS).
Conclusions
Adopting these consensus statements on the treatment of acute migraine can help enhance patient care, improve outcomes, and standardize treatment practices in the UAE. The collaborative effort of experts with diverse experiences in developing these consensus statements will strengthen the credibility and applicability of these statements to various healthcare settings in the country.
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Effective acute migraine management can contribute to a more effective healthcare system by reducing the overall economic burden associated with untreated or poorly managed migraine episodes. Optimal treatment of acute migraine is crucial to improve patients’ daily functioning, enhance their mental well-being, and ensure they enjoy a good quality of life (QoL). |
The development of consensus statements by an expert UAE-based panel using a modified Delphi method is a significant step in creating evidence-based guidance for the treatment of acute migraine that integrates the international consensus recommendations with a UAE-specific perspective. |
Adopting these regional consensus statements can help healthcare professionals tailor evidence-based treatments to the specific needs of patients in the UAE. |
Introduction
Migraine is a neurological disorder that causes recurrent and episodic moderate-to-severe headaches [1]. Given its high global prevalence and debilitating effects, the adverse impact of migraine on patients’ quality of life (QoL) cannot be overemphasized. The 2019 Global Burden of Disease (GBD) data attribute a significant burden of neurological disorders to headache disorders, with migraine being ranked the second highest cause of disability worldwide. Also, according to the GBD data, migraine has an estimated global prevalence of around 14–15% [2, 3]. The negative effects of migraine influence all spheres of patients’ lives, hindering their day-to-day activities, affecting cognitive abilities at work sometimes leading to job loss, and impacting social relationships [4].
Migraine has two major types—migraine with aura (previously known as classical/classic migraine), which presents with distinct and transient focal neurological symptoms preceding or occurring with the headache, and migraine without aura (previously known as common migraine). The International Classification of Headache Disorders-3 (ICHD-3) criteria refer to chronic migraine as headaches occurring for at least 15 days/month for more than 3 months and presenting with features of migraine with or without aura on at least 8 days/month [5]. The disease progression rate in migraine, i.e., an increase in headache frequency from less than 15 monthly headache days (MHDs) to 15 or more MHDs, which represents a transition from episodic migraine to chronic migraine, has been estimated to be about 3% per year in population-based studies and around 14% in clinic-based studies [6].
The pathophysiology of migraine is complex and multifactorial, involving a confluence of genetic and environmental factors. Neuroimaging studies have helped to unravel the cortical, subcortical, and brainstem region pathways involved in migraine and led to a better understanding of its neurobiology and the development of novel preventive and acute treatments [7]. Calcitonin gene-related peptide (CGRP), a 37-amino acid neuropeptide, has been identified as an important factor in migraine pathophysiology, facilitating the development of gepants, which are small-molecule CGRP receptor antagonists. Also, ditans, highly lipophilic selective serotonin 5-HT1F receptor agonists, have emerged as potential alternatives to triptans in patients with cardiovascular diseases [8]. Gepants and ditans have now been added to the existing arsenal of available treatments for acute migraine attacks, which include non-steroidal anti-inflammatory drugs (NSAIDs), combination analgesics, ergot alkaloids, and triptans. US Food and Drug Administration (FDA)-approved monoclonal antibodies (mABs) targeting the CGRP pathway (galcanezumab, fremanezumab, eptinezumab, and erenumab) are being increasingly used to prevent migraine attacks owing to their favorable efficacy and tolerability profiles [7].
For optimal management, migraine must be promptly diagnosed in the primary care setting, and eligible patients must be referred to neurologists without delay. However, multiple studies suggest migraine is an underdiagnosed disorder. As a result of the absence of specific diagnostic tests, diagnosis is based solely on clinical manifestations, primarily depending on patients’ recollections and descriptions [9]. In addition to underdiagnosis, several studies suggest that acute and preventive migraine treatment is often suboptimal [9, 10]. Results of the cross-sectional questionnaire-based Eurolight study showed that, of the 2364 adults (from general population-based samples) diagnosed with migraine (definite or probable), only 9.5–18% consulted a general practitioner (GP), and a meager 3.1–15% saw a specialist. Also, only around 3.4–22.4% received triptans, and 1.6–13.7% of those eligible received preventive treatment [10]. Thus, to optimize migraine care and facilitate clinical decisions by GPs, neurologists, and headache specialists, the Danish Headache Society developed a consensus statement in 2021. It has been endorsed by the European Headache Federation (EHF) and the European Academy of Neurology (EAN). The consensus statement comprises a comprehensive ten-step approach that covers the entire spectrum of migraine care from “when to suspect migraine” to “planning long-term follow-up.” It includes acute (see Fig. 1) and preventive treatment recommendations based on efficacy, safety, cost, local availability, and third-party reimbursement policies [11].
The American Headache Society (AHS) also published a consensus statement in 2021, which integrates new acute and preventive therapies into the existing migraine treatment guidelines established by the US Headache Consortium. This update includes five therapies (celecoxib, lasmiditan, remote electrical neuromodulation, rimegepant, and ubrogepant) that the FDA has approved since the publication of the initial guidelines [12].
Along the lines of the observations from the Eurolight study, migraine care in the UAE is also highly fragmented because of the lack of standardized protocols and pathways for diagnosis and treatment. Drug availability, cost, and third-party reimbursement policies often influence therapy choices. Moreover, the level of experience of healthcare practitioners (HCPs) in managing headache disorders is variable and influences their treatment decisions. Without standardized protocols, they opt for different approaches to managing migraine, leading to significant inconsistencies in treatment plans and outcomes. The first step to reducing the fragmentation of migraine care in the UAE would be to establish consensus statements that apply to both GPs and specialists and are based on the healthcare practices, patient demographics, and availability of migraine therapies in the UAE. Developing these statements through the collaborative efforts of experienced specialists in the field can be a valuable step in facilitating effective migraine treatment, improving patient outcomes and QoL, and the overall healthcare system’s efficiency. Well-informed HCPs are more likely to make accurate diagnoses and develop evidence-based, effective treatment plans. UAE-specific consensus statements can help address the local patient population’s unique needs and preferences and allow HCPs to adhere to consistent treatment practices, ensuring uniformity and quality in patient care.
Moreover, by developing these consensus statements, specific knowledge gaps from a regional perspective can be identified to encourage future research efforts and regional real-world data collection. Expert consensus statements tailored to the UAE healthcare system can guide GPs and neurologists on preventive and acute treatments and help them overcome the barriers to migraine diagnosis and treatment. A coherent approach to managing migraine can allow effective utilization of the available therapies while improving patients’ QoL.
To achieve these objectives, an expert panel of eight UAE-based neurologists with expertise in migraine management sought to (1) assess the need for developing such consensus statements, (2) draft expert statements for the acute treatment of migraine by considering the unique regional challenges and the unmet needs of the local patient cohort, and (3) obtain a consensus on these expert statements from a larger panel of specialists with a broad range of expertise and experience in migraine management.
Regional (UAE-specific) consensus-based recommendations for the effective use of preventive CGRP-based migraine therapies have been published previously [13].
Methods
Establishment of a Task Force
Eight neurologists from the UAE with expertise in migraine management, along with members of the Emirates Neurology Society (EMINS), formed a task force to identify key clinical questions based on UAE-specific practice trends and challenges and developed expert consensus statements based on the questions.
Literature Review and the Development of Consensus Statements
Drs. Taoufik Alsaadi, Deeb M Kayed, and Abubaker Al-Madani did a preliminary literature search in September 2023 to collate the relevant acute migraine treatment-related studies, including randomized clinical trials (RCTs), international guideline recommendations, and observational and real-world studies published in peer-reviewed journals. This preliminary search laid the groundwork for all the task force members to identify the most appropriate search keywords and strategize a more comprehensive literature search on the PubMed database. The task force members independently reviewed all the selected scientific and clinical studies and deliberated as a group to identify the key UAE-specific areas that needed to be addressed.
The task force members developed a set of nine expert statements after considering all the challenges related to acute migraine treatment the clinical fraternity in the UAE was facing. The members jointly drafted the expert statements following multiple rounds of online discussion. The statements were further reviewed and finalized in a panel meeting convened on September 24, 2023.
Delphi Survey and Analysis of Results
The task force wanted to ensure that the drafted expert statements reflect diverse perspectives and experiences. Thus, a modified Delphi survey method was chosen to obtain a consensus. Through a nomination and voting process, 16 experienced UAE-based neurologists selected by the task force members were invited to participate in the survey. The 16 neurologists who agreed to participate in the survey and the eight task force members jointly constituted the Delphi expert panel. The survey included the nine expert statements drafted by the task force, which could be rated on a 9-point Likert scale (ranging from 1 = “strongly disagree” to 9 = “strongly agree”). “No opinion” was not provided as an option on the survey.
Discordance was predefined as greater than 25% of the Delphi panelists rating an expert statement as 3 or lower on the Likert scale. Consensus was predefined as a median rating of 7 or higher without discordance. Expert statements achieving consensus were adopted.
The expert consensus statements were critically reviewed using the Oxford Levels of Evidence system to evaluate the quality of supporting evidence and generate a score indicating the strength of the recommendation.
This article is based on previously conducted studies and does not contain any new studies with human participants or animals performed by any of the authors. The study received institutional review board (IRB) approval from the American Center for Psychiatry and Neurology’s IRB ethical exemption, with the reference ACPN_IRB_0058. All experts were authors in the study.
Results
Results of the Delphi Survey on the Expert Statements
The 24 experts of the Delphi panel voted on the nine statements drafted by the task force relating to the acute treatment of migraine in the UAE. Voting was conducted anonymously using Google Forms and allowed the experts to express their opinions honestly without any pressure to conform with the majority. Consensus was achieved on all expert statements based on the a priori criteria (see Fig. 2). Herein, we elaborate on the supporting evidence and the rationale for developing each expert statement.
Consensus statements for acute migraine treatment in the UAE. Level of evidence: 1A, from a meta-analysis of randomized controlled trials; 1B, from at least one randomized controlled trial; 2A, from at least one controlled study without randomization; 2B, from at least one type of quasi-experimental study; 3, from descriptive studies, such as comparative studies, correlation studies, or case–control studies; 4, from expert committee reports or opinions 832 and/or clinical experience of respected authorities. Grade of recommendation: A, directly based on level 1 evidence; B, directly based on level 2 evidence or extrapolated recommendations from level 1 evidence; C, directly based on level 3 evidence or extrapolated recommendation from level 1 or level 2 evidence; D, directly based on level 4 evidence or extrapolated recommendation from level 2 or level 3 evidence
Is There a Need to Develop UAE-Specific Consensus Statements on Acute Treatment of Migraine?
As our understanding of migraine pathophysiology evolves, new treatments to manage it are becoming available, prompting international societies like EHF/EAN and AHS to update their recommendations on migraine management. Multiple physician-related and treatment-related factors affect clinical outcomes in migraine. The level of experience and training of HCPs in treating headache disorders, their affiliations (private vs. public sector), and access to new treatments influence clinical decisions. Also, treatment costs and reimbursement policies are significant in decision-making and can hinder optimal care.
The benefits of having a unified approach validated by experts in all steps of migraine treatment—from diagnosis to follow-up care—can be manifold. It can (1) help HCPs optimize migraine treatments early in the course of care, reducing the financial burden of migraine on patients and the healthcare system; (2) provide government healthcare authorities a guideline to formulate regulations and policies regarding treatment costs of expensive therapies like gepants and ditans; and (3) facilitate claim approvals by third-party insurance providers, ensuring patients do not have to compromise on getting effective treatments. Establishing UAE-specific consensus statements for all steps involved in migraine management would be a crucial first stride toward achieving a unified and comprehensive approach to migraine care.
UAE-specific consensus-based recommendations on using the new CGRP-based therapies for migraine prevention were recently published [13]. They will guide physicians to choose the most appropriate prophylactic therapy for their patients, improving clinical outcomes and lowering healthcare costs due to therapy failures. However, a similar expert consensus in the acute treatment of migraine that is specific to the UAE patient population and healthcare system is lacking.
Expert Statement 1:
We propose to establish consensus statements to guide the use of acute migraine therapies in the UAE.
The task force considers establishing consensus statements on acute migraine therapies in the UAE as signifying a proactive approach to enhancing treatment outcomes and minimizing unnecessary healthcare costs. The statements will have to be based on the specific resources available to the HCPs in the UAE, thus making them realistic and practical. Additionally, they will have to align with the principles of evidence-based medicine and patient-centered care with the primary goal of improving treatment outcomes. The positive impact on the UAE healthcare system in terms of long-term cost savings will be an added benefit.
The expert panel agreed that there is a need to establish consensus statements guiding the use of acute migraine therapies in the UAE to improve patient outcomes and enhance the quality of care (see Fig. 2).
Who Should Be Offered Acute Migraine Therapy?
Migraine attacks are associated with unpleasant and disabling symptoms like nausea, vomiting, photophobia, and phonophobia accompanying severe headaches that can last from 4 to 72 h [14]. These symptoms adversely affect patients’ health-related QoL, impacting their social and psychological well-being. Repeated migraine attacks also cause stress in patients, contributing to an increased prevalence of psychological disorders such as depression and anxiety [15]. Furthermore, stress is the most commonly reported factor triggering migraine attacks. Alcohol consumption, sleep disturbances, eating disorders, and hormonal changes, such as those during menstruation, are other reported triggers [16]. Some of these triggers are modifiable, but not all. Thus, avoiding migraine-predisposing triggers may not always be feasible.
Given the significant impact of acute migraine attacks on patients’ daily lives, the EHS/EAN consensus statement recommends offering acute therapy to all those who experience them. The consensus statement recommends using NSAIDs like ibuprofen, acetylsalicylic acid, or diclofenac sodium as first-line and triptans as second-line therapies. Ditans and gepants are reserved as third-line options if triptan therapy fails or is contraindicated [11]. The AHS updated consensus statement also indicates acute therapeutic intervention (oral or non-oral pharmacological and/or non-pharmacological) in all patients diagnosed with migraine. The AHS consensus statement lists specific criteria for initiating treatment with newer pharmacological therapies like gepants and ditans, and non-pharmacological interventions like neuromodulatory devices.
Expert Statement 2
All patients with a confirmed diagnosis of migraine should be offered acute pharmacological therapy.
The task force is of the view that the AHS and EHS/EAN consensus statements recommending that physicians offer acute pharmacological therapy to all patients diagnosed with migraine based on the ICHD3 criteria is a fundamental aspect of providing effective migraine care.
The expert panel also agreed that offering acute pharmacological therapy to all patients with a confirmed migraine diagnosis is an evidence-based approach to managing acute attacks (see Fig. 2). It can provide relief from pain and other symptoms during a migraine episode. Variables like cost and reimbursement policies affect accessibility to ditans and gepants in the UAE. Encouraging physicians to have an open dialogue with patients about the pros and cons of all clinically viable options can improve treatment adherence and outcomes.
What Should Be the Goals of Acute Migraine Therapy?
The clinical presentation of migraine is highly heterogeneous and dynamic. The acute attacks manifest as headaches of varying frequency, duration, and severity that can change with time. Thus, the extent of physical, social, and psychological disability these attacks cause is also variable. This wide variation in presentation, even in the same individual, calls for a personalized approach to treatment. Treatment success depends on choosing the right treatment plan based on each patient’s specific clinical profile. Establishing realizable acute migraine therapy goals broadly applicable to a wide patient spectrum can help patients and physicians mutually identify those they would like to achieve. Setting goals can guide physicians in curating the best-suited treatment plan for their patients.
Cultural and regional factors impact patient and physician preferences and opinions, which, in turn, influence migraine treatment choice. Differences in patient referral systems also contribute to heterogeneity in acute and preventive migraine treatment prescribing practices across countries [17]. Regional studies on such practice trends are lacking in the UAE, making it challenging to establish UAE-specific treatment goals. The 2021 updated AHS consensus statement has established acute and preventive migraine treatment goals to help physicians decide the best course of action and set realistic patient expectations.
We believe the short- and long-term acute migraine therapy goals transcend these regional differences in prescribing practices and apply to all patient populations. Thus, the acute migraine treatment goals established by the AHS in its consensus statement can also be adopted by the HCPs in the UAE (see Fig. 3).
![figure 3](http://media.springernature.com/lw685/springer-static/image/art%3A10.1007%2Fs40120-023-00576-4/MediaObjects/40120_2023_576_Fig3_HTML.png)
Adapted from Ailani J, Burch RC, Robbins MS. The American Headache Society consensus statement: update on integrating new migraine treatments into clinical practice. Headache: The Journal of Head and Face Pain. 2021;61(7):1021–1039
Goals for the acute treatment of patients with migraine set by AHS in its updated consensus statement (2021).
Expert Statement 3
In individuals with migraine, we suggest adopting the AHS goals of treatment while considering all the options for managing acute attacks for those affected.
The task force concludes that by incorporating the AHS goals while considering all available options for managing acute attacks, HCPs can provide comprehensive and individualized care to patients.
The expert panel agreed that the acute migraine treatment goals set by the AHS also apply to UAE physicians and patients and can be adopted to help devise optimal treatment plans and assess therapy success or failure (see Fig. 2).
At Which Stage of a Migraine Attack Should Patients Be Asked to Take Acute Medications?
Whether patients with migraine should take acute medications when the headache is still mild or only after it becomes moderate or severe is a subject of contention. There is a likelihood that patients who usually experience migraines without aura may confuse other types of headaches as a migraine during the early stage when the pain intensity is mild. Thus, the rationale for recommending late intervention in an acute migraine attack, only when the pain intensity has reached moderate or severe levels, is to ensure that non-migraine headaches are not treated with migraine-specific medications [18]. However, several clinical studies have shown that early intervention in an acute migraine attack with migraine-specific medications, like a triptan or gepant, is more effective than late intervention.
A randomized, multicenter, multinational, double-blind, placebo-controlled trial on 403 migraineurs showed that 53% of those who were treated in the mild headache phase were pain-free at 2 h compared to 38% of those who were treated after the pain intensity had reached moderate or severe levels (p = 0.03) [19]. In the first phase of TEMPO, a French prospective, multicenter, two-phase study enrolling 144 patients, 52.8% of the “early dosers” achieved freedom from pain at 2 h in at least two of three attacks compared to only 30.2% of the “late dosers” (p < 0.01). The result of the second-phase study also demonstrated an improved triptan treatment efficacy when the physicians advised patients to switch from late dosing to early dosing [20].
Cutaneous allodynia is pain caused by non-noxious stimuli to normal skin. It is highly prevalent in patients with migraine and indicates central sensitization and an increased risk of chronification [21]. Studies on rat models have shown that early treatment with triptans before cutaneous allodynia gets established in patients with migraine prone to it can prevent the initiation of central sensitization and avert an attack, making them pain-free. On the other hand, late treatment with a triptan, after cutaneous allodynia gets established, proves to be inadequate in reversing central sensitization [22].
In a phase 3, open-label, dose-blinded trial by Lipton et al., the 2-h freedom from pain rates were significantly higher when acute attacks were treated with ubrogepant when the pain was mild compared to when the pain was moderate or severe. The improved efficacy outcome (2-h freedom from pain) was seen with 50 mg (47.1% vs. 23.6%; mild pain vs. moderate/severe pain, respectively; p < 0.0001) and 100 mg (55.2% vs. 26.1%; mild pain vs. moderate/severe pain, respectively; p < 0.0001) doses of ubrogepant. Moreover, rates of 2-h freedom from other migraine-associated symptoms like nausea, photophobia, and phonophobia were also higher in the cohort treated during the mild headache stage compared to the moderate/severe stage cohort [23].
The PRODROME trial was a multicenter, randomized, double-blind, placebo-controlled crossover trial enrolling adults experiencing 2–8 migraine headaches of moderate-to-severe pain intensity. Data presented from this trial during the 2023 annual American Academy of Neurology (AAN) meeting demonstrated favorable results with ubrogepant treatment [24,25,26]. The study showed that patients could identify migraine attacks on the basis of the common prodromal symptoms they experienced [25]. The primary endpoint of the trial was an absence of moderate or severe intensity headache 24 h post-treatment in the prodromal phase of the migraine, and it was achieved by 45.5% of the ubrogepant-treated participants compared to 28.6% of the placebo-treated participants (p < 0.0001) [24].
Available evidence suggests that early rather than late intervention during an acute migraine attack can improve outcomes, including freedom from pain and other migraine-associated symptoms.
Expert Statement 4
We believe that early use of acute medications, regardless of the severity of the attack, would result in a better response for most individuals with migraine.
Pain is a subjective experience, and classifying it objectively as mild, moderate, or severe is challenging. An acute attack may sometimes begin with a headache of moderate to severe intensity. Thus, the task force carefully drafted this statement to recommend an “early use of acute medication, regardless of the severity of the attack” instead of using mild, moderate, or severe pain intensity to indicate when during the attack to treat.
On the basis of the a priori criteria, this statement can be adopted, as 96% of the panel agreed with the early intervention strategy during an acute attack, and none disagreed. However, it should be noted that one panelist had a neutral opinion (see Fig. 2).
What is the Best Protocol to Manage Acute Attacks: Stepwise or Stratified?
Acute migraine management encompasses non-specific symptomatic treatment with simple or combination analgesics (primarily NSAIDs) and migraine-specific treatment with triptans, gepants, or ditans. Physicians can employ two strategies while prescribing these treatments for acute attacks—stepwise or stratified.
The stepwise approach involves climbing up the treatment ladder irrespective of the attack severity, starting with the basic NSAIDs and progressively escalating the treatment to migraine-specific medications if the NSAIDs are ineffective, either within an attack or across different attacks. The stratified approach uses attack severity to guide treatment choice; patients are prescribed analgesics or a migraine-specific medication after gauging the attack severity [27].
The EHF/EAN consensus statement recommends an individualized stepped-care approach across migraine attacks. It recommends NSAIDs as first-line treatment for three consecutive episodes. Triptans are recommended second in line if NSAIDs are ineffective. Treatment failure of all triptans is an indication for considering gepants or ditans [11]. On the other hand, the AHS consensus statement recommends a stratified treatment approach based on the severity of attacks (see Fig. 4) [12].
![figure 4](http://media.springernature.com/lw685/springer-static/image/art%3A10.1007%2Fs40120-023-00576-4/MediaObjects/40120_2023_576_Fig4_HTML.png)
Adapted from Ailani J, Burch RC, Robbins MS. The American Headache Society consensus statement: update on integrating new migraine treatments into clinical practice. Headache: The Journal of Head and Face Pain. 2021;61(7):1021–1039
AHS consensus statement: Evidence-based treatments in the management of acute migraine attacks. *Criteria for initiating gepants and ditans for acute treatment: Prescribed by a licensed physician, patient ≥ 18 of age with a diagnosis of migraine (with or without aura) or chronic migraine. Either contraindication to or inability to tolerate triptans OR inadequate response to two or more oral triptans as assessed using a validated acute treatment patient-reported outcome questionnaire or on clinician attestation.
Long-term suboptimal treatment of episodic migraine carries the risk of chronification, underscoring the importance of choosing the right approach early on to prevent disease progression [6, 28].
Lipton et al. conducted the Disability in Strategies of Care (DISC), a randomized, controlled, parallel-group trial, to compare the benefits of the three acute treatment strategies (stratified, stepwise care within attacks, and stepwise care across attacks) in 88 clinical centers spread across 13 countries. The results of this trial showed that the stratified care approach was associated with better clinical outcomes (headache response and disability time per treated attack) than the other two approaches. The study found the stratified approach patient-centric, allowing flexibility to match the therapy to patients’ attack severity. On the other hand, the stepwise approach delayed pain relief and was associated with low levels of patient satisfaction [27]. The stratified approach has also been shown to be more cost-effective for the primary healthcare system than the stepwise strategy [29].
The stepwise approach may allow better utilization of resources, especially in resource-constrained situations, as the more expensive migraine-specific treatments are reserved only for those in whom the simple analgesics are ineffective. However, this advantage comes at the cost of prolonging disability and functional restoration. Also, in real-world clinical practice, most patients approach physicians only after they fail to get any relief with common analgesics and thus they are not treatment-naïve.
Expert Statement 5
We propose to follow a stratified care approach, taking into consideration the attack severity, patient’s comorbidity, and contraindications to various acute therapy medications.
The stepwise approach to acute treatment of migraine attacks potentially protects patients against unnecessary exposure to migraine-specific medications and their side effects as they are prescribed only after ensuring that the attacks are non-responsive to simple or combination analgesics. However, this approach requires substantial trial and error and frequent follow-up consultations before an optimal treatment is found. Moreover, this strategy increases the risk of patients losing confidence in the therapy and not following up regularly, resulting in significant morbidity and disability. On the basis of the evidence available, the task force believes that stratifying treatment based on attack severity, patient comorbidities, and contraindications is a more patient-centric approach that can produce better long-term outcomes.
The entire expert panel also agreed/strongly agreed that a stratified, instead of a stepwise, approach to manage acute attacks would be more likely to improve treatment outcomes while also being cost-effective in the long run (see Fig. 2).
Where Do Gepants and Ditans Fit in the Acute Migraine Treatment Algorithm?
CGRP, a potent cerebral vasodilator discovered by Amara et al. nearly 40 years ago, has emerged as a major player in the discovery of novel migraine-specific therapies intended for acute and preventive use [30, 31]. CGRP-targeted therapies include monoclonal antibodies (erenumab, fremanezumab, galcanezumab, and eptinezumab) and small molecule gepants (ubrogepant, rimegepant, zavegepant, and atogepant).
In ACHIEVE II, a phase 3, multicenter, double-blind, placebo-controlled, single-attack, RCT, ubrogepant was shown to provide significantly greater rates of 2-h pain freedom (21.8% vs. 14.3%, ubrogepant 50 mg vs. placebo, respectively; p = 0.01) and absence of MBS at 2 h (38.9% vs. 27.4%, ubrogepant 50 mg vs. placebo, respectively; p = 0.01) compared to placebo [32]. Similarly, a multicenter, double-blind, phase 3 RCT on rimegepant also showed favorable results—19.6% of patients receiving rimegepant were pain-free at 2 h compared to 12% of those receiving placebo (p < 0.001), and 37.6% in the rimegepant group were free from MBS at 2 h versus 25.2% in the placebo group (p < 0.001) [33].
Lasmiditan is a selective 5-HT1F receptor agonist acting on the trigeminal system. As a result of its low affinity for 5-HT1B receptors, it is not vasoconstrictive, making it a reasonable option in patients with contraindications to triptans [34]. In a prospective, double-blind, multicenter, phase 3 RCT by Goadsby et al., 2-h freedom from pain (38.8% vs. 21.3%, lasmiditan 200 mg vs. placebo; p < 0.001) and 2-h freedom from MBS (48.7% vs. 33.5%, lasmiditan 200 mg vs. placebo; p < 0.001) rates were significantly higher in the lasmiditan-treated cohort than the placebo-treated cohort [35].
Among the three gepants (ubrogepant, rimegepant, and zavegepant) approved by the FDA for the acute treatment of migraine attacks, only ubrogepant and rimegepant are available in the UAE. Lasmiditan, the only FDA-approved ditan, is also approved for acute migraine treatment in the UAE (see Fig. 5).
Although the availability of gepants and ditans opens new avenues in treating acute migraine attacks, their place in the treatment algorithm remains unclear because of the lack of head-to-head comparison trials with triptans. The EHS/EAN consensus statement, which recommends a stepwise approach for treating acute attacks, places them third in line after NSAIDs, triptans, and a combination of triptans with fast-acting NSAIDs. They are recommended only after an “adequate trial period” with all available triptans, defined as “no or insufficient therapeutic response in at least three consecutive attacks” [11]. The AHS consensus statement recommends gepants and ditans for treating moderate or severe attacks and mild-to-moderate attacks not responding to non-specific therapy, provided the criteria in Fig. 4 are met. One of the criteria is a contraindication to or an inability to tolerate or an inadequate response to two or more oral triptans [12]. However, defining what constitutes triptan failure is crucial before this recommendation can be applied in clinical practice.
An inadequate response has been observed in approximately 30–40% of patients taking triptans. Leroux et al. performed a systematic literature review of studies published from January 1995 to May 2019. They identified 35 publications (22 RCTs and open-label studies and 13 observational studies) to broadly understand the definitions of treatment failure and outcomes in patients showing insufficient efficacy and/or tolerability to triptans [36].
The definition of insufficient efficacy and/or tolerability of triptans was based on variable outcomes that were predefined in the study protocols—e.g., inadequate/unsatisfactory response (e.g., patient-reported outcomes), reasons for discontinuation (e.g., due to slow onset of action, inconsistent response, poor overall efficacy, tolerability issues, etc.), or response consistency (e.g., lack of response in at least 3/5 attacks despite taking the medication early in the headache phase) [36]. The evidence gathered from this comprehensive literature search suggests that patients showing insufficient response/tolerability to one triptan based on any of these definitions could benefit from increasing the dose of the same triptan, switching to a different formulation of the same triptan (e.g., rapid release to subcutaneous), adding an NSAID to a triptan, or switching to another triptan [36].
To consolidate the variability and establish a consensus on what constitutes triptan treatment failure, the EHF has defined an “effective treatment (that applies to all acute therapies) of a migraine attack,” which forms the basis for objectively assessing triptan failure (see Fig. 6) [37].
![figure 6](http://media.springernature.com/lw685/springer-static/image/art%3A10.1007%2Fs40120-023-00576-4/MediaObjects/40120_2023_576_Fig6_HTML.png)
Adapted from Sacco S, Lampl C, Amin FM, et al. European Headache Federation (EHF) consensus on the definition of effective treatment of a migraine attack and of triptan failure. J Headache Pain. 2022;23(1):133. 2021;61(7):1021–1039
EHF consensus on the definition of effective treatment of a migraine attack, triptan responder, and triptan failure. *Contraindications may vary across countries and drugs. They can include coronary artery disease or angina, peripheral artery disease, stroke or TIA, and severe renal and hepatic insufficiency.
Expert Statement 6
In individuals with migraine with inadequate response to two triptans, or for those with cardiovascular risk factors, gepants/ditans can be considered as a reasonable alternative option.
The 60–70% response rates seen with triptans suggest that a majority of the patients would respond to first-line triptan therapy. Data showing that the gepants and ditans are superior to triptans are lacking. Moreover, given their prohibitive cost, the task force believes using gepants and ditans would be justified only in patients failing to respond to at least two triptans or those with pre-existing cardiovascular risk factors that would preclude using triptans. All physicians, especially GPs, who are usually the first to prescribe triptans, should adequately educate patients on triptan use and emphasize taking the medications early during an attack. Training physicians on these nuances of patient education can help improve adherence and response to triptan treatment. Gepants and ditans may be considered, preferably with a neurological consultation, if a sufficient trial with two triptans does not provide optimal relief to patients.
The expert panel agreed that the gepants and ditans could be reserved for those who show an inadequate response to two triptans or those in whom triptans are contraindicated (see Fig. 2).
Can Gepants, When Used for Acute Migraine Therapy, Be Combined with Preventive CGRP-Based treatments?
The neuropeptide CGRP is a crucial component of the migraine pathophysiology involved in peripheral and central sensitization. The serum CGRP levels are elevated during migraine attacks [38]. The discovery of CGRP has paved the way for several novel acute and preventive migraine therapies that intercept its pathway by binding to the CGRP peptide or its receptor. Both the gepants and the preventive anti-CGRP mABs work via the CGRP pathway (see Fig. 7) and have been approved either as abortive or preventive therapies.
![figure 7](http://media.springernature.com/lw685/springer-static/image/art%3A10.1007%2Fs40120-023-00576-4/MediaObjects/40120_2023_576_Fig7_HTML.png)
Source of figure: https://healthmatch.io/blog/guide-to-the-newest-fda-approved-medications-for-migraine
Mechanism of action of the gepants and CGRP-receptor and peptide antibodies.
Preventive migraine therapies help reduce the frequency and severity of migraine attacks but may not eliminate them entirely. Therefore, it is essential to include a strategy for managing breakthrough attacks in patients’ treatment plans.
Although CGRP-based therapies represent a significant milestone in migraine management, they are relatively new, and there is still much to be understood about them. The clinical implications, in terms of safety and efficacy, of using gepants as abortive therapies in patients who are taking prophylactic anti-CGRP mABs are still not entirely clear.
Combining gepants with the mABs, galcanezumab, fremanezumab, and eptinezumab, would result in CGRP antagonism via two different pathways, the downstream effects of which are not yet known. Combining gepants with erenumab would result in a dual blockade of CGRP receptors [38]. It is unclear if this dual blockade would be synergistic and lead to a more comprehensive inhibition of CGRP signaling and, thus, more effective migraine relief or if it would increase the risk of potential adverse events.
The limited evidence on using gepants for acute attacks combined with anti-CGRP mAB prophylaxis is preliminary but encouraging.
Jakate et al. have conducted a two-arm, multicenter, open-label, phase 1b randomized trial to evaluate the pharmacokinetic profile, safety, and tolerability of single-dose ubrogepant before or after the administration of a single dose of an anti-CGRP mAB (erenumab or galcanezumab). The pharmacokinetic parameters of ubrogepant were not significantly changed before and 4 days after the administration of the anti-CGRP mABs, implying a lack of pharmacokinetic drug–drug interaction between the gepants and anti-CGRP mABs, erenumab, and galcanezumab. Furthermore, the investigators did not observe any clinically significant alterations in the participants’ laboratory results, vital signs, and electrocardiogram (ECG) findings [39].
The ongoing COURAGE (COmbining UbRogepAnt and Preventives for MiGrainE) study is looking at the real-world effectiveness of ubrogepant in combination with either an anti-CGRP mAB or onabotulinumtoxinA or both. While the final results of this study are awaited, the interim findings presented at the 63rd Annual AHS meeting show that in patients taking anti-CGRP mAB prophylaxis, ubrogepant was effective in providing meaningful pain relief (MPR) 2 and 4 h after administration [40].
Freitag et al. also presented the results of their open-label, longitudinal study evaluating the combined use of gepants and anti-CGRP mABs. Their preliminary findings report no increase in adverse events with the combined use of gepants and anti-CGRP mABs [41].
The data from the studies conducted so far suggest that using gepants to provide relief during acute migraine attacks in patients taking anti-CGRP preventive therapy may not significantly elevate the risk of side effects relative to using these therapies individually. However, long-term studies to confirm the safety and efficacy of this combination are warranted. In the meantime, the decision to combine these therapies should be made on a case-by-case basis after considering the medical history, the severity and frequency of migraines, and the response to previous treatments. In this context, it is also crucial to acknowledge the risk of polypharmacy, which is high in the elderly as well as young patients with primary headache disorders [42]. Thus, a careful and individualized approach is essential to mitigate the risks associated with polypharmacy and ensure the risk-to-benefit ratio favors the concomitant use of gepants, preventive CGRP-based treatments, and in some cases additional medications that might be required to manage MBS like nausea.
Physician confidence in prescribing these combinations will improve as more real-world evidence accrues.
Expert Statement 7
The data on the safety of combining gepants when used for acute migraine therapy with CGRP-based therapies is limited to class lV studies. However, we believe this combination is probably safe and may be considered.
Despite the absence of the strongest level of evidence, the task force believes that the combination of gepants for acute attacks and preventive CGRP-based therapies may be a viable option in a select subgroup of patients. Clinical guidelines and recommendations on using these combinations will likely evolve as more robust long-term safety and efficacy data become available.
Although none of the expert panel members disagreed with this statement, their votes were split between “moderately agreed” and “strongly agreed,” with about 42% voting for “agreed.” Also, one panel member only “mildly agreed,” and one expressed a neutral opinion (see Fig. 2).
Acute Migraine Treatments in Special Populations: Pregnant Women and Children
Acute migraine treatments in special populations, such as children and pregnant women, require careful consideration and customization because of their unique healthcare needs and potential safety concerns.
Multiple observational studies show that migraine attacks can vary in pattern during pregnancy or, in some cases, improve or even resolve. For example, women who usually experience migraines without aura can start experiencing migraines with aura or vice versa. A systematic review of studies published over 20 years by Negro et al. found that about 50–75% of women observe a significant improvement, if not a complete resolution, in the frequency or severity of their attacks over the course of their pregnancy [43]. While some studies have observed a progressive improvement in symptoms from the first trimester, others found the symptoms to improve in the third trimester [43]. HEAD-HUNT, a large Norwegian study, evaluated the responses of 27,700 women to a headache questionnaire. The investigators found that migraine and non-migraine headaches were less prevalent in nulliparous pregnant women than in non-pregnant and nulliparous non-pregnant women. Also, headache was less prevalent in the third trimester but not in the first and second trimesters [44].
The relationship between breastfeeding and its protective effect against migraines remains uncertain. Moreover, sleep deprivation and stress post-delivery can trigger migraine attacks. Thus, migraines recur in the post-partum period, usually in more than 50% of the women who experience improvement during pregnancy [45].
Furthermore, the effects of pregnancy and breastfeeding on migraines vary from woman to woman, underscoring the importance of tailoring the treatment to fit the patient’s requirements and the stage of pregnancy without compromising the safety of the mother and the fetus or the baby.
Non-pharmacological approaches are the first line of treatment in pregnant and breastfeeding patients. Paracetamol is usually the first pharmacological treatment of choice during pregnancy and might suffice to provide relief during mild to moderate attacks. NSAIDs and triptans may also be considered on a case-by-case basis after ensuring that the benefits of migraine relief outweigh any potential treatment-related risk (see Fig. 8) [45].
![figure 8](http://media.springernature.com/lw685/springer-static/image/art%3A10.1007%2Fs40120-023-00576-4/MediaObjects/40120_2023_576_Fig8_HTML.png)
Adapted from Amundsen S, Nordeng H, Nezvalová-Henriksen K, Stovner LJ, Spigset O. Pharmacological treatment of migraine during pregnancy and breastfeeding. Nat Rev Neurol. 2015;11(4):209–219
Migraine treatments during pregnancy and lactation: Safety data based on the review of literature by Amundsen et al. Overview of the safety of commonly used antimigraine medications related to stage of pregnancy and lactation. Dark green circles indicate drugs that are considered safe. Light blue circles indicate drugs that are generally considered safe, but uncertainty exists owing to, for example, risks associated with specific drugs in a class or with a certain time period during pregnancy, or because of the limited data. Yellow circles indicate drugs for which increased risk of harm cannot be excluded, either because of studies revealing harmful effects or a lack of data supporting safety. Red circle indicates contraindicated drugs, for which the risk to the fetus or infant exceeds the therapeutic benefit to the mother. *Classification presupposes occasional use; risks may increase with frequent or excessive use.
The prevalence of migraine in children ranges between 3% and 10%, and an onset in adolescence likely suggests migraine will continue into adulthood [46]. Accurate diagnosis and treatment of migraine in children and adolescents are crucial for improving their overall QoL [47]. However, a lack of clinical studies on acute and prophylactic migraine treatments in pediatric patients is a significant roadblock. Physicians must depend on limited evidence-based treatment options to treat acute attacks in pediatric patients. Treatment must be selected after a thorough assessment of its risks versus benefits to ensure adequate relief to the patients while avoiding exposure to adverse events. In some cases, the risk of unmanaged migraine symptoms may outweigh potential treatment-related risks.
The practice guidelines for the acute treatment of migraine in children and adolescents jointly drafted by the AAN and AHS emphasize treating early, identifying and modifying lifestyle factors likely to trigger attacks, choosing the best-suited treatment delivery route (non-oral vs. oral), and avoiding medication overuse. Children and adolescents have been observed to show an age-dependent exaggerated placebo effect, complicating the interpretation of treatment outcomes in clinical trials; this factor must be considered while choosing treatment [47,48,49].
The practice guidelines by the AAN and AHS recommend initially treating acute migraine attacks in children and adolescents with a non-prescription oral analgesic like ibuprofen. The triptans FDA-approved for use in children include almotriptan oral tablet (≥ 12 years), rizatriptan (6–17 years) oral dissolving tablet, sumatriptan/naproxen oral tablet (≥ 12 years), and zolmitriptan nasal spray (≥ 12 years) [44, 50]. There is moderate-grade evidence supporting the efficacy of nasal sumatriptan in reducing pain at 2 h in 12–17-year-old children with persisting headache. The level of evidence available for the oral formulations of almotriptan, rizatriptan, and zolmitriptan is either low or very low grade (see Fig. 9) [46].
Data on the safety and efficacy of gepants and lasmiditan in pregnant women and the pediatric population are unavailable.
Expert Statement 8
We suggest exercising caution in prescribing any medication to treat acute migraine attacks in pregnant women. However, the use of sumatriptan can be considered during pregnancy. Risks/benefits need to be assessed individually. On the other hand, there is insufficient data to recommend the use of gepants/ditans during pregnancy. We also do not recommend the use of ditans/gepants for patients less than 18 years of age, while some triptans can be considered for patients aged 12–17 years.
The task force believes an emphasis on exercising caution when prescribing all treatments for acute migraine attacks constitutes a responsible and patient-centered approach. Sumatriptan may be considered in cases where the benefits of treating acute attacks outweigh the treatment-associated risks. Approved triptans may also be an option in treating acute attacks in pediatric patients with migraine. As gepants and ditans are relatively new treatments, their safety and efficacy in pregnant women and children are not yet well established.
The expert panel’s agreement with the approach recommended by the task force for pregnant women and children suggests that it is the most well-suited strategy for these special populations (see Fig. 2).
Optimal Management of Patients’ Most Bothersome Symptoms
The primary symptoms used to diagnose migraine include pain, nausea, photophobia, and phonophobia. The most bothersome symptom is the symptom of a migraine attack, apart from pain, that is the most distressing to an individual patient.
The guidance issued by the FDA in February 2018 for developing drugs for acute treatment of migraine represented a shift in the approach to evaluating migraine treatments. Instead of focusing on the four co-primary endpoints (relief from pain, nausea, photophobia, and phonophobia) clinical trial protocols used previously, the guidance now recommends using only two co-primary endpoints—freedom from pain and freedom from MBS 2 h after treatment administration [51]. Before this guidance incorporating the MBS concept was issued, clinical trials evaluating acute migraine therapies, including triptans, required demonstration of treatment efficacy in relieving symptoms that were sometimes not present in patients at baseline, i.e., before treatment. To overcome this challenge and make meaningful interpretations possible, clinical trials conducted earlier required larger sample sizes. Although these clinical trials have established the efficacy of triptans in treating acute migraine attacks, extrapolating their findings in the current clinical context of MBS is challenging.
Moreover, the introduction of MBS in more recent trials, such as those on gepants and ditans, has lowered the sample size requirements and allowed assessment of treatment efficacy that is clinically more relevant from a patient’s perspective. Applying the findings of these studies to real-world clinical practices while treating patients’ MBS is relatively straightforward.
The impact of various acute therapies on non-pain migraine symptoms, i.e., nausea, vomiting, photophobia, and phonophobia, can vary from person to person. Moreover, nausea and vomiting associated with migraine are distressing and can cause patients to delay taking oral drugs and hinder their absorption, adversely impacting therapeutic efficacy. As oral medications depend on efficient gastric emptying and gastrointestinal absorption, migraine-induced gastroparesis can cause inconsistent efficacy or even render these therapies ineffective [52].
Thus, in the presence of nausea and vomiting, the route of drug administration is an essential factor to consider. Tailoring treatment to address the specific characteristics of the migraine, which include not only the headache but also the other bothersome symptoms, is crucial for achieving patient satisfaction with adherence to treatment, and improving clinical outcomes.
Clinical trials evaluating the effects of ubrogepant and rimegepant on MBS have shown favorable results, with greater rates of patients in the active treatment cohorts experiencing freedom from MBS at 2 h than those in the placebo treatment cohorts [32, 33]. Integrated analyses of two phase 3 clinical trials on lasmiditan (SPARTAN and SAMURAI) showed significantly higher rates of freedom from MBS starting as early as 30 min in the lasmiditan-treated group compared to the placebo-treated group (lasmiditan 100 mg, 11.1%, p = 0.015; lasmiditan 200 mg, 13%, p < 0.001; placebo, 7.9%) [53].
A patient-centered migraine management strategy that considers the complete clinical picture, patient preferences and needs, and treatment safety, tolerability, and affordability is likely to be the most effective.
Expert Statement 9
Triptans can be tried to manage MBS on a case-by-case basis. Antiemetics should be considered in all individuals who are troubled with nausea or vomiting. On the other hand, we suggest that lasmiditan, rimegepant, and ubrogepant can be considered reasonable options for managing MBS.
Given the established track record of triptans in treating acute migraine attacks, the task force believes HCPs must assess patients’ specific migraine characteristics, medical history, and individual responses to treatment to determine whether triptans are an appropriate choice. Addressing nausea and vomiting is crucial as it can improve patients’ overall comfort, allowing them to tolerate oral therapies better. As gepants and lasmiditan have been specifically evaluated for treating patients’ MBS, they may be reasonably considered on a case-by-case basis. Providing patients with the most effective and well-tolerated treatment for their unique migraine symptoms can positively impact their overall QoL.
While most of the expert panel (95.8%) agreed/strongly agreed/mildly agreed with this statement, one panelist (4.2%) mildly disagreed because of the inclusion of lasmiditan in this statement. However, on the basis of the predefined criteria, this statement was adopted as a consensus statement (see Fig. 2).
Discussion
Healthcare practices and infrastructure, access to resources, drug regulations, cultural norms, and patient needs and preferences vary from among countries. These factors influence healthcare delivery and the patient journey. The expert panel comprising experienced neurologists from the UAE recognized the need to establish UAE-specific consensus statements that consider these unique cultural and demographic factors and provide evidence-based guidance on the acute treatment of migraine. The objective was to cover the entire spectrum of acute migraine treatment, including what goals to set, when to treat during an acute attack, strategies to use in general and special populations (i.e., pediatric and pregnant patients), and how to manage MBS.
Identifying treatment goals that would provide physicians with a clear framework for assessing patients’ responses and serve as a roadmap for developing comprehensive treatment plans was the next logical step in developing these consensus statements. The expert panel agreed that the acute treatment goals set by the AHS in its 2021 updated consensus statement align well with the physicians and patients from the UAE and can be adopted.
The timing of drug administration during an acute attack impacts effectiveness, as has been demonstrated by several prospective and retrospective studies on almotriptan, sumatriptan, zolmitriptan, eletriptan, and rizatriptan—early administration of treatment, when the pain intensity was still mild, resulted in better outcomes in all these studies [19, 20, 54,55,56,57]. On the basis of these findings, and in line with the EHF/EAN and AHS consensus statements, the expert panel concurred that early intervention during an acute attack can maximize the effectiveness of administered therapies and reduce disability associated with more severe attacks.
Although overall treatment goals are similar between the EHF and AHS consensus statements, the strategies they recommend to achieve them differ slightly. The EHF/EAN consensus statement recommends a stepped-up care approach in which physicians start with simple or combination analgesics, which are relatively inexpensive, while reserving the more expensive and migraine-specific therapies for those who do not respond to the initial lines of treatment. This method helps to minimize treatment side effects. On the other hand, the stratified care approach, recommended by the AHS, involves matching patients’ symptom severity with the intervention—less intensive treatment for mild symptoms and more intensive treatment for moderate to severe grade symptoms. This strategy reduces the trial and error in treatment selection. Although both strategies have advantages and disadvantages and are well founded in different clinical contexts, the panel unanimously agreed that the stratified care approach best suits the UAE healthcare system and patient population characteristics and should be adopted.
The concept of MBS has evolved after the FDA guidance was issued in 2018, suggesting that clinical trials for acute migraine treatments use pain freedom and freedom from the patient-identified MBS as co-primary endpoints [51]. Gepants and lasmiditan have demonstrated efficacy in addressing not only pain but also other migraine-associated symptoms in clinical trials [32, 33, 35, 58,59,60,61]. However, they are relatively new classes of migraine therapies with limited long-term and real-world data. Triptans, on the other hand, have been available for many years and are well established as a standard of care for migraine treatment but have not been specifically evaluated in the context of MBS. The absence of head-to-head clinical trials comparing the efficacy of these therapies in providing relief from MBS makes it challenging to place them in the treatment algorithm. Thus, it is difficult to choose between newer therapies (gepants and lasmiditan) that have been proven effective in managing MBS in RCTs but have a less established long-term track record, and well-established treatments like triptans that have not been evaluated for efficacy in managing MBS. Treatment choice relies on patients’ clinical profiles, including the nature and severity of their MBS, comorbidities, and medical history. Additionally, the affordability and availability of treatments are also crucial deciding factors. The EHF/EAN and AHS consensus statements do not specifically address the management of MBS [11, 12]. Managing MBS, however, cannot be overlooked as it is essential to improving patient QoL and functional ability. The proposed consensus statements suggest personalized treatment with triptans and antiemetics while also considering the availability of newer treatment options like ubrogepant, rimegepant, and lasmiditan for those who may benefit from alternatives to triptan.
Although these consensus statements provide a foundational framework to guide the treatment of acute migraine attacks, they are not exhaustive. They should be adapted and supplemented on the basis of patients’ needs and physicians’ clinical judgments. Moreover, they must be regularly reviewed and updated to reflect new developments in acute migraine treatments and the accumulation of local data. The availability of region-specific data can ensure that future updates of these consensus statements are more relevant from a UAE perspective. A lack of robust regional data on migraine prevalence, treatment practices, and outcomes poses significant challenges when developing regional guidelines for migraine management. We hope these consensus statements provide an impetus to generate region-specific data to help fill this knowledge gap. Establishing a UAE migraine registry can be a valuable source of real-world data collection in this respect.
Improving physician awareness about the latest research and drug approvals is crucial for delivering up-to-date care and making informed treatment decisions. Likewise, educating patients about different phases of migraine, potential triggers, lifestyle changes that can make a difference, treatment options and outcomes, and appropriate use of medications, including early intervention during an attack, can encourage them to play an active role in treatment decisions. Steps to improve physician awareness and patient education can facilitate the implementation of the proposed consensus statements.
The consensus statements support patient-centered care and have been developed through the collaboration of experienced specialists in the UAE. Thus, they can serve as an invaluable resource for the UAE government authorities to formulate regulations that ensure expensive therapies like gepants and ditans are accessible to those who need them while maintaining the sustainability of the UAE healthcare system. Although these consensus statements are developed primarily for the UAE, they have broad relevance and applicability as they are based on established international consensus statements and are backed by robust evidence.
Conclusion
Effective treatment of episodic migraine calls for a comprehensive and multifaceted approach that considers the complexity and individual variability in acute attacks and involves the use of abortive non-specific and migraine-specific therapies, lifestyle modifications, and patient education.
The UAE’s healthcare system is a mix of public and private sectors, and its migraine patient population is culturally diverse with a large expatriate component. Understanding these unique cultural norms and demographic factors is essential for HCPs to deliver patient-centered and culturally sensitive care to patients with migraine.
These UAE-centric consensus statements can help HCPs make informed decisions and offer standardized care to manage acute migraine attacks in the UAE patient population optimally. Their implementation will require interdisciplinary collaboration among healthcare professionals, including neurologists, GPs, nurses, and pharmacists.
Data Availability
Data sharing is not applicable to this article as no datasets were generated or analyzed during the current study.
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Medical writing support was provided by Dr. Preeti Nerurkar of Medcytes, Dubai, UAE, and funded by AbbVie Biopharmaceuticals GmbH, Dubai, UAE. Springer Healthcare is not responsible for the validity of the guidelines it publishes.
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All authors including Taoufik Alsaadi, Deeb M Kayed, Abubaker Al-Madani, Ali Mohamed Hassan, Derk Krieger, Naji Riachi, Pournamy Sarathchandran, and Suhail Al-Rukn discussed the results and contributed to the development of the final manuscript.
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Abubaker Al-Madani, Derk Krieger, Suhail Al-Rukn, and Ali Mohamed Hassan have received speaker and consultancy fees from Pfizer, Eli Lilly, Novartis, Lundbeck, and Abbvie. Taoufik Alsaadi and Naji Riachi have received research grants, as well as speaker and consultancy fees from Pfizer, Eli Lilly, Novartis, Lundbeck, and Abbvie. Deeb M. Kayed has received honoraria, travel support, speaker fees, and advisory board fees from Abbvie, Eli Lilly, Lundbeck, Novartis, and Pfizer. Pournamy Sarathchandran has no competing interest to declare.
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This article is based on previously conducted studies and does not contain any new studies with human participants or animals performed by any of the authors. The study received IRB approval from the American Center for Psychiatry and Neurology’s IRB ethical exemption, with the reference ACPN_IRB_0058. All experts were authors in the study.
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Alsaadi, T., Kayed, D.M., Al-Madani, A. et al. Acute Treatment of Migraine: Expert Consensus Statements from the United Arab Emirates (UAE). Neurol Ther 13, 257–281 (2024). https://doi.org/10.1007/s40120-023-00576-4
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DOI: https://doi.org/10.1007/s40120-023-00576-4