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. 2025 Dec 18;15(1):15–28. doi: 10.1007/s40120-025-00874-z

Moderate to Severe Acute Migraine Attacks: An Opinion Paper on the Use of Triptans and Triptan-NSAIDs Combinations in Individualized Treatment Plans

Peter J Goadsby 1,2,✉, Alexandra J Sinclair 3,4, Shazia K Afridi 5, Christian Lucas 6, Jerôme Mawet 7, Michel Lanteri-Minet 8,9, Xavier Moisset 10, Hans Christoph Diener 11, Charly Gaul 12,13, Tim Patrick Jürgens 14,15, Marja-Liisa Sumelahti 16, Margarita Sanchez del Rio 17, Patricia del Pozo-Rosich 18, Antonio Russo 19, Piero Barbanti 20,21
PMCID: PMC12804549  PMID: 41410843

Abstract

This opinion paper on the acute treatment of migraine addresses the definition and recognition of acute migraine attacks, highlighting the variety of symptoms and manifestations. It describes the available treatments and guidelines, noting significant country-specific variations. The paper also discusses the prescribers’ knowledge and updates, recognizing the segment-specific differences. Despite nonsteroidal anti-inflammatory drugs (NSAIDs) and triptans being universally recommended as first-line treatments, their visibility in the field has diminished due to the promotion of newer medicines. The authors, a panel of 15 experts from six European countries, emphasize the underutilization of triptans and advocate for their prescription, and also their use in combination with NSAIDs, when NSAIDs alone are not sufficiently effective. The panel specifically considered the sumatriptan succinate–naproxen sodium combination, which was recently introduced in Europe and may be beneficial in patients not responding to NSAIDs, particularly for special patient groups, such as those with menstrual-related acute migraine or migraine attacks with prolonged pain or postdrome. Finally, the consensus highlights the need for individualized treatment plans and the importance of considering patient preferences and specific symptoms, integrating evidence-based recommendations with patient-centered care to optimize migraine management.

Graphical Abstract

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Keywords: Migraine individualized treatment, Menstrual-related migraine, Sumatriptan–naproxen combination

Key Summary Points

Underutilization of triptans in clinical practice: Triptans are underutilized due to a focus on newer therapies and prescriber hesitancy. Bridging the knowledge gap, particularly among general practitioners, would ensure that patients receive optimal treatment.
Triptans and triptan–NSAID combinations as first-line treatments: Triptans, alone or in combination with nonsteroidal anti-inflammatory drugs (NSAIDs), remain the gold standard for moderate to severe acute migraine attacks.
Efficacy of sumatriptan–naproxen combination: The fixed-dose combination of sumatriptan and naproxen targets multiple mechanisms of migraine pathophysiology, providing rapid and sustained relief.
Special patient groups and clinical nuances: The sumatriptan–naproxen combination is particularly advantageous for specific patient groups, such as those with menstrual-related migraines, prolonged attacks lasting over 6 h, and longer postdromes.
Patient-centered, individualized treatment plans: This opinion paper emphasizes the importance of tailoring migraine treatment to individual patient needs and preferences.
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Digital Features

This article is published with digital features, including an infographic, to facilitate understanding of the article. To view digital features for this article, go to 10.6084/m9.figshare.30724811.

Current Practice

Acute Migraine Attacks: A Variety of Symptoms and Manifestations Leading to a Quality-of-Life Reduction and Economic Burden

Migraine is a prevalent and debilitating neurological disorder that might severely impact patients’ quality of life and imposes a substantial economic burden on society [1]. Affecting approximately 12–15% of the global population, migraine is characterized by recurrent episodes of severe headache, often accompanied by nausea, sensitivity to light and sound [2, 3], and in some cases also by vomiting. Without appropriate treatment, attacks can last from 4 to 72 h, rendering many sufferers unable to perform daily activities, including work and social engagements. Most people living with migraine have a premonitory (prodromal) and a postdromal phase that extends this period of disability [4, 5].

The personal impact of migraine is profound. Patients often experience a reduced ability to function during migraine attacks, leading to missed workdays and decreased productivity [6]. In a population survey, over one-third of physician-diagnosed migraine patients reported having missed at least one workday, 80.1% had missed at least 1 day of household work, and 64.9% missed at least 1 day of family or social activity in the previous 3 months [7]. This level of disability not only affects the individual but also places a strain on their families, who may need to provide additional support and care during migraine episodes [7]. The chronic nature of migraine can lead to long-term psychological effects, including anxiety and depression, further diminishing the quality of life for sufferers and their families. The stigma of migraine is substantial in society and explains a need for increased advocacy and awareness [8, 9].

Economically, migraine represents a relevant burden on society, remaining second among the world’s causes of disability and first among disability in young women [10]. The annual direct healthcare costs for patients with migraine in the United States are estimated at $22,364 per person, with indirect costs, such as lost productivity, amounting to over $19 billion [11]. These costs are not limited to the United States [12]; similar economic impacts are observed globally. For instance, in the European Union, the annual cost of migraines is estimated at €111 billion, with direct costs per person averaging €1222 [13]. These figures highlight the extensive socioeconomic impact of migraines, which includes healthcare expenses, lost workdays, and reduced productivity [14].

Effective management and treatment strategies are crucial in reducing this burden. Increased awareness, better access to healthcare, and advancements in migraine-specific treatments can help alleviate the personal and economic impact of this debilitating condition. Addressing these issues requires a concerted effort from healthcare providers, policymakers, and society to ensure that migraine sufferers receive the support and treatment they need.

Acute Migraine Treatments: What are the Options?

Acute treatments can be broadly categorized into nonspecific analgesics, nonsteroidal anti-inflammatory drugs (NSAIDs), triptans, other substances (caffeine, antiemetics), combination therapies of the aforementioned, and newer agents such as gepants and ditans [15]. The availability and preference for these treatments vary significantly between countries due to factors such as regulatory approvals and healthcare policies, which incorporate and reflect wider economic considerations and influences, and local clinical practices. Effective acute treatment potentially also has long-term benefits for the patient: an association between ineffective acute treatment and progression to chronic migraine has been reported [16, 17].

Nonspecific Analgesics and NSAIDs

Nonspecific analgesics like paracetamol (acetaminophen) and NSAIDs such as ibuprofen, naproxen, diclofenac, and aspirin are commonly recommended as first-line treatments for mild to moderate migraine attacks (Fig. 1) [15, 18]. In most countries, these drugs will be available over the counter without reimbursement.

Fig. 1.

Fig. 1

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Acute treatment of migraine in adults.

Adapted from the European Headache Federation and World Health Organization (WHO) [54], European expert consensus [24], and National Institute for Care and Excellence guidelines [59]

Triptans

Triptans are considered the first-line treatment for moderate to severe migraine attacks. They are serotonin, 5-HT1B/1D receptor agonists that produce peripheral and central effects such as reduction of neuropeptide release and trigeminal neuronal inhibition [19]. The role of vasoconstricting pleiotropic effects by triptans is still under discussion [20]. Available triptans include sumatriptan, almotriptan, eletriptan, frovatriptan, naratriptan, rizatriptan, and zolmitriptan, although not every country has all of them. Guidelines recommend triptans for their efficacy in achieving pain relief and reducing associated symptoms like nausea and photophobia; the International Headache Society and European Headache Federation advocate the use of triptans early in an attack for optimal results [15, 18]. While triptans are generally available as mono-dose oral treatment, some are also available in different doses and different formulations (as nasal spray or subcutaneous injections) but this picture is highly dependent upon the various countries and territories.

Combination Therapies

Three types of combinations with NSAIDs are available commercially and are used in clinical practice: (a) in combination with an analgesic (aspirin and paracetamol), (b) with a triptan, and (c) with other substances (caffeine, metoclopramide).

Combination NSAID/triptan therapies are recommended for patients who do not achieve sufficient relief with NSAID or triptan alone. Combining a triptan with an NSAID can enhance efficacy compared with monotherapy by targeting multiple mechanisms involved in migraine pathophysiology [21]. While limited data exist for other combinations (e.g., rizatriptan plus rofecoxib or almotriptan plus aceclofenac), the fixed-dose combination of sumatriptan and naproxen sodium is particularly noted for its performance in achieving sustained pain relief and reducing recurrence rates and is guideline-endorsed for patients with moderate to severe attacks [18, 22, 23].

Gepants and Ditans

Gepants (calcitonin gene-related peptide [CGRP] receptor antagonists) and ditans (5-HT1F receptor agonists) are newer classes of migraine-specific medications that offer alternatives for patients who cannot use triptans due to inefficacy, poor tolerability, or cardiovascular contraindications such as serious vascular conditions. The higher cost of both these classes of agents compared with NSAIDs and triptans often constrain their availability, however, which relegates them to third-line options in some jurisdictions [15, 24].

Other Options

Among non-specific pharmacological treatments, it is important to highlight the role of antiemetics in migraine, as several agents—particularly metoclopramide—have been shown to be effective for acute migraine relief [25]. Another option is the use of noninvasive neuromodulation devices [26, 27], which may be especially beneficial for patients who experience insufficient efficacy, adverse effects, or contraindications to pharmacological treatments. Results are particularly promising for remote electrical neuromodulation [28].

Regional Variations

The availability of migraine treatments varies significantly across different countries and can lead to the deployment of medications running ahead of expert opinion. The American Headache Society recognizes the importance of individualizing treatment and considering the options available [29].

The Prescribers: Variability in Knowledge and Updates Between GPs and Specialized Neurologists

General practitioners (GPs) and specialized neurologists differ significantly in their knowledge and updates regarding the diagnosis and treatment of migraine patients (see recent survey on migraine management in France as an example [30]). In general, GPs might have had limited training in the management of headache disorders; thus they may not be as adept at distinguishing between different types of headache disorders and may be less familiar with the nuances of migraine subtypes, such as migraine with aura or chronic migraine. Their approach may be conservative, focusing on widely accepted and well-established medications, such as NSAIDs.

Specialized neurologists, on the other hand, can be expected to have in-depth knowledge of the pathophysiology, diagnostic criteria, and treatment options for migraine, to be skilled in differentiating between various headache disorders and subtypes of migraine, and to be more likely to recognize and diagnose complex cases, such as hemiplegic migraine or migraine with brainstem aura. They are more likely to be conversant in the latest research, clinical trials, and guidelines and to incorporate new evidence-based practices into their treatment protocols, including the use of combination treatments such as sumatriptan–naproxen sodium as part of an individualized approach to treatment. In addition, their advanced expertise and awareness make them keener to prescribe newer, costly therapies, which in many countries they alone may be permitted to prescribe. For completeness, it should be mentioned that in some countries such as Germany, pain specialists (mostly non-neurologists such as anaesthesiologists) treat patients with headache as well.

The differences between GPs and specialists in diagnosing and treating migraine highlight the importance of specialized knowledge and continuous education. While GPs play a crucial role in initial diagnosis and management, patients with complex or refractory migraines may benefit from referral to a specialist for more accurate diagnosis and access to a broader range of treatment options, potentially leading to better patient outcomes. Since specialist headache care will not be available for all migraine patients due to the high prevalence of the disease, substantial improvement can be made by encouraging GPs in offering the most effective therapies available.

Cooperation between neurologists and GPs in the collection of real-world data on migraine epidemiology has been successfully tested, for example, suggesting that GPs may be overestimating the number of cases of migraine with aura in their patient population [31].

Methods

DELPHI Structured Communication Technique

This manuscript describes the element of consensus obtained after all authors answered an anonymized single-round Delphi questionnaire, followed by an open discussion on the results. The results of the discussion were used as the base for the present manuscript, which was then independently corrected by all participants.

Expert Opinion

STATEMENT: Triptans, Alone or in Combination with NSAIDs, are Advocated as First-Line Treatment When NSAIDs Alone are Not Sufficiently Effective

NSAIDs are effective in mild to moderate migraine attacks, while triptans are preferred for moderate to severe episodes. Despite their established role, however, these medications may receive less focus in clinical practice, due to the promotion of newer and more expensive drugs like gepants and ditans.

Evidence from clinical trials has established that NSAIDs and triptans can be highly effective for many patients. Moreover, triptans have broadly comparable response rates to gepants [32–34] and, in some meta-analyses, appeared even more effective than gepants and ditans [35, 36], although there are important methodological issues with the more recent meta-analyses [37]. Unquestionably, the availability of gepants has added an important tool to options for management of migraine, since triptans are not appropriate for all patients. Specifically, head-to-head studies of triptans and gepants have been performed for telcagepant [34], rimegepant [32], and BI44370 TA [33], although the rimegepant study had an adaptive design.

As regards combinations of triptans and NSAIDs, the combination of sumatriptan and naproxen has demonstrated superior efficacy in achieving sustained pain relief compared to monotherapy with either sumatriptan or naproxen alone [21]. The proven efficacy, safety, and cost-effectiveness of NSAIDs and triptans therefore make them indispensable in the acute treatment of migraine. A balanced approach considering individual patient needs and the evidence base is essential for optimal migraine management.

One consideration in particular that may be used against the use of triptans is that they are contraindicated in patients with uncontrolled hypertension, coronary artery disease, and other cardiovascular conditions. Concern for potential adverse events may persist among prescribers and patients, even though studies and over 30 years of clinical experience have shown that triptans are generally safe and well-tolerated [38], even in patients with cardiovascular risk factors [39]. In fact, it is reported that “large observational studies have not shown an increased risk of acute coronary syndromes and ischemic strokes in patients who treat their migraine attacks with triptans” [39], and this and similar reassurances probably need to be more widely communicated to prescribers.

In their patient journeys, all migraineurs would have tried NSAIDs and were very likely to be unsatisfied when approaching a GP or a specialist. Since studies have shown that triptans are more effective than NSAIDs in achieving freedom from pain at 2 h and sustained pain relief at 24 h, triptans or triptan–NSAID combinations should be prescribed for acute migraine attacks when NSAIDs have proven insufficiently effective [15]. This approach ensures rapid and sustained relief, improving patient satisfaction and quality of life.

STATEMENT: Evidence-Based Medicine is Available for the Sumatriptan–Naproxen Combination as First-Line Treatment when Monotherapy is Not Sufficient

The combination of sumatriptan and naproxen has been studied extensively for the acute treatment of migraine, demonstrating significant efficacy and tolerability compared to monotherapy with either drug alone or placebo. A comprehensive survey and appraisal of experience with this product in clinical trials has recently been published [40]. Key findings may be summarized as follows.

Efficacy

Pain relief: Sumatriptan–naproxen combination consistently delivers better pain relief than placebo, sumatriptan alone, or naproxen alone, providing higher rates of pain-free response at 2 h and sustained pain-free response up to 24 h [21].

Associated symptoms: Sumatriptan–naproxen combination was more effective in reducing migraine-associated symptoms such as nausea, photophobia, and phonophobia. Studies by Lipton et al. and Silberstein et al. highlight the combination’s ability to alleviate both traditional migraine symptoms and non-traditional symptoms including neck pain and sinus discomfort [41, 42].

Consistency of Response

Multiple attacks: Sumatriptan–naproxen combination maintained efficacy across multiple migraine attacks, with consistent pain-free and sustained pain-free responses over four treated attacks [41].

Safety and Tolerability

Sumatriptan–naproxen combination is generally well-tolerated, with adverse events similar to those of the individual components. Common adverse events included nausea, dizziness, and muscle tightness, which were mild to moderate in severity. The incidence of adverse events does not increase with repeat dosing up to 12 months [43, 44].

Patient Satisfaction and Quality of Life

Functionality and productivity: Patients treated with the sumatriptan–naproxen combination experienced significant improvements in functionality, productivity, and overall satisfaction compared to placebo and monotherapy [7, 44]. The combination allowed more patients to return to normal functioning more quickly and reduced productivity loss.

Pharmacokinetics

Distinct profile: The sumatriptan–naproxen combination tablet has a distinctive pharmacokinetic profile, with rapid absorption and short half-life for sumatriptan, and slower absorption with a longer half-life for naproxen. This combination may underpin the clinical profile of rapid but sustained symptom relief [45].

STATEMENT: In Some Patient Groups, the Sumatriptan–Naproxen Combination Could be Particularly Advantageous as First-Line Treatment

The combination of sumatriptan and naproxen has been shown to be particularly beneficial for several specific patient groups. Salient data for each group are summarized below.

Menstrual-Related Migraine

The link between migraine and menstruation is well known, with estrogen playing a key role, resulting in approximately one in five female migraineurs having migraine in at least 50% of menstrual cycles [46, 47]. Menstrual migraine is often more severe and longer-lasting than non-menstrual migraine [48] according to the International Classification of Headache Disorders, Third Edition (ICHD-3) criteria, being further subdivided into pure menstrual migraine (PMM) and menstrual-associated migraine (MAM) [3].

  • o

    Efficacy: The sumatriptan–naproxen combination is effective in treating menstrual migraine, providing significant relief from both migraine pain and associated menstrual symptoms such as dysmenorrhea [48] [49–51].

  • o

    Relief of symptoms: The sumatriptan–naproxen combination has been shown to relieve non-pain-related menstrual symptoms like bloating, fatigue, and irritability, which are common in menstrual migraineurs [51].

  • o

    Sustained relief: The sumatriptan–naproxen combination offers sustained pain-free response up to 48 h, which is crucial for managing the prolonged nature of menstrual migraines [49].

Migraine Attack with Postdrome

The postdrome phase refers to the constellation of symptoms that follow the resolution of the migraine-related headache itself, including mood changes (irritability, depression, euphoria), food cravings, neck stiffness, fatigue, increased yawning, and cognitive changes (e.g. difficulty concentrating) [52].

Clinical benefits: Sumatriptan–naproxen may provide rapid and sustained relief, which can be beneficial in managing the lingering symptoms of postdrome, such as fatigue and cognitive impairment [42].

Migraine Attack with Prolonged Pain Over 6 Hours

Acute migraine with prolonged pain may involve nausea, vomiting, and sensitivity to light and sound, and physical activity may worsen symptoms. Recovery is slow, and the pain may fluctuate but never fully resolves without medical intervention.

Efficacy: The sumatriptan–naproxen combination has been shown to be effective in treating prolonged migraine attacks, providing both immediate and sustained relief [21, 41]. The combination reduces the likelihood of headache recurrence within 24 h, which is particularly important for patients experiencing long-lasting migraine attacks [52].

Other Groups

Patients who have previously reported poor response to triptan monotherapy may benefit from the sumatriptan–naproxen combination [53].

STATEMENT: Therapies Should Always be Prescribed in a Patient-Centered, Individualized Mode, Leaving the Patient to Choose the Best for Their Own Symptoms

Triptans, NSAIDs, and triptan–NSAID combinations (also in combination with antiemetics) should be prescribed in a patient-centered, individualized manner to optimize migraine management (Fig. 2). This approach involves tailoring treatment to the patient’s specific symptoms and preferences, potentially offering multiple prescriptions to allow the patient to select the option most effective for them.

Fig. 2.

Fig. 2

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Elements to be considered when planning an individualized treatment for acute migraine attacks

Presenting multiple triptans or triptan–NSAID combinations allows patients to experiment and identify the most effective treatment for their unique migraine patterns. This strategy acknowledges the variability in migraine presentations and the importance of patient autonomy in managing their condition [41, 54–57]. Ultimately, a patient-centered approach can improve treatment outcomes, satisfaction, and quality of life for individuals with migraine [58].

Limitations

This manuscript emphasizes the efficacy and safety of the combination sumatriptan–naproxen as the latest entry in the triptans–NSAIDs in Europe. The authors discussed and described this new entry and its role in the therapeutic palette, adding a new opinion among the many already published on other drug families. This paper is intended neither as a systematic review of all existing therapies for acute migraine pain nor as a guideline.

It is important to note that the data collected for the sumatriptan–naproxen combination predate the CGRP era. Therefore, some clinical judgment is needed to place those data in the context of current practice.

As regards the selection of a one-tier Delphi method, we chose the approach used to maximize the opinions gained from a large group of experts for whom repeated rounds of a Delphi process may have led to attrition in opinion.

Conclusions

This manuscript underscores the critical role of triptans and triptan–NSAID combinations as first-line treatments for moderate to severe acute migraine attacks not responding to NSAIDs alone, emphasizing their efficacy, safety, and cost-effectiveness. Despite the emergence of newer therapies like gepants and ditans, evidence supports the sustained pain relief and reduced recurrence rates offered by triptans and triptan–NSAID combinations. In this class, the sumatriptan–naproxen combination has shown consistent efficacy and may be considered favorably among the first-line options for the acute treatment of migraine, particularly for menstrual-related migraines and for prolonged migraine attacks. The nuanced discussion highlights the need for individualized, patient-centered treatment plans, empowering patients to determine the best options for their symptoms. Bridging gaps in prescriber knowledge, especially among general practitioners, and addressing cardiovascular safety concerns are pivotal for optimizing migraine management.

Acknowledgments

Medical Writing/Editorial Assistance

We thank Peter Hughes (HughesAssociated, Oxford, UK) for editing the text, Mrs. Shrestha Roy (Orion Pharma, Mumbai, India) for providing the graphic solutions, and Dr. Jan Erik Timmermann and Adj. Prof. Piero Pollesello (Orion Pharma, Espoo, Finland) for coordinating the collection of the answers to the Delphi questionnaire.

Author Contributions

Peter J. Goadsby sketched the manuscript based on the results of the Delphi exercise. All the other authors, Alexandra J. Sinclair, Shazia K Afridi, Christian Lucas, Jerôme Mawet, Michel Lanteri-Minet, Xavier Moisset, Hans Christoph Diener, Charly Gaul, Tim Patrick Jürgens, Marja-Liisa Sumelahti, Margarita Sanchez del Rio, Patricia del Pozo-Rosich, Antonio Russo, and Piero Barbanti, independently corrected the manuscript. Peter J. Goadsby finalized the text. The authors’ opinions are independent, and the text of the manuscript was not influenced by the sponsor.

Funding

The role of the sponsor, Orion Pharma (Espoo, Finland), was limited to the logistical support in the coordination of the Delphi exercise and in funding of the journal’s rapid service fee. Orion Pharma is the European distributor of a fixed combination of sumatriptan–naproxen (sumatriptan succinate and naproxen sodium), recently approved by the regulatory authorities in Europe.

Data Availability

Data sharing is not applicable to this article as no datasets were generated or analysed during the current study.

Declarations

Conflict of Interest

Apart from the honoraria related to the participation in the Delphi questionnaire, Peter J. Goadsby, Alexandra J. Sinclair, Shazia K Afridi, Christian Lucas, Jerôme Mawet, Michel Lanteri-Minet, Xavier Moisset, Hans Christoph Diener, Charly Gaul, Tim Patrick Jürgens, Marja-Liisa Sumelahti, Margarita Sanchez del Rio, Patricia del Pozo-Rosich, Antonio Russo, and Piero Barbanti have nothing relevant to declare regarding the publication of this paper.

Ethical Approval

The Delphi exercise was conducted by collecting answers from the co-authors, and not from patients or anonymous healthcare providers. It was a discussion technique aimed at reaching a consensus. No new data or studies were considered, just the co-author expertise and the existing literature, and for this reason, ethical approval was not needed.

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