Migraine is a debilitating neurological disorder that continues to pose a significant global health challenge. Characterised by recurrent episodes of moderate to severe headache lasting up to 72 hours, it affects over one billion people worldwide. Among women aged 15–49 years, migraine is the leading cause of disability, accentuating its widespread impact on both individual and societal levels. Beyond the immediate discomfort, migraine episodes often lead to reduced productivity, impaired personal welfare, and adverse socioeconomic outcomes. Understanding the most effective treatments for acute migraine is crucial for improving the quality of life for millions of sufferers worldwide.

The Burden of Migraine

The pervasive impact of migraine extends far beyond the physical symptoms. For many, migraines disrupt daily life, work productivity, and social engagement. This burden is especially pronounced among women in their reproductive years, who often juggle work and caregiving responsibilities alongside managing chronic pain. The economic implications are equally substantial, with migraine-related healthcare costs and lost productivity contributing to a significant financial toll on individuals and healthcare systems.

The urgency to address migraine effectively has led to the development of numerous treatments. These treatments aim to provide rapid relief from pain while minimising side effects and addressing the broader implications of the condition. Understanding the nuances of these treatments is essential for clinicians and patients alike.

Current Approaches to Acute Migraine Management

The acute management of migraine focuses on alleviating pain and restoring functionality as quickly as possible. International clinical guidelines recommend a stepwise approach to treatment, emphasising both efficacy and tolerability. Non-steroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen and diclofenac potassium, are commonly endorsed as first-line treatments due to their accessibility and general safety profile. However, for moderate to severe episodes or when NSAIDs prove ineffective, triptans are considered the gold standard.

Triptans, a class of selective serotonin (5-HT1B/1D) receptor agonists, have long been recognised for their effectiveness in managing acute migraine episodes. These drugs work by constricting blood vessels and inhibiting pain pathways in the brain. Despite their efficacy, triptans are underutilised, with usage rates ranging from 16.8% to 22.7% in the United States and 3.4% to 22.5% in Europe. Factors contributing to this underuse include contraindications for patients with cardiovascular conditions and concerns about side effects.

In recent years, newer treatments such as lasmiditan and gepants (e.g., rimegepant, ubrogepant) have emerged as alternatives, particularly for patients who cannot tolerate or are contraindicated for triptans. These drugs, which lack vasoconstrictive effects, offer new hope for individuals with cardiovascular risks. However, they come with their own set of limitations, including high costs and specific adverse effects.

Comparative Efficacy and Tolerability of Migraine Treatments

A recent systematic review and network meta-analysis of 137 double-blind randomised controlled trials, involving 89,445 participants, provides valuable insights into the comparative efficacy and tolerability of various migraine treatments. The study evaluated outcomes such as pain freedom within two hours, sustained efficacy, and adverse events, offering a comprehensive overview of available options.

Triptans: The analysis highlighted four triptans—eletriptan, rizatriptan, sumatriptan, and zolmitriptan, as the most effective options for acute migraine treatment. These drugs consistently outperformed other treatments in terms of rapid pain relief and sustained efficacy. Their balanced profiles of efficacy and tolerability make them ideal for managing acute migraine episodes.

Newer Drugs: Lasmiditan and gepants, while providing alternatives for patients with contraindications to triptans, showed mixed results. Lasmiditan was associated with side effects such as dizziness, paraesthesia, and sedation. Additionally, the FDA’s recommendation against driving for eight hours post-intake poses practical challenges for its use. Among the gepants, rimegepant demonstrated good tolerability, while ubrogepant was linked to an increased risk of nausea. These limitations, combined with the high costs of these medications, restrict their widespread adoption.

NSAIDs: Traditional treatments like NSAIDs exhibited variable efficacy. Diclofenac potassium showed efficacy and tolerability comparable to sumatriptan but with wide confidence intervals. Ibuprofen and acetylsalicylic acid demonstrated moderate efficacy but were less effective than triptans. NSAIDs remain a viable option for patients who prioritise safety over rapid pain relief.

Paracetamol: While paracetamol showed limited efficacy for achieving pain freedom within two hours, its favourable tolerability profile makes it a reasonable choice for patients seeking low-risk treatment options.

Barriers to Optimal Treatment

Despite the availability of effective treatments, several barriers hinder the optimal management of migraine. Chief among these is the underutilisation of triptans, largely due to concerns about cardiovascular safety and contraindications for patients with vascular diseases. However, emerging evidence suggests that these concerns may be overstated. Studies examining high-dose intravenous eletriptan or subcutaneous sumatriptan found no clinically significant vasoconstriction in patients undergoing diagnostic coronary angiography. Revisiting the cardiovascular safety of triptans could expand their use and improve treatment outcomes.

Cost also remains a significant barrier, particularly for newer drugs like lasmiditan and gepants. These treatments, while effective, are expensive and may not be covered by insurance in many regions. This financial hurdle limits access for many patients, especially those in low and middle-income countries. Including the most effective triptans in the World Health Organisation’s Model List of Essential Medicines (currently limited to sumatriptan) could help address this issue by promoting global accessibility and standardising care.

Implications for Clinical Practice

The findings of the systematic review and meta-analysis have important implications for clinical practice:

1. Triptans as First Choice: Eletriptan, rizatriptan, sumatriptan, and zolmitriptan should be prioritised for their ability to provide rapid and sustained pain relief. These drugs represent the gold standard for acute migraine treatment.
2. New Drugs as Alternatives: Lasmiditan and gepants should be considered third-line options, reserved for patients unresponsive to or intolerant of triptans. While these drugs offer valuable alternatives, their high costs and specific side effects must be carefully weighed.
3. Enhancing Access: Improving access to effective treatments, particularly triptans, is essential. Policymakers should consider including these drugs in essential medicine lists to ensure broader availability.
4. Personalised Treatment: Given the variability in individual responses to migraine treatments, personalised approaches that consider patient preferences, tolerability, and coexisting medical conditions are critical.

Research Gaps and Future Directions

While the systematic review provides a robust foundation for understanding acute migraine treatments, it also highlights several areas for further research:

• Cardiovascular Safety of Triptans: Revisiting the safety profile of triptans in patients with vascular diseases could address existing concerns and expand their use.
• Cost-Effectiveness: Studies evaluating the cost-effectiveness of newer drugs like lasmiditan and gepants are essential to inform healthcare policies and reimbursement decisions.
• Placebo Response: The high placebo response observed in clinical trials warrants further investigation to improve trial designs and ensure accurate assessment of drug efficacy.
• Individual Patient Data: Incorporating individual patient data in future studies could enhance the understanding of treatment variability and support personalised care.
• Broader Outcomes: Future research should explore outcomes beyond pain relief, such as functional improvements, quality of life, and global functioning.

Clinical and Policy Implications

The results of this analysis have significant clinical and policy implications. By prioritising evidence-based treatment options, clinicians can ensure that patients receive optimal care personalised to their individual needs. Policymakers can play a crucial role by promoting access to effective treatments and addressing barriers such as cost and availability.

One promising step would be the inclusion of the most effective triptans in global essential medicine lists. This move could standardise care and ensure that patients worldwide have access to proven treatments. Additionally, revisiting existing guidelines to incorporate the latest evidence could help clinicians make informed decisions and improve patient outcomes.

Conclusion

Migraine is a complex and pervasive condition that demands effective management strategies. While triptans remain the gold standard for acute treatment, the emergence of newer options like lasmiditan and gepants expands the therapeutic area. However, these newer drugs come with limitations, including high costs and specific adverse effects. Addressing barriers to access, revisiting safety concerns, and prioritising personalised care are essential steps in improving outcomes for individuals with migraine.

By bridging gaps in research and policy, healthcare systems can better support the millions of people affected by migraine, ensuring that they receive timely, effective, and affordable care. Ultimately, the goal is to alleviate the burden of migraine and enhance the quality of life for those living with this debilitating condition.

References

Diener, H.-C. (2020). The risks or lack thereof of migraine treatments in vascular disease. Headache, 60(3), 649–653. https://doi.org/10.1111/head.13749

Karlsson, W. K., Ostinelli, E. G., Zhuang, Z. A., Kokoti, L., Christensen, R. H., Al-Khazali, H. M., Deligianni, C. I., Tomlinson, A., Ashina, H., Ruiz de la Torre, E., Diener, H.-C., Cipriani, A., & Ashina, M. (2024). Comparative effects of drug interventions for the acute management of migraine episodes in adults: systematic review and network meta-analysis. BMJ (Clinical Research Ed.), 386, e080107. https://doi.org/10.1136/bmj-2024-080107