Elsevier

The Lancet

Volume 397, Issue 10283, 17–23 April 2021, Pages 1505-1518
The Lancet

Series
Migraine: integrated approaches to clinical management and emerging treatments

https://doi.org/10.1016/S0140-6736(20)32342-4Get rights and content

Summary

Migraine is a highly disabling neurological disorder that directly affects more than 1 billion individuals worldwide. Available treatment options differ between countries and include acute, preventive, and non-pharmacological therapies. Because of major progress in the understanding of migraine pathogenesis, novel mechanism-based medications have emerged and expanded the armamentarium of treatments. We provide a comprehensive overview of the current standard of care that will enable informed clinical management. First, we discuss the efficacy, tolerability, and safety profile of various pharmacological therapies for acute and preventive treatment of migraine. Second, we review the current knowledge on non-pharmacological therapies, such as neuromodulation and biobehavioural approaches, which can be used for a multidisciplinary approach to clinical management. Third, we emphasise that any effective treatment strategy starts with building a therapeutic plan tailored to individual clinical characteristics, preferences, and needs. Finally, we explore the outlook of emerging mechanism-based treatments that could address unmet challenges in clinical management of migraine.

Introduction

Migraine is a major public health challenge that is insufficiently recognised and incurs considerable individual and societal costs.1 Migraine ranks as the leading cause of years lived with disability worldwide in individuals younger than 50 years.2 The current armamentarium of treatments includes acute medications, preventive medications, and non-pharmacological therapies. Despite an array of available treatment options, there are ongoing challenges with undertreatment, adherence, and access. In 2018, these challenges were highlighted by population-based data from six European countries.3 In individuals with migraine, triptans were used by only 3–22%, whereas preventive medications were used by 2–14% of eligible patients. Therefore, improvements need to be made so that the current standard of care is applied consistently and effectively in clinical practice. In this Series paper, we discuss available evidence in the context of optimising patient care and minimising unnecessary treatment exposure and failure. We present each therapeutic approach sequentially, with a review of available evidence in terms of efficacy, tolerability, and safety profile. We also discuss how recently approved (over the past 3 years) and emerging treatments could be integrated into clinical practice.

Section snippets

Acute treatment

Medication therapy is the mainstay of acute treatment of migraine (table 1). The International Headache Society has defined two clinical outcomes for treatment success in randomised controlled trials (RCTs). The first outcome is defined as freedom from pain within 2 h after treatment. The second outcome is defined as absence of the most bothersome migraine-associated symptom (ie, nausea, vomiting, photophobia, or phonophobia) within 2 h after treatment.24 Acute medications include paracetamol,

Preventive treatment

Preventive medications are used to reduce the frequency, severity, or duration of migraine attacks in affected individuals in whom use of acute medications does not suffice as a standalone treatment strategy. According to consensus guidelines from the European Headache Federation, initiation of preventive therapy is recommended for individuals who have migraine attacks that occur at least 2 days per month and are associated with impaired quality of life.28 Additionally, their migraine should

Non-pharmacological therapeutic approaches

Several non-pharmacological therapies have benefits for individuals with migraine and can be used alone or as adjunct therapy to pharmacological drugs. They provide a multidisciplinary approach to clinical management while also minimising unnecessary drug exposure. The non-pharmacological therapies with the strongest evidence include neuromodulation and biobehavioural therapies, such as cognitive behavioural therapy (CBT), biofeedback, and relaxation training. Less evidence supports the use of

Patient centricity

Migraine is a heterogeneous disorder and its clinical manifestations can vary within and between patients over time. To optimise clinical care, there is an urgent need for therapeutic approaches to recognise the clinical characteristics, preferences, and needs of individual patients, thereby avoiding a general standardised approach. Agreed realistic objectives are important and any therapeutic strategy must also account for local resources and access to medications.

Future research for intervention studies and guideline development

Prospective, randomised, controlled clinical trials are the gold standard to assess the efficacy and safety of interventions for migraine. The International Headache Society guidelines for controlled trials of acute and preventive treatments for migraine25, 110 have assured the continued viability of RCTs. However, RCT data are from carefully selected migraine populations that might not adequately reflect patients in real-world practice. Thus, concerted efforts are needed to optimise RCT data

Emerging treatments

The past decade has seen major progress in the development of novel treatments for migraine, with results from ongoing trials still pending (NCT03855137, NCT03700320, NCT04197349, and NCT03238781). Emerging therapies for migraine prevention include two CGRP receptor antagonists, atogepant and rimegepant, and a monoclonal antibody (Lu-AG09222) that inhibits the signalling molecule pituitary adenylate cyclase-activating polypeptide (PACAP).

Conclusion

There have been great advances in the treatment of migraine over the past 5 years, with novel mechanism-based treatments that complement standard of care and mitigate the disease burden attributed to migraine. Many therapeutic options are available to effectively treat migraine but several obstacles remain, including the current knowledge gap related to tailored treatment for individual patients. First, there needs to be more research on the biological underpinnings of migraine to identify

Search strategy and selection criteria

We searched MEDLINE (from database inception to Jan 1, 2020), and Embase (from database inception to Jan 1, 2020) for original research articles, and systematic reviews and meta-analyses. We used the search terms “migraine” in combination with the terms “acute”, “preventive”, “treatment”, “medication”, “drug, “complimentary”, “management”, “cognitive”, “therapy”, “device”, “diet”, “sleep”, “acupuncture”, “education”, “novel”, “economics” and “emerging”. We mainly selected publications from the

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