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Selecting migraine treatments for your patient

What should you consider?
Read time: 40 mins
Last updated:16th Mar 2022
Published:16th Mar 2022

It can be challenging to navigate through the evolving landscape of treatments for acute and preventive treatment of migraine, particularly for patients with comorbid conditions.

  • Review key considerations when selecting pharmacological options for migraine treatment
  • Learn about key factors that influence choice of preventive migraine treatment, particularly those that target calcitonin gene-related peptide (CGRP) and its receptor
  • Find out more about approaches to improve patient involvement in the decision-making process

In this third and final article in the three-part Insight Article Series on Managing Migraine, join Professor Egilius Spierings to learn more about selecting a migraine treatment, with a focus on preventive treatments and anti-CGRPs.

Selecting a migraine treatment – general considerations

An individualised approach is recommended when selecting a migraine treatment, considering factors such as1,2:

  • The type of migraine (episodic or chronic), symptom profile, frequency and degree of disability
  • Whether the patient has severe nausea and/or vomiting, in which case a treatment administered via a non-oral route may be considered
  • Treatment history, the possibility of medication overuse and prior treatment failures
  • Comorbidities
  • Concurrent medications
  • The efficacy, tolerability and safety profile of treatments
  • Patient preferences

The 2021 consensus statements from the American Headache Society (AHS)2 and the European Headache Federation and the European Academy of Neurology1 generally recommend an adequate trial of established treatments for acute and/or preventive treatment of migraine before initiating use of migraine-specific acute and preventive treatments1,2. The 2021 AHS Consensus Statement noted this hierarchical approach was recommended because of cost considerations and the absence of published evidence to support or refute this approach, although this may evolve as more evidence emerges2.

Choosing a preventive migraine treatment

For an overview of key considerations when selecting a preventive migraine treatment1–5, view and download our informative infographic.

Professor Spierings explains some key factors to keep in mind when considering an anti-CGRP treatment, and the importance of involving patients in the decision-making process.

 



When is preventive treatment recommended for managing migraine?

Preventive migraine treatments can reduce the frequency, severity and duration of migraine attacks, improve function and quality of life, and may help to avoid escalating use of acute treatment, which is associated with medication overuse headache2,6.

Consider a preventive migraine treatment if migraine attacks are severe, disabling or frequent, and for patients who cannot tolerate or are nonresponsive to acute treatment2.

What are the treatment options for migraine prevention?

Treatment options for migraine prevention are summarised in Table 1.

Table 1. Preventive treatments for migraine (Adapted1)7–15. BID, twice daily; CGRP, calcitonin gene-related peptide; IM, intramuscular; IV, intravenous; MAOIs, monoamine oxidase inhibitors; OD, once daily; SC, subcutaneous; SSRIs, selective serotonin reuptake inhibitors. *Intended as a brief, high-level summary of contraindications, refer to Prescribing Information for a comprehensive list of all relevant contraindications, precautions and warnings for each medicine.

Drugs
Administration route and frequency
Contraindications*
First-line
Beta blockers
Atenolol, oral BID
Bisoprolol, oral OD
Metoprolol, oral BID or modified release OD
Propranolol, oral OD or BID in long-acting formulations

Asthma
Cardiac failure
Raynaud’s disease
Atrioventricular block
Depression


Angiotensin II receptor blocker
Candesartan, oral OD
Co-administration of aliskiren

Anticonvulsant
Topiramate, oral OD

Nephrolithiasis
Pregnancy, lactation
Glaucoma
Second-line
Tricyclic antidepressant
Amitriptyline, oral OD (at night)

Age <6 years
Heart failure
Co-administration with MAOIs and SSRIs
Glaucoma
Calcium antagonist
Flunarizine, oral OD
Parkinsonism
Depression
Anticonvulsant
Sodium valproate, oral OD
Liver disease
Thrombocytopenia
Women of childbearing potential
Third-line
Botulinum toxin
Onabotulinumtoxin A, IM injection every 12 weeks
Contraindications include infection at injection site

CGRP monoclonal antibodies
Erenumab, SC injection monthly
Fremanezumab, SC injection monthly or quarterly
Galcanezumab, SC injection monthly
Epitnezumab, IV infusion every 3 months
Hypersensitivity/serious hypersensitivity to the active substance or any of its excipients






CGRP small molecule antagonists (gepants)
Atogepant, oral OD
Rimegepant, oral every other day
Atogepant: No contraindications listed in US prescribing information

Rimegepant: History of hypersensitivity reactions to rimegepant or its components

How can comorbidities influence selection of a preventive treatment for migraine?

Comorbidities in patients with migraine often include anxiety, depression, sleep disturbances and chronic pain3.

Consider a preventative treatment option with known efficacy for relevant comorbid conditions, and consider avoiding treatments that might exacerbate comorbidies or interact with co-administered medications1,2

Recommendations and considerations for migraine prevention in specific populations are summarised in Table 21,2.

Table 2. Recommendations for migraine prevention in specific populations1,2,5,16,17. CGRP, calcitonin gene-related pepide; mAbs, monoclonal antibodies; MAOIs, monoamine oxidase inhibitors; NSAID, non-steroidal anti-inflammatory drug. *A decision to prescribe preventive migraine treatment for women who are pregnant should be based on individual needs and available safety data, weighing up the risks of uncontrolled migraine on pregnancy/lactation versus those of the preventive medication2.

Patient population/ comorbidity Considerations for migraine prevention
All women of childbearing age · Consider the potential for pregnancy before starting any treatment, including the benefits and risks of the treatment to both the mother and child, based on available data
· Sodium valproate is contraindicated
Children/adolescents · Options include propranolol, amitriptyline or topiramate
· Amitriptyline is contraindicated in patients aged <6 years
Hypertension · Consider antihypertensives approved for prevention of migraine (e.g. propranolol, candesartan)
· Erenumab has a warning/precaution for new-onset or worsening of pre-existing hypertension in US prescribing information
Medication overuse · Options include topiramate, onabotulinumtoxin A
  or CGRP mAbs
· Amitriptyline may be used to treat withdrawal symptoms
Menstual-related migraine · Consider perimenstrual preventive therapy with a long-acting NSAID or triptan
Mood disorders (depression, anxiety) · Depression: Amitriptyline may provide benefit. Note co-administration of amitriptyline with MAOIs and SSRIs is contraindicated, and flunarizine and beta blockers are contraindicated in depression.
· Anxiety: Propranolol may be useful (caution regarding mood and vivid dreams)
Obesity/overweight · Topiramate is preferred, as it may be useful for weight loss
Older people · Consider the higher risks of secondary headache, comorbidities and adverse effects with older age
Sleep disorders · Amitriptyline may provide benefit (note drowsiness is a very common adverse effect)
Women who are pregnant or breastfeeding, or trying to conceive · It is generally recommended to avoid use of preventive migraine treatments; however, this should be determined on a case-by-case basis*
· Topiramate, candesartan and sodium valproate are contraindicated

Choosing between anti-CGRP treatments

All four CGRP monoclonal antibodies (CGRP mAbs) are approved in the US for prevention of migraine in adults 8,9,11,12, and in Europe for prophylaxis of migraine in adults who have at least 4 migraine days per month 13–15,18 . In Europe, CGRP mAbs are recommended as a third-line option for prevention of migraine1.

Two small molecule CGRP antagonists (gepants; atogepant and rimegepant) are approved in the US for preventive treatment of migraine in adults7,10. The 2021 American Headache Society Consensus Statement notes treatment plans for gepants should be based on regimens used in clinical trials and tailored to each patient1. In February 2022, rimegepant received a positive opinion from the European Medicine Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) for use in migraine prevention19.

The first head-to-head study of a CGRP mAb and gepant is underway (CHALLENGE-MIG20,21), and it remains to be seen whether the results of this study will influence migraine treatment selection.

Brief details on some key considerations are provided below.

Route and frequency of treatment administration

While some patients with migraine may prefer oral treatments2, treatments administered subcutaneously or intravenously require less frequent dosing1.

Drug interactions

Gepants

Dose adjustment is required for atogepant when co-administered with strong CYP3A4 inhibitors, strong CYP3A4 inducers and organic anion transporting polypeptide (OATP) inhibitors7.

Avoid concomitant administration of rimegepant with strong CYP3A4 inhibitors, strong and moderate inducers of CYP3A, and inhibitors of P-glycoprotein or breast cancer resistance protein10. Rimegepant dosing should be avoided within 48 hours when concomitantly administered with moderate CYP3A4 inhibitors10.

CGRP mAbs

No formal drug–drug interaction studies have been conducted with CGRP mAbs. However, CGRP mAbs are not metabolised by liver enzymes, so are not expected to interact with drugs that are substrates for those enzymes12–15.

Treating patients with renal or hepatic impairment

No dose adjustment is required for CGRP mAbs, atogepant or rimegepant in patients with mild or moderate renal or hepatic impairment7–15. For patients with severe renal impairment, dose adjustment is required for atogepant, but not for rimegepant7,10. For patients with end-stage renal disease (CrCl <30 mL/min), rimegepant should be avoided, and dose adjustment is required for atogepant. For patients with severe hepatic impairment, both atogepant and rimegepant should be avoided7,10.

For CGRP mAbs, there is limited data available from patients with renal and hepatic impairment from clinical trials12–15, however, and neither is expected to affect the pharmacokinetics of monoclonal antibodies14.

Warnings and precautions

Gepants

A warning/precaution for hypersensitivity reactions is listed in the prescribing information for rimegepant10, and no precautions or warnings are listed for atogepant7.

CGRP mAbs

Warnings/precuations for erenumab include constipation with serious complications and hypersensitivity reactions 8,14, and new-onset or worsening of pre-existing hypertension (US only)88,14. Components of the erenumab injection device contain dry natural rubber latex, which may cause allergic reactions in individuals sensitive to latex8,14.

For all CGRP mAbs, there is a lack of safety data in patients with certain major cardiovascular diseases13–15,22, and a lack of data for eptinezumab in patients with a history of neurological diseases or those with uncontrolled/untreated psychiatric conditions22.

Involving patients in the decision-making process

Preventive medications for migraine have historically been associated with low long-term adherence, due to suboptimal efficacy and poor tolerability2.

Involving patients in the decision-making process may improve treatment outcomes, adherence, persistence and treatment satisfaction3–5

A balanced discussion about the range of treatment options for migraine may include efficacy, adverse effects, long-term safety and mechanism of action5. Consider the patient’s preferences, circumstances and values2,3, particularly relating to convenience, tolerability and cost2, before agreeing on a treatment plan with each patient5. Ensure patients are aware that it can take several weeks or months for the efficacy of a preventive treatment to be determined1, and consider appropriate timeframes for review23.

About Professor Egilius Spierings


Professor Egilius Spierings is the medical director of The Boston Headache Institute at Boston PainCare in Waltham, Massachusetts, United States. He is a former clinical professor of neurology and craniofacial pain at Tufts University Schools of Medicine and Dental Medicine in Boston, Massachusetts, and a former associate clinical professor of neurology at Harvard Medical School.

Disclosures

Professor Spierings is a member of the speaker bureaus of Abbvie, Amgen, Biohaven Pharmaceuticals, Lundbeck, Teva Pharmaceuticals, and Eli Lilly.

Views and opinions expressed by Professor Spierings are based on his clinical knowledge and experience, and do not represent the views of EPG Health or Medthority. This content should not be taken as medical advice and is for informational purposes only. Please consult your regional clinical practice guidelines for clinical practice recommendations in your area.

Learn more about the real-world evidence on CGRP mAbs for managing migraine

Explore the long-term evidence for safety and efficacy of CGRP mAbs for migraine

References

  1. Eigenbrodt AK, Ashina H, Khan S, Diener HC, Mitsikostas DD, Sinclair AJ, et al. Diagnosis and management of migraine in ten steps. Nature Reviews Neurology. 2021;17(8):501–514.
  2. Ailani J, Burch RC, Robbins MS. The American Headache Society Consensus Statement: Update on integrating new migraine treatments into clinical practice. Headache. 2021;61(7):1021–1039.
  3. Xu X, Ji Q, Shen M. Patient Preferences and Values in Decision Making for Migraines: A Systematic Literature Review. Pain Research and Management. 2021;2021. doi:10.1155/2021/9919773.
  4. Barbosa CD, Balp MM, Kulich K, Germain N, Rofail D. A literature review to explore the link between treatment satisfaction and adherence, compliance, and persistence. Patient Preference and Adherence. 2012;6:39–48.
  5. Blumenfeld AM. Clinician-Patient Dialogue About Preventive Chronic Migraine Treatment. Journal of Primary Care and Community Health. 2020;11. doi:10.1177/2150132720959935.
  6. Ray J. The state of migraine: An update on current and emerging treatments. Australian Journal of General Practice. 2021;50(12):915–921.
  7. US Food and Drug Administration. Full Prescribing Information - Atogepant. 2021. Last revised September 2021 https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/215206Orig1s000lbl.pdf. Accessed 4 February 2022.
  8. US Food and Drug Administration. Full prescribing information - erenumab. 2021. Last revised February 2021 https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/761077s009lbl.pdf. Accessed 26 October 2021.
  9. US Food and Drug Administration. Full prescribing information - galcanezumab. 2021. Last revised March 2021 https://pi.lilly.com/us/emgality-uspi.pdf. Accessed 26 October 2021.
  10. US Food and Drug Administration. Full prescribing information - rimegepant. 2021. Last revised May 2021 https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/212728s006lbl.pdf. Accessed 15 February 2022.
  11. US Food and Drug Administration. Full prescribing information - fremanezumab. 2020. Last revised January 2020 https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/761089s002lbl.pdf. Accessed 26 October 2021.
  12. US Food and Drug Administration. Full prescribing information - eptinezumab. 2020. Last revised February 2020 https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/761119s000lbl.pdf. Accessed 26 October 2021.
  13. Committee for Medicinal Products for Human Use (CHMP). Ajovy (fremanezumab), Summary of Product Characteristics. EPAR. Teva GmbH. 2019. Last updated September 2021 https://www.ema.europa.eu/en/documents/product-information/ajovy-epar-product-information_en.pdf. Accessed 26 October 2021.
  14. Committee for Medicinal Products for Human Use (CHMP). Aimovig (erenumab), Summary of Product Characteristics. EPAR. Novartis Europharm Limited. 2018. Last updated December 2021 https://www.ema.europa.eu/en/documents/product-information/aimovig-epar-product-information_en.pdf. Accessed 26 October 2021.
  15. Committee for Medicinal Products for Human Use (CHMP). Emgality (galcanezumab), Summary of Product Characteristics. EPAR. Eli Lilly Nederland B.V. 2018. Last updated July 2021 https://www.ema.europa.eu/en/documents/product-information/emgality-epar-product-information_en.pdf. Accessed 26 October 2021.
  16. Ha H, Gonzalez A. Migraine headache prophylaxis. American Family Physician. 2019;99(1):17–24.
  17. Electronic Medicines Compendium. Summary of product characteristics - amitriptyline 10 mg tablets BP. 2021 https://www.medicines.org.uk/emc/product/5698/smpc#gref. Accessed 15 February 2022.
  18. H. Lundbeck A/S. Vyepti® (eptinezumab) approved by the EU Commission for the preventive treatment of migraine in adults. Corporate Release. 2022. https://news.cision.com/h--lundbeck-a-s/r/vyepti---eptinezumab--approved-by-the-eu-commission-for-the-preventive-treatment-of-migraine-in-adul,c3491409. Accessed 7 February 2022.
  19. European Medicines Agency. Meeting highlights from the Committee for Medicinal Products for Human Use (CHMP) 21-24 February 2022. 2022. https://www.ema.europa.eu/en/news/meeting-highlights-committee-medicinal-products-human-use-chmp-21-24-february-2022. Accessed 3 March 2022.
  20. Lilly. Emgality® versus Nurtec® ODT head-to-head migraine preventive treatment study now enrolling patients. News Release. 2021. https://investor.lilly.com/news-releases/news-release-details/emgalityr-versus-nurtecr-odt-head-head-migraine-preventive. Accessed 7 February 2022.
  21. Eli Lilly and Company. A study of galcanezumab (LY2951742) in adult participants with episodic migraine (CHALLENGE-MIG). clinicaltrials.gov. 2021. https://clinicaltrials.gov/ct2/show/NCT05127486. Accessed 7 February 2022.
  22. Committee for Medicinal Products for Human Use (CHMP). Vyepti (eptinezumab), Summary of Product Characteristics. EPAR. H. Lundbeck A/S. 2022 https://www.ema.europa.eu/en/documents/product-information/vyepti-epar-product-information_en.pdf. Accessed 3 March 2022.
  23. Trigo-López J, Guerrero-Peral ÁL, Sierra Á, Martínez-Pías E, Gutiérrez-Sánchez M, Huzzey E, et al. Patients and general practitioners assessment of the main outcomes employed in the acute and preventive treatment of migraine: a cross sectional study. BMC Neurology. 2021;21(1). doi:10.1186/s12883-021-02220-w.
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