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June is National Migraine and Headache Awareness Month and we want you to be well equipped to care for your migraine and headache patients.

by Catherine Henderson, PharmD, PCCA Clinical Compounding Pharmacist

Migraines affect roughly 14-15% of people globally each year and is just one of more than 200 headache disorders.1 If you’ve ever been a migraine patient or treated a migraine patient, you know how challenging it can be to find the right treatment for acute migraines and the best prophylaxis for chronic migraines.

Acute Migraines

The current standard of care for acute migraine involves use of NSAIDs, ergotamine derivatives, triptans, gepants and ditans. Combination therapy with antiemetics and/or caffeine is also a mainstay of treatment.2 With the loss of isometheptene from the market, many compounders have been searching for a replacement. Since there are so few options for treating migraines, losing an agent that is effective for some patients leaves a gap that can be difficult to fill.

In the PCCA Clinical Services department, we have recently helped many members find an alternative option for patients who were previously using isometheptene. The way that isometheptene is thought to work is by constricting the cranial arteries. Caffeine is another cranial vasoconstrictor, often used in migraine headache formulations.3 For patients who were previously experiencing relief with isometheptene, caffeine would be a reasonable inclusion in their formula.

One of my favorite formulas to recommend for acute migraine is piroxicam 40 mg/ondansetron 2 mg/caffeine troches. The combination of ingredients treats pain and nausea associated with migraine headaches and may provide faster relief due to the route of administration. As an anhydrous formula, both compounders and patients can benefit from the potential of longer beyond-use dates (BUDs).*

Another unique compounding option for acute migraine is intranasal lidocaine, which has been shown to decrease pain intensity and the need for rescue medications. It has been used in varying concentrations of 4-10% in each nostril. The benefit of this formula is that it provides a non-oral, non-injectable route of administration that can be useful in patients experiencing significant nausea. Combining lidocaine with ketorolac in a nasal spray is another option that has been studied and found to have even greater pain relief than lidocaine alone.4 Before choosing this combination, it is important to remember that the use of ketorolac is limited to five days, regardless of route of administration. Evaluating the number of headache days per month that a patient has can help determine if this is an appropriate treatment.5

Migraine Prophylaxis

While the goals of therapy for acute migraine are to relieve symptoms as quickly as possible — with as few side effects as possible — we also need to avoid medication overuse headaches (a headache that results from the frequent use of acute medicines or painkillers).6 In any migraine patient, prevention is an important piece of the puzzle. Current migraine prophylaxis medications include beta-blockers (propranolol), anticonvulsants (valproate, topiramate), antidepressants (amitriptyline) and calcitonin gene-related peptide receptors (CGRPs) (erenumab).7 These prophylactic medications have varying success rates, with the new class of CGRPs having the greatest efficacy.8 Unfortunately, all of these medications come with the risk of adverse events and some come with a significant financial burden.

Alpha-lipoic acid and riboflavin are two agents that have been shown to help with migraine prophylaxis. A study found that a dose of riboflavin 400 mg/day for three months reduced headache days, as well as the duration, frequency and pain score of migraine attacks.9 Another study found similar results with alpha-lipoic acid 300 mg twice daily for 12 weeks.10 Alpha-lipoic acid has also been studied as a preventative agent in adolescents.11 A benefit of these two agents is that they are generally well-tolerated and may be less expensive than other options. These agents can be used alone or as an adjunct to other prophylactic measures.

Treatment Success

In helping your patients navigate migraine treatment and prophylactic options, there are some key strategies and counseling points to consider. Many patients expect full resolution of their migraine symptoms and frequency and may give up on a treatment option too soon if those expectations aren’t managed. Most prophylactic measures must be taken daily for at least two months before a determination can be made about the success of the treatment. Encourage patients to keep a headache diary to collect data about their headache days, severity and other details related to their migraines.6

As pharmacists, we are also uniquely placed to screen for potential medication overuse. Medication overuse headaches are typically seen in patients with 15 or more headache days per month. Most migraine prophylactics won’t be effective in these patients until they go through a detox period from acute migraine treatments.12 The most effective detox programs for medication overuse headaches include complete withdrawal from acute treatments and initiation of preventative medications.13,14

You have the opportunity to make a significant impact on the lives of your patients who suffer with debilitating headache disorders. This article covered just a few of the creative ways that compounding pharmacists are contributing to solutions for migraines.

PCCA members with clinical services access may contact our Clinical Services team for help when compounding for patients with migraines and other compounding concerns.

*USP 795 establishes BUD limits by type of preparation in the absence of a USP−NF Compounded Preparation Monograph or CNSP-specific stability information.

References

  1. Steiner, T. J., & Stovner, L. J. (2023). Global epidemiology of migraine and its implications for public health and health policy. Nature reviews. Neurology, 19(2), 109–117. Accessed May 2024 at https://doi.org/10.1038/s41582-022-00763-1
  2. Ailani, J., Burch, R. C., & Robbins, M. S. (2021). The American Headache Society Consensus Statement: Update on integrating new migraine treatments into clinical practice. Headache: The Journal of Head and Face Pain, 61(7), 1021–1039. Accessed May 2024 https://doi.org/10.1111/head.14153
  3. Drugs.com (Last updated June 2023). Isometheptene, Caffeine, and Acetaminophen Tablets. Accessed May 2024 at https://www.drugs.com/pro/isometheptene-caffeine-and-acetaminophen-tablets.html
  4. Chi, P. W., Hsieh, K. Y., Chen, K. Y., et al. (2019). Intranasal lidocaine for acute migraine: A meta-analysis of randomized controlled trials. PloS one, 14(10), e0224285. Accessed May 2024 at https://doi.org/10.1371/journal.pone.0224285
  5. Pfaffenrath, V., Fenzl, E., Bregman, D., et al. (2012). Intranasal ketorolac tromethamine (SPRIX®) containing 6% of lidocaine (ROX-828) for acute treatment of migraine: Safety and efficacy data from a phase II clinical trial. Cephalalgia, 32(10), 766–777. Accessed May 2024 at https://doi.org/10.1177/0333102412451359
  6. The Migraine Trust. (2021). Medication overuse headache. Accessed May 2024 at https://migrainetrust.org/understand-migraine/types-of-migraine/medication-overuse-headache/
  7. Kumar, A., & Kadian, R. (2020). Migraine Prophylaxis. PubMed; StatPearls Publishing. Accessed May 2024 at https://www.ncbi.nlm.nih.gov/books/NBK507873/
  8. Lampl, C., MaassenVanDenBrink, A., Deligianni, C.I. et al. The comparative effectiveness of migraine preventive drugs: a systematic review and network meta-analysis. J Headache Pain 24, 56 (2023). Accessed May 2024 at https://doi.org/10.1186/s10194-023-01594-1
  9. Chen, Y.-S., Lee, H.-F., Tsai, C.-H., et al. (2021). Effect of Vitamin B2 supplementation on migraine prophylaxis: a systematic review and meta-analysis. Nutritional Neuroscience, 1–12. Accessed May 2024 at https://doi.org/10.1080/1028415X.2021.1904542
  10. Kelishadi, M.R., Naeini, A.A., Khorvash, F. et al. The beneficial effect of Alpha-lipoic acid supplementation as a potential adjunct treatment in episodic migraines. Sci Rep 12, 271 (2022). Accessed May 2024 at https://doi.org/10.1038/s41598-021-04397-z
  11. Puliappadamb, H. M., Satpathy, A. K., Mishra, et al. (2023). Evaluation of Safety and Efficacy of Add-on Alpha-Lipoic Acid on Migraine Prophylaxis in an Adolescent Population: A Randomized Controlled Trial. Journal of clinical pharmacology, 63(12), 1398–1407. Accessed May 2024 at https://doi.org/10.1002/jcph.2331
  12. D'Amico, D., & Tepper, S. J. (2008). Prophylaxis of migraine: general principles and patient acceptance. Neuropsychiatric disease and treatment, 4(6), 1155–1167. Accessed May 2024 at https://doi.org/10.2147/ndt.s3497
  13. Carlsen, L. N., Munksgaard, S. B., Jensen, R. H. et al. (2018). Complete detoxification is the most effective treatment of medication-overuse headache: A randomized controlled open-label trial. Cephalalgia : an international journal of headache, 38(2), 225–236. Accessed May 2024 at https://doi.org/10.1177/0333102417737779
  14. Nielsen, M., Carlsen, L. N., Munksgaard, S. B., et al. (2019). Complete withdrawal is the most effective approach to reduce disability in patients with medication-overuse headache: A randomized controlled open-label trial. Cephalalgia, 39(7), 863–872. Accessed May 2024 at https://doi.org/10.1177/0333102419828994

These statements are provided for educational purposes only. They have not been evaluated by the Food and Drug Administration, and are not to be interpreted as a promise, guarantee or claim of therapeutic efficacy or safety. The information contained herein is not intended to replace or substitute for conventional medical care or encourage its abandonment.



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