Migraine Treatment Through Compounded Medicine

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Migraine Treatment & Background

Costing about $20 billion a year in medical expenses and loss of productivity, migraines are the sixth most disabling disease in the world (affecting 36 million Americans) and can last from hours to days.1 Triptan medications are the first-line acute treatment for migraines, but these can be expensive, and there are many contraindications for triptan use, such as coronary artery disease, history of stroke, uncontrolled hypertension and other drug interactions. Another alternative is a nasal spray, but Migranal®, a commercial product, costs about $1,500 to $2,500.3 Continue reading to learn more about migraine treatment through the use of compounding.

Even with all these available products, many patients have poor success relieving migraines. A study showed that 56% of patients reported inadequate relief of migraine two hours after usual treatment.4 Currently, there is no specific cure, and since migraines are multifactorial, a combination of drugs targeting different mechanisms may be more effective than monotherapy for migraines.5

Compounded Medications used for Migraine Treatment

Below are further considerations for compounded medications. Alternative options may be a benefit for those who have failed other therapies.


Many patients have migraines with prolonged aura where triptans or ergotamine derivatives cannot help. Ketamine can inhibit this by blocking cortical spreading depression, which is thought to correlate with aura. Furthermore, ketamine has been shown to increase cerebral blood flow in humans.7


Originally an antiepileptic drug now used to treat neuropathic pain in diabetics, gabapentin reduces the release of inflammatory neuropeptides important in headache pain, such as calcitonin gene-related peptide and substance P.8


Tizanidine is a centrally acting, pre-synaptic alpha 2 adrenergic agonist that inhibits the release of norepinephrine and acts as a central muscle relaxant. Studies showed the benefit in the prevention of migraines as well as decreased frequency of headaches (22.83 days to 15.83 days per month).9

Opportunities in Compounding

Pavilion Compounding Pharmacy LLC is able to provide individualized compounded options for patients suffering from migraines. Often, our pharmacists are asked to compound a combination of active pharmaceutical ingredients into transdermal creams, sublingual dosage forms, or nasal sprays. There are various options our pharmacists and prescribers can offer depending on the patient’s situation.

One potential option is topical regional neuro-affective (TRNA) therapy, a relatively new delivery method for patients with migraines. TRNA uses a topical cream and allows direct action to the free nerve endings around the head below the skin surface (stratum corneum). This topical therapy has been studied with sumatriptan to treat migraines.6


CBD oil may be beneficial for managing migraines or other painful ailments. Click here for more information about CBD oil and to purchase online


Magnesium reduces inflammation, relaxes muscles and blood vessels, and modulates calcium ion channels within our cells, which trigger the release of neurotransmitters. Magnesium also decreases the release of substance P, and may be more effective in migraines with auras, possibly because magnesium can prevent cortical spreading depression, which may correlate with aura.10


Lavender oil is known for having a soothing and calming effect. A study showed that 71% of patients inhaling lavender oil for 15 minutes fully or partially improved their headache.11


Lidocaine is a potent local anesthetic agent that may also alleviate migraines. It is hypothesized to act by its membrane-stabilizing effect, which inhibits the release of vasoactive substances from platelets, thus inhibiting the sterile inflammatory response.12


Caffeine is similar in structure with adenosine, an inhibitor of neuronal activity. Activating adenosine receptors (A1 and A2A) leads to antinociception in neuropathic pain and inflammatory models.13


When women have a drop in estrogen and progesterone during their menses, these hormone withdrawals alter the function of neurotransmitters relevant to migraine pathophysiology.14 The mechanism of estrogen withdrawal on migraines is unknown, but estrogen is theorized to have neuroexcitatory effects, which is counterintuitive since estrogen withdrawal seems to trigger migraines.14 Patients with menstrual migraines may benefit from progesterone therapy, which has antiestrogen properties. Additionally, progesterone plays a major role in calming down the stimulatory effect of estrogen.15

Commonly Requested Formulations for Migraine Treatment

Lidocaine HCl 4%/ Ketamine 2.5% Nasal Spray

Lidocaine HCl 4% Isotonic Nasal Spray

Dihydroergotamine Mesylate 2.5mg/mL Nasal Spray

Ketamine 100 mg/mL Nasal Spray

Sumatriptan 5 mg/0.1 mL NasalSpray (MucoLox™)

Ketamine HCl 5%/Gabapentin 6%/ Amitriptyline HCl 3%/ Indomethacin 5%/ TizanidineHCl 0.2%/Lidocaine 2% Topical Lipoderm ActiveMax®

Sumatriptan 4%/Meloxicam 2%/Topiramate 5% Topical Lipoderm

Sumatriptan 5%/Tramadol HCl 5%/Gabapentin 5%/Doxepin HCl 5%/Indomethacin 5% Topical Lipoderm

Baclofen 2%/Ketoprofen 10%/Lidocaine 5%/Gabapentin 5% Topical Lipoderm

Indomethacin 10% Topical Lipoderm

Diclofenac Sodium 4% Topical Lipoderm

Magnesium Sulfate Heptahydrate 10%Topical Lipoderm ActiveMax

Progesterone 25 mg-100mg Rapid DissolveTablet (RDT-Plus™)

Please contact one of our pharmacists today to discuss treatment options. We will be happy to refer you to a provider we work with to find the best option for your individual needs.


1. American Migraine Foundation. (n.d.). Life with headache/migraine. Retrieved from https://americanmigrainefoundation.org/living-with-migraines/life-with-headachemigraine/

2. Botox for chronic migraine. (n.d.) Retrieved from https://migraine.com/ migraine-treatment/botox-for-migraine/

3. Migranal. (n.d.). Retrieved from https://www.goodrx.com/ migranal?gclid=CIrPvZGRrNACFQgIaQodIEwFVQ

4. Lipton, R. B., Munjal, S., Buse, D. C., Fanning, K. M., Bennett, A., & Reed, M. L. (2016). Predicting inadequate response to acute migraine medication: Results from the American Migraine Prevalence and Prevention (AMPP) Study. Headache: The Journal of Head and Face Pain, 56(10), 1635-1648. http://dx.doi.org/10.1111/head.12941

5. Blumenfeld, A., Gennings, C., & Cady, R. (2012). Pharmacological synergy: The next frontier on therapeutic advancement for migraine. Headache: The Journal of Head and Face Pain, 52(4):636-647. http:// dx.doi.org/10.1111/j.1526-4610.2011.02058.x

6. Aung-Din, R. (2009, October). Topical regional neuro-affective (TRNA) therapy: Novel ground-breaking triptan drug delivery for treating migraines. Drug Delivery Technology, 9(9), 44-51.

7. Afridi, S. K., Giffin, N. J., Kaube, H., & Goadsby, P. J. (2013, February

12). A randomized controlled trial of intranasal ketamine in migraine with prolonged aura. Neurology: The Official Journal of the American

Academy of Neurology, 80(7), 642-647. http://dx.doi.org/10.1212/


8. Fehrenbacher, J. C., Taylor, C. P., & Vasko, M. R. (2003, September).

Pregabalin and gabapentin reduce release of substance P and CGRP from rat spinal tissues only after inflammation or activation of protein kinase C. Pain: The Journal of the International Association for the Study of Pain, 105(1-2), 133-141. http://dx.doi.org/10.1016/S0304-


9. Saper, J. R., Winner, P. K., & Lake, A. E., III. (2001, April). An open-label dose-titration study of the efficacy and tolerability of tizanidine hydrochloride tablets in the prophylaxis of chronic daily headache. Headache: The Journal of Head and Face Pain, 41(4), 357-368. http:// dx.doi.org/10.1046/j.1526-4610.2001.111006357.x

10. Tepper, D. (2013, October 1). Magnesium. Headache: The Journal of Head and Face Pain, 53(9), 1533-1534. http://dx.doi.org/10.1111/ head.12220

11. Sasannejad, P., Saeedi, M., Shoeibi, A., Gorji, A., Abbasi, M., & Foroughipour, M. (2012, May). Lavender essential oil in the treatment of migraine headache: A placebo-controlled clinical trial. European Neurology, 67(5), 288-291. http://dx.doi.org/10.1159/000335249

12. Maizels, M., Scott, B., Cohen, W., & Chen, W. (1996, July 24). Intranasal lidocaine for treatment of migraine: A randomized, double-blind, controlled trial. JAMA: The Journal of the American Medical Association, 276(4), 319-321. http://dx.doi.org/10.1001/jama.1996.03540040063034

13. Sawynok, J. (2013). Adenosine and pain. In S. Masino & D. Boison (Eds.), Adenosine: A Key Link between Metabolism and Brain Activity (pp. 343-360). New York, NY: Springer. http://dx.doi.org/10.1007/978-1-4614-3903-5_17

14. Borsook, D., Erpelding, N., Lebel, A., Linnman, C., Veggeberg, R., Grant, P. E., Buettner, C., Becerra, L., & Burstein, R. (2014, August). Sex and the migraine brain. Neurobiology of Diseases, 68, 200-214. http://dx.doi. org/10.1016/j.nbd.2014.03.008

15. Martin, V. T., & Behbehani, M. (2006, March 21). Ovarian hormones and migraine headache: Understanding mechanisms and pathogenesis – part 2. Headache: The Journal of Head and Face Pain, 46(3), 365-386. http://dx.doi.org/10.1111/j.1526-4610.2006.00370.x

16. Consultant’s Corner PCCA Apothagram April 2017