New Migraine Treatments Provide More Options for Easing, Preventing Symptoms

Migraines affect a little over 10% of the global population and are still not well understood. Fortunately, recent advancements in treatments have given doctors and patients more tools in their toolbox to prevent or ease migraine symptoms.

A migraine is defined as a recurrent throbbing headache that typically affects one side of the head, resulting in moderate to severe pain. It is often accompanied by additional symptoms such as nausea, fatigue, and sensitivity to light and sound.

Although the definitive cause of the condition is not fully understood, it is postulated that migraines are caused by changes in the trigeminal nerve and neurotransmitter imbalances. As neurotransmitters, such as serotonin, decrease in levels, the body releases neuropeptides, which signal the cranial blood vessels to dilate and allow in more blood.

Migraines can be triggered by different things in different people. Various triggers have been observed, including certain foods, alcohol, and sensory stimuli such as loud sounds and sun glare. The first non-drug step in treating migraines is to identify personal triggers and try to avoid them as best as possible. Many patients start off by creating a log or diary of headaches to help identify triggers and patterns.

Prior to visiting some of the novel treatments for migraines, it is beneficial to review the previously established regimens. Generally, migraine therapy can be categorized into 2 main segments: acute drug treatment and prophylactic drug treatment.

To treat acute symptoms, many undiagnosed patients who suffer from migraines start by taking over-the-counter analgesics such as acetaminophen (Tylenol; Johnson & Johnson), ibuprofen (Motrin; McNeil Consumer Healthcare), naproxen (Aleve; Bayer), or combo agents that contain aspirin, acetaminophen, and caffeine (Excedrin). These options will generally alleviate symptoms for a more mild to moderate form of migraine, but more moderate to severe forms will tend to require prescription agents.

The most common prescription options for acute treatment include serotonin receptor agonists (triptans), ergotamine drugs, and butalbital-containing drugs.

Triptans are selective agonists for the 5-HT1 receptor. They work by constricting blood vessels in the brain, which inhibits release of neuropeptides and decreases the transmission of pain. Triptans are still considered first-line in the treatment of migraines. Some examples of triptans include sumatriptan (Imitrex; GSK), rizatriptan (Maxalt; Merck), zolmitriptan (Zomig; AstraZeneca), and eletriptan (Relpax; Pfizer).

Triptans are mostly manufactured as immediate release tablets, which allow for a fairly quick onset of action. There are, however, a few special formulations that allow for an even quicker onset such as sumatriptan, rizatriptan, and zolmitriptan orally disintegrating tablets, zolmitriptan nasal spray, and sumatriptan subcutaneous injections.

Ergotamine-containing products are nonselective serotonin receptor agonists and are considered second-line. These are generally reserved for patients who find no relief from triptans. Ergotamine and caffeine (Cafergot; Altura Pharmaceuticals) is available as tablets and as a suppository (Migergot; Cosette Pharmaceuticals). Dihydroergotamine comes as an injection (D.H.E. 45; Valeant) and a nasal spray (Migranal; Valeant).

Butalbital-containing products, opioids, and other controlled pain medications, although sometimes prescribed, aren’t recommended for migraine treatment due to their abuse/dependence potential. They are often used in cases where no other treatment seems to be beneficial. Examples of butalbital-containing products include acetaminophen/butalbital/caffeine (Fioricet; Actavis) and aspirin/butalbital/caffeine (Fiorinal; Allergan). Both of these combinations also have a version with codeine as an extra ingredient.

In terms of prophylactic treatment, the goal is to decrease the frequency of migraine attacks. Patients qualify for prophylactic treatment when they need to use acute treatments for 2 or more days in 1 week or for 3 times or more per month. Beta blockers, such as propranolol (Inderal; AstraZeneca) and metoprolol (Lopressor; Novartis), and antiepileptics, such as divalproex (Depakote; Abbvie) and topiramate (Topamax; Janssen), are often used daily to prevent migraine attacks.

Botulinum toxin type A (Botox; Allergan) is used for chronic migraine prophylaxis. It is injected into the nerves around the pain fibers involved in headaches. It then blocks the release of chemicals and prevents the chain of pain activation. One treatment will last approximately 10 to 12 weeks.

A fairly new class used in the prevention of migraines is the calcitonin gene-related peptide (CGRP) receptor antagonist. CGRP is a protein involved in the cause of migraine, and by modulating levels in the body, prevention is attained. There are 2 types of CGRP inhibitors: monoclonal antibodies and gepants.

The monoclonal antibodies group target either CGRP directly or the receptor to which the CGRP binds. Erenumab (Aimovig; Amgen/Novartis), fremanezumab (Ajovy; Teva), and galcanezumab (Emgality; Eli Lilly) are all subcutaneous injections generally used once a month. Eptinezumab (Vyepti; Lundbeck) is a new intravenous version approved in 2020 that is given every 3 months.

Gepants are an unofficial name for a new oral formulation type of CGRP receptor antagonists, which include ubrogepant (Ubrelvy; Allergan), rimegepant (Nurtec ODT; Biohaven), and atogepant (Qulipta; Abbvie). These medications block the CGRP receptor and are effective at both relieving migraines and preventing them.

One of the newest drugs released for migraine treatment is lasmiditan (Reyvow; Eli Lilly), which is the first and only type in its class of serotonin 5-HT1F agonists. It works on specific receptors found on nerves that are responsible for transmitting pain rather than on blood vessels. This means that it produces migraine relief without having any constriction effects on blood vessels, making it more suitable for use in patients who also have vascular conditions.

Dihydroergotamine was previously mentioned in the ergotamine class; however, the FDA has recently approved a new nasal spray formulation (Trudhesa; Impel Neuropharma) which uses a new proprietary delivery system that allows the drug to go deeper into the nasal cavity, increasing absorption.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are a common class of analgesics used to relieve migraine pain. OTC versions such as naproxen and ibuprofen were mentioned previously. There is a new prescription liquid NSAID, celecoxib (Elyxyb; Dr. Reddy’s), that is pending approval.

Finally, neuromodulation devices are becoming more popular as preventive treatment. A device that manipulates electrical currents and/or magnets are used to modify brain activity. There are currently four devices that have been approved by the FDA and are considered to have minimal risk or little to no adverse effects.

As crucial partners in effecting the best health outcomes for patients, it is important for pharmacists to keep up to date with advancements in migraine treatments, which can potentially improve the health and quality of life for millions of people.

About the Author

Steven P. Mathew, PharmD, is a senior pharmacist with Community Care Rx, which is a full-service, long-term care pharmacy with offices in Hempstead, New York and Totowa, New Jersey.