Fans of tennis superstar Serena Williams know that she has played through several conditions — knee injuries, shoulder problems, and pregnancy. But most do not know that she also, at times, played while suffering from migraine headaches.
The 23-time Grand Slam singles champ experienced headaches as a child, but didn’t realize that they were migraines until she was in her 20s. Playing in the intense sunlight became particularly painful. Williams told People magazine that she was reluctant to tell her father (her coach at the time), about the headaches she was experiencing.
“Migraine isn’t a knee injury — it’s something you can’t physically see,” she said. “You can’t really say, ‘Oh, Dad, I have a migraine. I’m going to stop playing.’ People are like, ‘I don’t see swelling. I don’t see bruising. Tough it out.’ I got used to playing through the pain.”
Fortunately, Williams’ migraine attacks were infrequent enough that she was, for the most part, able to deal with them. Fast forward to this year and the pandemic quarantine. Williams said that being at home with husband Alexis Ohanian and their almost 3-year-old daughter Olympia was “incredibly stressful” and triggered migraines nearly every day. She spoke to her doctor, who prescribed ubrogepant (Ubrelvy). She says it worked so well that she signed up to be a spokesperson for the medication.
Serena says she is preparing for the upcoming U.S. Open (scheduled for Aug 31- Sept 13), which will be held without fans. She says: “I’ve always played with such a big crowd. Without fans, how will I do? I don’t even know. But I look at it as another experience — a wild experience.”
Advances in the Treatment of Migraines
Migraine treatment is aimed at relieving symptoms and preventing additional attacks. Quick steps to ease symptoms may include napping or resting with eyes closed in a quiet, darkened room; placing a cool cloth or ice pack on the forehead; and drinking lots of fluid, particularly if the migraine is accompanied by vomiting. Small amounts of caffeine may help relieve symptoms during a migraine’s early stages.
Drug therapy for migraine is divided into acute and preventive treatment. Acute or “abortive” medications are taken as soon as symptoms occur to relieve pain and restore function. Preventive treatment involves taking medicines daily to reduce the severity of future attacks or keep them from happening.
Acute Treatments
Acute treatment for migraine may include triptans, ergot derivative drugs, non-prescription analgesics or over-the-counter drugs, and combinations.
Triptan drugs increase levels of the neurotransmitter serotonin in the brain. Serotonin causes blood vessels to constrict and lowers the pain threshold. Triptans — the preferred treatment for migraine — ease moderate to severe migraine pain and are available as tablets, nasal sprays, and injections. Currently available triptans include sumatriptan, zolmitriptan, naratriptan, rizatriptan, almotriptan, eletriptan, and frovatriptan. Sumatriptan is available as a subcutaneous injection (usually administered by autoinjector in the thigh), as a nasal spray, as a nasal powder, or orally. Zolmitriptan is also available for both nasal and oral use; the others are available for oral use only.
Ergot derivative drugs bind to serotonin receptors on nerve cells and decrease the transmission of pain messages along nerve fibers. They are most effective during the early stages of migraine and are available as nasal sprays and injections.
Non-prescription analgesics like acetaminophen can ease the pain of less severe migraine headaches, and over-the-counter nonsteroidal anti-inflammatory drugs such as ibuprofen or aspirin can reduce inflammation and alleviate pain as well.
Combination analgesics involve a mix of drugs such as acetaminophen plus caffeine and/or a narcotic for migraine that may be resistant to simple analgesics.
CGRP Inhibitors
CGRP (calcitonin gene-related peptide) is a 37-amino acid neuropeptide. It is a highly potent vasodilator, is primarily released from sensory nerves (particularly trigeminal ganglion cells responsible for sensation in the face), and is implicated in pain pathways.
CGRP inhibitors block the effects of CGRP and are more recent members of the migraine drug armamentarium. There are two types of CGRP inhibitors — monoclonal antibodies and CGRP receptor antagonists (gepants). Monoclonal antibodies target either CGRP or the CGRP receptor and are used for migraine prevention (more about this later).
Gepants are small molecules that can block CGRP receptors and can be used in the acute treatment of migraines. They can rapidly penetrate the brain, so they work quickly and are recommended for use at the first sign of symptoms.
The first generation of gepants, discovered 15 years ago, was abandoned because of liver toxicity. However, the second generation, available now, does not seem to have this problem. There are currently two FDA-approved gepants — ubrogepant, approved in December 2019, and rimegepant (Nurtec), approved in February 2020.
An advantage of gepants is that they do not cause constriction of blood vessels (as triptans can), which could make them attractive alternatives for patients who have vascular or heart disease or stroke.
Another gepant, vazegepant (recently renamed zavegepant) is not yet available, but was shown to have a positive effect in clinical trials.
Relief from migraine symptoms can occur within 2 hours. The most common side effects in trials were nausea, tiredness, and dry mouth.
Migraine Prevention
Perhaps even more important than treatment of migraine is the ability to prevent a migraine in the first place. In general, prevention should be considered if migraines occur one or more times weekly, or are less frequent but disabling.
Preventive medicines are also recommended for individuals who take symptomatic headache treatment more than three times a week. Physicians recommend that a migraine sufferer take one or more preventive medications for 2-3 months to assess drug effectiveness unless intolerable side effects occur.
Several preventive medicines for migraine were initially marketed for conditions other than migraine.
Anticonvulsants: Although they were originally developed for treating epilepsy, these drugs increase levels of certain neurotransmitters and dampen pain impulses.
Beta-blockers, drugs for treating high blood pressure, are often effective for migraine.
Calcium channel blockers are medications that are also used to treat high blood pressure and help to stabilize blood vessel walls. These drugs appear to work by preventing the blood vessels from either narrowing or widening, which affects blood flow to the brain.
Antidepressants are drugs that work on different chemicals in the brain. They increase the production of serotonin and may also affect levels of other chemicals, such as norepinephrine and dopamine. The types of antidepressants used for migraine treatment include selective serotonin reuptake inhibitors, norepinephrine reuptake inhibitors, and tricyclic antidepressants.
Newer Methods/Medications for Migraine Prevention
CGRP Inhibitors
As mentioned above, there are two types of CGRP inhibitors, gepants and monoclonal antibodies. Monoclonal antibodies are laboratory-produced molecules from a single clone of cells or cell line which consist of identical antibody molecules. For migraine prevention, monoclonal antibodies target either CGRP or the CGRP receptor. They are given by injection subcutaneously to avoid destruction in the stomach.
Currently, there are four FDA-approved monoclonal antibodies for the prevention of migraines, all of which were approved in the last 2 years: erenumab (Aimovig), fremanezumab (Ajovy), galcanezumab (Emgality), eptinezumab (Vyepti).
These drugs are given intravenously or by self-injection with a prefilled pen either once a month or quarterly. Side effects can include mild pain and/or swelling at the injection site, stuffy nose, constipation, and possible allergic reaction.
In addition, the gepant rimegepant is seeking approval for prevention as well as acute treatment of migraine. Another gepant, atogepant is in trials for migraine prevention.
Cefaly
Cefaly is a non-invasive transcutaneous neurostimulation device (TENS) that targets the trigeminal nerve. As explained by Riederer and colleagues, the device is “a constant current generator for a maximum skin impedance of 2.2 kOhms. In practice, the electrical impulses generated by the Cefaly headband are transmitted transcutaneously via a self-adhesive, supraorbital electrode to excite (trigger action potentials) on the supratrochlear and supraorbital branches of the ophthalmic nerve (V1) located under the skin of the forehead.”
The patient applies the device once a day (preferably in the evening) for 20 minutes. The current slowly increases over the course of the session and the patient begins to experience tingling or prickling of the forehead. The amount of current can be controlled to stabilize the intensity if the sensations become uncomfortable.
The FDA approved the use of Cefaly in November 2017 for the prevention of migraines in patients age 18 or older, saying that “the treatment has been shown to reduce the number of days during which people experience migraines.” Side effects include skin irritations, discomfort, sleepiness, dizziness, and pain at the site of application; however, these were present in less than 5% of patients and resolved quickly.
Sources: National Institute of Neurological Disorders and Stroke; and Deborah Tepper, MD, Headache: The Journal of Head and Face Pain, 2020.
Michele R. Berman, MD, and Mark S. Boguski, MD, PhD, are a wife and husband team of physicians who have trained and taught at some of the top medical schools in the country, including Harvard, Johns Hopkins, and Washington University in St. Louis. Their mission is both a journalistic and educational one: to report on common diseases affecting uncommon people and summarize the evidence-based medicine behind the headlines.
Source: MedicalNewsToday.com
