Thank you to Amaal Starling, MD and Robert Nicholson, PhD, FAHS for their contributions to this spotlight!
Is it Migraine – Or Something Else?
Migraine is not just a headache. It’s a different disorder with different symptoms and different treatment approaches compared to ordinary headaches. The American Migraine Foundation estimates that at least 36 million Americans get migraine, but it’s probably more because many people with migraine do not get a formal diagnosis or treatment from a migraine specialist.
So, how can you tell if your head pain is actually a migraine? If you answer yes to two or more of these features below, it may be migraine and you should think about seeing a doctor.
- Your head pain is severe and intense—hard to endure, may be unbearable.
- Your head pain causes throbbing sensations, often on one side of your head.
- You experience nausea and vomiting, and sensitivity to light, noise and odors.
- Your head pain gets worse with physical activity or any movement.
- Your head pain is severe enough to make you miss work or other activities or keep you from being at your best when you do those activities.
- It lasts a long time, anywhere from 4 hours to several days.
Migraine characteristics like those above make it different from other types of headache.
Some people may have migraine with aura. The most common type of aura is visual (flashes of light, blind spots, shapes or bright spots). Some people with aura will have blurred vision or actually lose their vision. Typically, aura occurs before the head pain begins. Most people with migraine, however, do not experience auras.
Based on frequency, patients may suffer from Chronic Migraine (CM) or episodic migraine (EM). People with CM experience greater than 15 days per month with headache. People with EM have fewer days with headache per month. Migraine occurs more often in women than men. Migraine attacks can be triggered by many factors. Common triggers include stress, certain foods or skipping meals, sleeping too much or too little, changes in weather or barometric pressure, hormonal changes in women, concussions and traumatic brain injuries. There is evidence that migraine is hereditary or genetic since it often runs in families.
If any of this sounds like you and the head pain you experience, please make an appointment to see a doctor or migraine specialist. (For more information about finding someone to diagnose and treat you, click here.)
A Brief (Sad) History of Treatments for Migraine
Migraine has been plaguing people since the beginning of recorded time. Famous artists, writers, philosophers, political figures, athletes, actors, singers, models, and millions of ordinary Americans have struggled with the pain of migraine.
The quest for cures and relief also has been intense over the centuries and many treatments have been advanced—some weird, some odd, some even brutal: hot irons, bloodletting, inserting garlic into an incision made into the temple, applying opium and vinegar solutions to the skull, and surgery.
Virtually all these treatments proved useless. In the 1930s, someone tried ergotamine, which constricts blood vessels in the brain and provides some people with relief. Others tried using drugs and approaches developed for other illnesses for migraine with varying success. In the early 1990s, triptans were introduced. They were the first, and still only, class of drugs developed especially for migraine treatment. They have been the mainstay for relief for many people ever since. Unfortunately, they don’t work for everyone and are designed to treat a migraine—not keep a person from getting them. Despite the millions of people from all walks of life who struggle with the pain of migraine, there remains only one class of drugs designed just for migraine.
Over the years, the search for a cure for migraine has eluded researchers. For a more detailed history of the search for an effective migraine treatment and a cure, click here.
A section of this Spotlight is devoted to the current state of migraine research and promising drugs by clicking here.
What’s Holding Up the Search for a Cure for Migraine?
Money. It’s that simple. And that difficult.
There’s not much spent in this country on migraine compared to similarly disabling conditions. The National Institutes of Health allocates about $20 million a year for migraine research—that comes out to about 55 cents for each person with migraine. Given the costs to business, society, and to the people who endure migraine, about $260 million would be more fitting.
There may be many reasons migraine gets pushed aside. Maybe it’s because it’s usually not fatal, or it’s episodic, or maybe because people who have it tend not to take to the streets to advocate for it. Migraine and the people with migraine have been trivialized and stigmatized in our culture.
To make things worse, industry (drug companies) don’t put migraine at the top of their research and development priorities because they don’t see a quick return on their investment.
Physicians and other healthcare professionals who potentially could diagnose and treat migraine in their patients don’t always recognize migraine or distinguish it from other headache types. If they do, they are not always well versed in treatment options. Often, the subject of migraine or head pain never comes up in a checkup visit.
It is an invisible chronic illness. Unless someone is in the midst of an attack, you can’t tell they have migraine. They frequently stay home during an attack, often in a dark bedroom under the sheets. When they emerge, many are so relieved to not be in terrible pain that they simply pick up their lives where they left them and move on. But they know how bad it is, and their families certainly know.
If you’d like to read more on this, click here.
To bring migraine out of the shadows and shine a light on it, the American Migraine Foundation launched the 36 Million Migraine Campaign last year to help raise the funding priority for migraine in the United States and draw people’s attention to the tremendous burden and pain migraine brings.
We believe that if there is any chance of conquering migraine, people with migraine and their friends and families will lead the way.
Please join us by visiting this page on our website: https://americanmigrainefoundation.org/give/
Finding Out If It’s Migraine
There’s really only one way to know: find a migraine specialist who can diagnose your head pain. Some people consult their primary care doctor who may or may not know much about migraine symptoms and diagnosis. So if possible, try to find someone who specializes in migraine.
Many academic medical institutions have migraine or headache clinics that work together with the American Headache Society. You can also follow this link from the American Migraine Foundation’s Find a Doctor.
Many people with migraine don’t go to a doctor at all and try to cope with the pain and disruption in their lives without medical help. This is not only unnecessary—t can be harmful.
When should you go to someone who can help? Here are some guidelines from American Headache Society Board Member Deborah I. Friedman, MD, MPH, FAHS, and who is also Director, Headache and Facial Pain Program at the University of Texas Southwestern Medical Center in Dallas.
It’s time when …
- Your head pain is moderate to severe and causes nausea and vomiting. You also experience sensitivity to light and/or noise.
- Your head pain causes you to miss work, family activities and keeps you from doing what you want to do.
- If you have migraines once a week or more.
- You think that you are handling it on your own, but you are taking pain medication—including over-the-counter medication—more than two times a week for head pain.
- Your friends and family identify you by your headaches
Getting the Most Out of Your Doctor’s Appointment
You’ve found a headache doctor and made an appointment. Now how will you and your doctor determine that you have migraine? There’s no blood test, ultrasound, or MRI that will tell your doctor if your head pain is migraine. The only real way for your doctor to know is for you and him or her to talk about the specifics of your head pain (how often, how bad, and associated symptoms), how you have handled the pain until now, family history of migraine, current and previous treatments including over-the-counter medications, and how your head pain limits your quality of life.
You won’t have a lot of time with the doctor, especially if you’re seeing a primary care physician, so go prepared. Think about these questions, write down the answers if you can, and take them with you to the appointment.
About the head pain:
- How long have you had head pain?
- How many times in a week/month do these attacks occur?
- How severe are they (mild, moderate, severe)?
- How long do they last?
- How disabling are they (how much do they keep you from doing activities or keep you from being at your best when doing activities)?
- Do you get any warning that an attack is about to happen (such as zigzag lines or dark spot in your vision)?
- Do you throw up or feel nauseated?
- Do odors, noise or light make them feel worse?
- Have you ever had a brain CT or MRI?
- When was it done?
- What were the results?
- Have you ever been treated for headache or migraine by a doctor in the past?
- If so, what medications or other therapies did you try (list them if you can or get them from your health record)?
- What dosages?
- How effective were they?
- How long did you take them?
- What side effects did you have?
- Have you ever heard that or do you know of a close relative that (parent, grandparent, sibling, child) had bad head pain?
- Does anyone else in your family experience the same disabling head pain?
It may also be useful if you took the Migraine Disability Assessment (MIDAS) test before your doctor visit. Click here.
There are eight questions that can help your doctor understand the disability caused by your head pain.
Migraine Relief: The Current Landscape and What Lies Beyond
Migraine-specific treatment options are limited. However, many medications developed for other conditions can be helpful for people with migraine. Medications for depression, seizures, and high blood pressure have been found to be helpful for migraine. Unfortunately, many of these medications do not work for all migraine sufferers. In addition, they will often have side effects or contraindications for use in the presence of other medical conditions. Please discuss the currently available treatment options with your migraine specialist. Although not migraine-specific, they can be helpful for some people. Further research is needed to advance the treatment of migraine.
There’s no cure, but there are treatments that can reduce migraine frequency, severity, and stop a migraine attack before it gets worse.
Here are general categories of treatment and what they are intended to do:
- Preventive treatments—These are designed to reduce headache frequency and severity. These treatment options can be pharmacologic, such as medications or procedures, and non-pharmacologic, such as treatment devices, lifestyle changes, trigger avoidance, behavioral therapy, or physical therapy. These preventive treatment options work in about 40% of patients and typically reduce migraine frequency by at least 50%.
- There is only one FDA approved treatment for Chronic Migraine (attacks occur 15 or more times a month, and that is onabotulinumtoxinA (Botox.) For more on Botox, see https://headachejournal.onlinelibrary.wiley.com/ in an article by Emily D. Mauser and Noah L. Rosen, MD in the American Headache Society’s journal Headache.
- Acute or as needed treatments—these are taken when you are experiencing a migraine attack and are designed to stop it before it gets worse. These include over-the-counter pain relievers, prescription medications, or treatment devices.
For a fuller discussion of treatments, visit these pages on AmericanMigraineFoundation.org:
There is hope on the horizon. In recent years, migraine science has made great advances to understand brain chemistry, pain pathways, and migraine genetics, which may lead researchers deeper into the search for cures.
Among those that excite migraine scientists is work with the calcitonin gene related peptide (CGRP), which seems to block transmission of pain and stop migraine attacks before they get started. Several pharmaceutical companies are now involved in the study of drugs based on the actions of CGRP.
For more on CGRP, please read the article by David W. Dodick MD of the Mayo Clinic and Chairman of the American Migraine Foundation’s 36 Million Migraine Campaign. https://americanmigrainefoundation.org/resource-library/promising-new-science/
You may also want to read more about other interesting work in the search for a cure. The American Headache Society’s professional journal is packed with information for those who want to dig deeper. Visit http://www.headachejournal.org/view/0/searchResults.html?q=promising+research to see more.
What’s in the “Pipeline”? Experimental and Recently Approved Migraine Therapies
Stephen D. Silberstein, MD
Director, Jefferson Headache Center
Thomas Jefferson Medical Center
1. CGRP (calcitonin gene-related peptide) Antagonists
- Four companies have CGRP-focused monoclonal antibodies in development to treat episodic and chronic migraine (migraine headaches that occur 15 or more days a month and affect 3.2 million Americans). CGRP binds to the CGRP receptor and is involved in migraine pain. CGRP levels increase during a migraine attack and often remain elevated in the blood stream in chronic migraine. Three companies are developing monoclonal antibodies directed against CGRP, and one company (Amgen) is developing a monoclonal antibody directed against the CGRP receptor complex.
- Alder Biopharmaceuticals is developing ALD403, a monoclonal antibody to CGRP.
- They have completed a controlled proof of concept study published in Lancet Neurology. Sixty percent of patients had a 50% response (Placebo was 33%), and 16% had a 100% response rate (Placebo was 0%)
- Amgen is developing AA32, a monoclonal antibody directed against the CGRP receptor complex. They have completed preliminary studies.
- Eli Lilly is developing LY2951742, a monoclonal antibody to CGRP. They have completed a Phase II randomized, double-blind, placebo controlled study published in Lancet Neurology. Thirty-one percent of patients receiving the drug had a 100% reduction in headache days. Drug was originally developed by Artaeus Pharmaceuticals, which was bought by Lilly.
- TEVA Pharmaceuticals is developing LBR-101, a monoclonal antibody to CGRP. Has conducted Phase IIB trials. They have completed preliminary studies. TEVA acquired the rights to LBR-101 when it bought Labrys Pharmaceuticals.
2. Lasmiditan (5HT1F agonist)
- CoLucid Pharmaceuticals is developing Lasmiditan for treatment of acute migraine (i.e., migraine attacks). The company has just received funding to start Phase III clinical trials. Lasmiditan is a member of a drug class called “diptans.” These drugs penetrate the central nervous system and selectively target 5HT1F receptors in the trigeminal nerve pathway (the trigeminal nerve is a cranial nerve responsible for sensation in the face. It is believed to play a key role in migraine attacks).
- Six clinical studies, including a Phase IIB trial, have been successfully completed. This is the only 5HT1F agonist being developed. Triptans (eg, sumatriptan, zolimitriptan, eletriptans, etc.) are 5HT1B 5HT1D receptor agonists. In addition, some are 5HT1F receptor agonists. 5HT1B receptors are located on blood vessels and are responsible for cardiac contraindications to triptans.
3. TI-001 (Oxytocin Nasal Spray)
- Trigemina Inc. is conducting a Phase II study of TI-001 for the treatment of chronic migraine. Oxytocin is a peptide that reduces migraine-related inflammation. An injectable form of oxytocin has been available for more than 60 years, and nasal oxytocin (in a lower dosage than TI-001) is available in Europe.
These are devices that stimulate peripheral nerves or the brain itself in order to modulate headache. Some are already on the market for treating epilepsy, depression, and headache. Others are being developed specifically to treat migraine. Categories are:
Transcranial magnetic stimulation (TMS)
- eNeura has an FDA-approved device (SpringTMS) to relieve the headache pain of migraine with aura. It’s a non-invasive, portable, battery-powered device that patients hold to the back of their head as soon as they notice symptoms. It delivers a quick, single, magnetic pulse to the back of the head.
- This results in stimulation of the occipital cortex, which may reduce brain hyperactivity associated with migraine. It is now undergoing post-market, open-label studies that suggest it decreases migraine attacks.
Vagus nerve stimulation (VNS)
- electroCore Medical makes a non-invasive VNS device called “GammaCore.” It’s a small handheld device in which patients can adjust the intensity themselves. It is used to deliver two, 90-second electrical stimulations to the neck over the vagus nerve.
- It may work by sending signals to the brain that reduce levels of glutamate, which is a neurotransmitter in the trigeminal nerve that sends pain signals to the brain, resulting in headache. GammaCore has had positive results in studies for chronic migraine and cluster headache.
Supraorbital transcutaneous stimulation
- This FDA-approved Cefaly device (made by Cefaly), is worn around the front of the head. It has an adhesive patch that is attached to the electrode that’s positioned mid-forehead. It delivers mini-electrical impulses to nerve endings of the trigeminal nerve (a nerve that has a branch ending in the forehead). This produces a tingling effect, which, when regularly repeated, has been shown to reduce the number of migraine attacks.
Occipital Nerve Stimulation
- This involves surgically putting electrodes around nerves in the occipital region. The electrodes are connected to an implanted neurostimulation device. Neurostimulation is already in use for treating other types of pain. The devices have been shown to reduce the frequency and intensity of migraine attacks in chronic migraine patients for whom medical therapies don’t work.
- Electrodes are implanted under the skin and over the occipital nerves, and attached via leads (thin wires) to a battery that is implanted in the chest. The physician programs the battery (using a handheld programmer) to deliver electrical charges when migraine attacks are about to begin. St. Jude Medical and Medtronic make neurostimulation devices that are under study for chronic migraine.
Sphenopalatine Ganglion Stimulation
- The sphenopalatine ganglion (SPG) is a nerve bundle located deep in the face. Autonomic Technologies, Inc. (ATI) developed the Pulsante™ SPG Microstimulator System to provide on-demand SPG stimulation to relieve the acute severe pain of cluster headache by blocking the nerve signals that are thought to be responsible for the pain and autonomic symptoms associated with cluster headache. Cluster headache is a highly disabling headache disorder characterized by intense stabbing pain in the area of one eye, often accompanied by swelling, tears and nasal congestion. Attacks, each lasting 15 to 180 minutes, can occur multiple times a day.
- The device is inserted through a small incision in the upper gum above the second molar and positioned at the sphenopalatine ganglion (SPG) nerve bundle. Patients control their own stimulation treatment, as needed, by turning on the Remote Controller and placing it on the cheek over the inserted device. It is currently in clinical trials in the US.
A variety of behavioral techniques may be used alone or to augment the effects of pharmacologic treatment. Behavioral treatments; involve learning skills designed to train the body to be less “on edge” (e.g.:, relaxation training, biofeedback, and cognitive-behavioral therapy with a focus on managing stress) and skills designed to promote a healthy lifestyle, including getting adequate sleep, not skipping meals, regular exercise, and being aware of food, beverages, or other substances that may trigger or exacerbate a migraine attack.
The U.S. Headache Consortium (Silberstein, 2000) made the following recommendations pertaining to behavioral treatment for migraine:
-  relaxation training, thermal biofeedback combined with relaxation training, electromyography biofeedback, and cognitive behavioral therapy may be considered as treatment options for preventing migraine (Grade A Evidence); and
-  behavioral therapy may be combined with preventive drug therapy to achieve added clinical improvement for migraine (Grade B Evidence) (Campbell et al. 1999; http://www.aan.com/).
Relaxation training, biofeedback, and cognitive-behavioral therapy are specific techniques that can be effective for many patients. Each of them has a similar goal: to train the patient to have the skills to not be excessively aroused (that is, less stressed, tense, on edge) physically and mentally. Each of them provides the patient with skills to rapidly respond to life situations that can provoke stress, anxiety, or anger. They also provide the patient a skill they can use daily to help keep their body not being as stressed, tense, on edge in general. This helps the patient be less susceptible to getting a migraine.
These techniques are often used in combination, but take a slightly different approach to training the skill. In relaxation training, the patient learns to recognize how their body (especially muscle areas) feel when they are tensed versus relaxed. The patient then learns to breathe in a way that helps promote less tense muscles and learns when to recognize tension in daily life and apply relaxation techniques.
In biofeedback, the patient learns, by video and/or audio feedback, to recognize the difference in how their body feels when it is excessively aroused (that is, stressed, tense, on edge) versus when they are not. Thermal feedback of skin temperature (hand warming), and electromyography feedback (electrical activity from muscles of the scalp, neck, and/or upper body), are the most commonly employed biofeedback modalities The person then learns how to control their body’s internal arousal system (called the autonomic system) and applies those skills to be less stressed, tense, on edge in daily life. In cognitive-behavioral therapy, the patient learns to recognize stressful situations and learns skills to respond to the situation differently and over time, change how they view situations so they don’t provoke stress, anxiety, or anger. Other behavioral techniques, including yoga, meditation, and other psychological therapies In particular, yoga and meditation can increase vagal nerve activity, an important part of physical and emotional health.
There are no treatments in development targeting specific populations, however, there are existing treatments targeted to Menstrual Migraine (MM)
If severe MM cannot be controlled by standard acute and preventive treatment, hormonal therapy may be indicated. Successful hormonal or hormonal modulation therapy of MM has been reported with estrogens (alone or combined with progesterone or testosterone, combined OCs, synthetic androgens, estrogen modulators and antagonists). Progesterone is not effective in the treatment of headache or the symptoms of PMS. Extended-duration contraceptive regimens have been shown to be of more benefit than traditional regimens.