Update on Migraines

ONE OF MEDICINE’S enduring mysteries remains the underlying causes and a cure for debilitating migraines. Consequently, every physician has multiple patients suffering from migraine pain. The Migraine Research Foundation (MRF) reports 18 percent of adult American women suffer from migraines, as does 12 percent of the overall population. Migraines affect all ages and all ethnicities.

MRF contends that due to the severe pain and lost work time that results (90 percent of migraine sufferers can’t work normally during an episode), migraines are among the top-10 most-disabling diseases on the planet.¹ It also reports there are 1.2 million hospital visits per year in the United States for severe migraines.

Indeed, JMS Pearce, the British neurologist who coined the term “migraine,” pointed out some 30 percent of physicians may suffer from migraines. He wrote that the failure of medical science to determine the causes of or find a cure for migraines represents a “frustrated fascination” of those doctors who themselves suffer from them.²

What Are Migraines?

Migraines are differentiated from other headaches by these features:

• A pronounced throbbing from the pain;
• A heightened sensitivity to lights and sounds;
• The length of the attack (generally lasting from four to 72 hours);
• A pattern of recurrence;
• Pain localized on one side of the head;
• Nausea (with vomiting easing the pain somewhat)³ ; and
• A preceding aura marked by visions of bright lights or jagged lines.⁴

Not all patients exhibit all of these symptoms, and symptoms may vary from one migraine episode to the next in the same patient.

Women are three times more likely to develop migraines than men, and an estimated 28 million women in the United States suffer from migraines. Up to 10 percent of children have migraines, with boys slightly more likely than girls to have them until the onset of puberty. A child with one parent with migraines has a 50 percent chance of developing them at some point. And, the likelihood is 75 percent if both parents have migraines.¹

Migraines have been described since antiquity. Babylonian writings going back more than three millennia clearly describe the distinct symptoms of what we today refer to as migraines.⁵ By 1200 B.C., Egyptian doctors were suggesting applying pressure to the skull to help relieve the pain.⁶ About 400 B.C., Hippocrates also fully described migraines, including the aura, nausea and pain being confined to one side.²

The second-century A.D. Greek physician Claudius Galenus (better known as Galen of Pergamon) gave migraines their modern name when he referred to these unique headaches in Latin as hemi-crania (half cranium) — which was later anglicized into migraine. By the 17th century, migraines were well-accepted as a distinct category of headache.²

While migraines are not fatal, the so-far unknown underlying causes of migraines are associated with a higher risk of stroke and heart attack.⁷ It’s not necessarily a causal relationship, but the correlation seems fairly well-established. More recent research involving real-time brain scans and blood testing has helped further our understanding of the pathology of a migraine, if not yet illuminating its underlying causes.

There are other health risks associated with migraines: Depression is twice as prevalent in those patients with infrequent migraines, and four times as high in those with chronic migraines (four or more per month).⁸ Asthma and migraines are also highly correlated, although again, the exact cause and effect is not understood.⁹ The same is true with epilepsy.¹⁰

Causes of Migraines

While migraines are one of the most fully described of all medical afflictions, they remain among the least understood.

Researchers today believe the pain experienced during a migraine is caused by constriction of blood vessels in the brain — likely by changes in hormone levels, specifically serotonin and estrogen.¹¹ Advanced CT scans of patients during attacks have also indicated there is unusual electrical activity in the brain during a migraine.

Scientists do know some patients are more susceptible to having a migraine after certain events that may trigger its onset:³

• Hormonal changes (some women report they are more likely to experience a migraine at certain points in their menstrual cycle)
• Dietary changes (eating certain foods, skipping a meal or fasting can be associated with the onset of a migraine; some food additives — aspartame, monosodium glutamate — are also suspected triggers)
• Intense physical exertion
• Alcohol or medications
• Stress
• Changes in the weather
• Changes in sleep patterns¹¹

Although the specific causes of migraines are not yet understood, researchers believe there is likely a genetic susceptibility since the condition runs in families.³

Symptoms and Progression of Migraines

Medical literature describes a migraine as a progression, usually broken into three segments, following in chronological order: prodrome, attack and postdrome.

Many migraine patients notice indicators that a migraine is imminent. And, while these differ from patient to patient, they often include neck stiffness, food cravings, moodiness, constipation, increased thirst and increased yawning.¹² A minority of patients (perhaps 20 percent, according to some researchers) will experience an aura before the attack begins. Most patients who have auras describe them as visual: a bright light or distorted vision. Others have other sensory disturbances: a feeling of being touched, weakness and difficulty speaking clearly. These typically last from 20 minutes to an hour.

The migraine itself is generally (but not always) marked by severe pain on one or both sides of the head, marked by a throbbing sensation. It is often accompanied by sensitivity to light, sound or other senses (smell or touch). Nausea is common. Less frequently, patients experience blurred vision, light-headedness and sometimes even fainting. The attack, left untreated, can last from four hours to 72 hours. The postdrome, after the attack, can last for another 24 hours. Many patients report confusion or difficulty concentrating, dizziness, weakness, mood swings and sensitivity to light and sound.¹³

While most patients will see a drop in frequency and severity of migraines as they grow into their 60s and older, those with more frequent, painful migraines may actually see theirs become more frequent and severe — particularly without treatment.¹⁴ A minority of patients experience an increase in frequency of up to 15 or more migraines per month, at which point they are said to have chronic migraines.¹

Diagnosing Migraines

Since the term migraine is a descriptive condition (based on symptoms, not pathology), diagnosis is made most often by a discussion of the patient’s health history and symptoms. The patient may be referred to a neurologist to rule out other more serious conditions. An MRI or CT scan may be considered to eliminate the possibility of tumors, strokes, infections, parasites or bleeding. And, a spinal tap can help rule out infections or bleeding as their cause.¹⁵

Treating Migraines

Because the underlying causes of migraines remain undiscovered, treatment consists of alleviating symptoms and, possibly, preventing or lessening the severity of future attacks.

For mild migraines, over-the-counter pain relievers such as aspirin, ibuprofen and acetaminophen may be enough. However, overuse of these medications over time can lead to significant side effects such as ulcers and headaches.

More severe attacks may be treated with drugs designed specifically for migraines. One class of drugs, ergots (ergotamine and dihydroergotamine), is most effective in treating patients whose migraines occur frequently and typically last longer than 48 hours. These may be taken orally, by injection or via nasal inhaler.¹⁵ They work by narrowing blood vessels.¹⁶ Oftentimes, ergots are combined with caffeine to speed up their absorption into the bloodstream. Popular brand names of ergots combined with caffeine include Migergot and Cafergot. All of these can increase the nausea often associated with a migraine.

Another class of drugs used to treat migraines includes triptans, which also narrow blood vessels and block pain pathways. Triptans cannot be used in patients with coronary disease or a history of strokes. Popular brands include Imitrex (sumatriptan), Maxalt (rizatriptan), Axert (almotriptan), Amerge (naratriptan), Zomig (zolmitriptan), Frova (frovatriptan) and Relpax (eletriptan). Treximet is a popular combination of sumatriptan and naproxen sodium.¹⁵

For patients not eligible for either triptans or ergots, more powerful narcotics are sometimes prescribed. However, because of the side effects of opiates and opioids and the danger of addiction, it is advised these classes of drugs not be used long-term.

A drug normally prescribed to treat high blood pressure, Zestril (lisinopril), has been shown to lessen the length and severity of migraines in some patients.¹⁵

Due to the numerous side effects of all of the drugs used to relieve the symptoms of migraines, physicians usually work with their patients to create a treatment regimen that includes long-term prevention of future attacks.

Preventing Migraines

While modern painkillers can help ease migraine symptoms, many patients can avoid future migraines or suffer less severe attacks by following a preventive regimen. Unfortunately, there is no vaccine to give permanent protection, but there are a variety of prescriptions, exercises and lifestyle changes that can combine to lower the risk of future migraines. Those with frequent migraines (four or more a month) are encouraged to consider a prevention approach.¹⁵ Depending on the severity of the attacks and any other health issues, physicians may prescribe one of the following treatments:

Cefaly. An external neurostimulation device, the recently approved Cefaly is effective in some patients with episodic (nonchronic) migraines. Available only with a prescription, the device is worn with or without a band around the head with an electrode positioned over the forehead. Small electrical impulses are then sent through the skin, which seems to help many sufferers.¹⁷ While the manufacturer claims Cefaly also helps reduce the pain of ongoing attacks, the researchers cited in this footnote felt it was more effective at prevention than pain relief.

Erenumab. Earlier this year, the U.S. Food and Drug Administration (FDA) approved the first drug specifically designed and shown effective at preventing migraines. Sold under the brand name Aimovig, it works by blocking the calcitonin gene-related peptide (CGRP).⁴ The drug is self-administered monthly via injection.

Then, in September, FDA approved a second drug, Ajovy (fremanezumab), for migraine prevention. The monoclonal antibody that also works by blocking the CGRP is the only one of its kind to offer quarterly and monthly dosing options.¹⁸

Antidepressants. Because some antidepressants work by regulating levels of serotonin, they can also help prevent migraines. Amitriptyline, a tricyclic drug, is currently approved by FDA for use in preventing migraines. Other tricyclic antidepressants are sometimes used as they can have fewer side effects (sleepiness, constipation and weight gain are associated with Amitriptyline).¹⁵ However, the Mayo Clinic advises against using another class of antidepressants known as selective serotonin reuptake inhibitors since these can actually trigger a migraine or make the next one more painful.

Cardiovascular drugs. Two classes of drugs originally developed to treat high blood pressure have shown to be effective at preventing migraines in some patients. Three beta blockers are currently prescribed to prevent migraines: propranolol, metoprolol tartrate and timolol. When taking these, there is typically a several week period before improvement is noted. Patients who have an aura before a migraine may see improvement with verapamil (Calan and Verelan).¹⁵

Epilepsy drugs. Two antiseizure medications used in treating epilepsy have proved to reduce the frequency of future migraines in some patients. Valproate and topiramate have both been shown to be effective, but they also have significant side effects. Valproate should not be used by women who are or may become pregnant. It can cause nausea, tremor, weight gain, dizziness and loss of hair. Topiramate can lead to diarrhea, weight loss, nausea and memory issues.¹⁵

Botulinum toxin A. Sold under the brand name Botox, this derivative of the fatal bacterium Clostridium botulinum (the microbe that causes botulism) has been shown to be effective at reducing the frequency and pain of attacks in patients with chronic migraine.¹⁹

While the above medications and devices can help reduce the frequency and pain of future migraine attacks, most physicians will want to couple them with behavioral modification plans to further their effectiveness. These changes may include eating regularly scheduled meals, drinking plenty of liquids, getting regular rest and exercising consistently. Women whose attacks are tied to their menstrual cycle may be candidates for hormone therapy.⁴ Also, physicians will want to review a patient’s current maintenance prescriptions to see if any of those medications may worsen or even trigger migraine attacks.

Another part of prevention is learning to avoid, where possible, known triggers. To identify triggers specific to each patient, a migraine log may help. This entails a patient keeping a diary of daily events (meal times, sleep times, exercise, job stress, etc.) to try to isolate anything that may be triggering the migraines.²⁰

Ongoing Research

The lack of specific knowledge of the underlying cause of migraines isn’t for absence of research. Hundreds of studies are listed on ClinicalTrials.gov for migraine basic research, improved treatments and prevention.

One of the more interesting areas of study is the intersection between migraine and epilepsy. As noted above, several drugs used to treat epilepsy are also effective in treating migraines. And, it has been known for several years that epileptics are more likely than the general population to suffer from migraines, and migraine patients have a higher incidence of epilepsy. In fact, their symptoms can be so similar there is often misdiagnosis between the two conditions.¹⁰ Researchers are looking into whether both diseases could be caused by a common set of factors.

Other researchers are investigating a genetic link. Many migraine patients seem to have a common mutation in the TRESK gene that governs a critical potassium ion channel. This mutation may make brain cells more sensitive to pain.¹⁰

Researchers at the University of Michigan are using MRI and PET scans to map the brains of patients with migraines in hopes that other researchers will be able to use the data to gain additional insights into the physiology of migraines.²¹

As of this writing, Ionis Pharmaceuticals is recruiting subjects for a clinical trial of its IONIS-PKKRx, an RNA-targeted antisense drug designed to fight migraines by slowing production of prekallikrein, a necessary component of serine protease.²²

Biohaven Pharmaceuticals is testing Rimegepant that, like the already approved Aimovig, is in a class of calcitonin gene-related peptide blockers.²³

A professor at the University of Valencia in Spain is analyzing data from a study on whether a specific regimen of physical therapy involving stretching and exercise of certain neck muscles could help prevent or lessen the severity of future migraine attacks.²⁴

UCLA researchers are conducting a blind test to see if melatonin, a hormone associated with sleep cycles, may be effective at helping reduce migraines in adolescents.²⁵

And, while mechanical implants (similar in concept to the Cefaly device, but implanted under the skin like a pacemaker) have been under study since 1977, they have yet to come to market. However, research into these occipital nerve stimulation implants continues.²⁶

Looking Ahead

While researchers are ever closer to discovering the root causes of migraines and, hopefully, a permanent cure, they are not there yet. For now, physicians will continue to work with patients to alleviate pain and help prevent future attacks through a regimen of treatment and behavior modification.