The Migraine Brain

by Bernstein, Carolyn; McArdle, Elaine

If you’re hesitant about taking a drug every day to stop your migraines, consider whether you’d feel the same way if your disease were diabetes instead of migraines. You may not be taking your migraine seriously enough as an illness. Migraine deserves as much attention and respect as any other disease.

  One of my patients had a MIDAS score of over 100 when she first came to see me—one of the highest scores I’ve ever seen. She was extremely disabled, with migraines almost every day. Under my supervision, she began taking a preventive drug, topiramate, and, within three months, she experienced a 30-percent reduction in migraines. Today, she continues to get severe headaches pretty frequently, but what an improvement! I’m continuing to work with her to see if we can reduce her migraines even further with biofeedback.

  Another patient started on a course of preventive medication and—for the first time in ten years—she experienced a full week where she had no headaches. At the end of the week, her headaches returned. But they were less frequent and much less severe.

  Questions About Preventive Drugs

  Some choices available for preventing migraines include beta blockers, anticonvulsants, and antidepressants. Each drug has a specific mechanism by which it works in your brain. Some, like beta blockers, decrease spasms in blood vessels, which may be one way that migraines cause pain. Some, like seizure medications, stabilize membranes of nerve cells. Antidepressants may make certain neurotransmitters more available to brain cells. With some medications, we just don’t know precisely how they work to prevent migraines. The latest research shows that different kinds of preventive drugs may share the common characteristics of reducing your susceptibility to cortical spreading depression (see Ch. 2), which we now believe is the key factor in migraine.

  Are they safe? All prescription drugs are approved for use in humans by the FDA, so, in general, they are safe. However, you should be an educated consumer of any drug you take. Just because it is FDA-approved doesn’t mean it is safe for everyone. Some drugs are unsafe for people with certain health problems, and some have contraindications with other drugs you may be using.

  What does “off-label” mean? An off-label drug is one that was designed to treat a specific disease but that also works well in treating another for which it was not intended or approved. For example, beta blockers and channel blockers were developed to prevent heart disease but also are used to treat migraine. Botox injections are a cosmetic treatment, but a side effect is that they may reduce headache frequency in some patients. Antidepressants and antiseizure drugs also work really well for some migraineurs. It isn’t illegal or dangerous to use a drug “off-label,” which means only that the drug hasn’t yet been submitted to the FDA for approval to treat migraine.

  If your doctor prescribes an off-label medication, it doesn’t mean that you have heart problems, are depressed, or have a seizure disorder. She should explain that distinction to you. It’s your right to ask you doctor as many questions as you want about the drugs she is prescribing.

  When do I take the medication? Your doctor should tell you what time of day to take your preventive medicine. Lots of drugs work best if you take them at night. Also, if they can make you sleepy, you don’t want to take them before heading off to work or driving a car.

  Some preventives are once-a-day drugs, while others are taken more frequently. I try to avoid prescribing migraine meds more than twice a day because it’s too easy to forget the mid-day dose.

  To help my patients remember to take their twice-a-day meds, I tell them to put the pills near their toothbrush, since they brush their teeth in the morning and evening. But don’t leave your pills out if you have little children who might get into them.

  How do I take them? Most migraine medications can be taken either on an empty stomach or with food. And for most people, it’s okay to have the occasional alcoholic drink—unless alcohol is one of your migraine triggers. Many antiseizure medications include a warning on the label advising you to avoid alcohol, but this warning applies to seizure patients, not migraine patients. For migraineurs, drinking alcohol while taking this medication is probably not a problem, but be sure to ask your doctor.

  What about interactions with other drugs? Drug interactions are a valid health concern. Some drugs can become toxic when combined with another drug; others simply stop working. If you are taking any kind of medication—even over-the-counter drugs like aspirin or ibuprofen—you must tell your headache specialist before he prescribes a migraine medication. Your health could be at stake. As an added precaution, you can also ask your pharmacist about drug interactions when you drop off your prescription.

  Be sure to tell your doctor if you have any allergies. If you have a sulfa allergy, for instance, you can’t use some migraine drugs, such as topiramate.

  What about a migraine “cocktail”? You may be prescribed more than one migraine medication, since some people need several drugs in order to get relief. The term for this is “polypharmacy.”

  With preventive medications—or any drug—it’s important to be very careful when you mix medications. More than one can be helpful, but some people take three or four different migraine meds, with no better result than if they were taking just one. One patient, referred to me by another doctor, was on eleven different migraine medications—and she was still getting terrible migraines. This simply is not healthy. I gradually detoxed her off all the medications and we started a new treatment plan from scratch. She began taking a medication that she hadn’t tried before—and she got good results.

  If your doctor prescribes more than one migraine med, make sure you are told what each one is supposed to do and what results to expect. And use your headache journal and the MIDAS scale (see Ch. 7) to chart whether these meds are reducing your migraines.

  What about side effects? You should ask your doctor this question every time you get a prescription. It’s the mark of a concerned consumer. And the truth is, every drug has side effects, even the most commonly used, seemingly innocent drugs, like aspirin or caffeine. Some potential side effects are very rare, but you should know what they are before you start taking a medication.

  The more information your doctor has about your medical health, the better. Let’s say you had an ulcer in the past. NSAIDs like ibuprofen and aspirin may not be safe for you because they can irritate the lining of your stomach and may cause further ulcers and bleeding. Some drugs worsen depression, others drop your blood pressure. Some make you gain weight, others can affect your memory.

  Your doctor should review all potential side effects and warn you about any serious toxicity. She should explain why she thinks the medication is safe and appropriate for you. Ask your doctor what her experience has been with this medication. Has she treated a lot of patients with it? What did they experience? Topiramate, for example, causes weight loss—but my patients were the ones to alert me to the fact that it makes soda and soft drinks taste metallic. I’ve since warned other patients who tried it that they might experience this side effect.

  Sometimes, doctors just run out of options and try things not so commonly used for migraines. This may be okay—but your doctor should explain everything she is doing and talk about the safety and usefulness of her plan. And remember, it’s always your right to say no. You shouldn’t try any migraine treatments you aren’t comfortable with.

  One thing you don’t have to worry about with preventives is rebound headaches. Preventives don’t cause rebounds.

  How long will I take the medication? We never know how long a particular migraine drug will continue to be effective for you. Migraines often change in severity, duration, and symptoms, so you need regular reviews of your medication. You and your headache doctor should have an ongoing relationship that continues past the initial visit.

  My patients complete the MIDAS scale at our first visit, before starting any medication, to give a baseline of how disabled they are by migraine. Then, they repeat the MIDAS scale to give us a measure of whether their headaches are improving.


  Make sure you and your doctor have a plan for monitoring your reaction to the drug and that you schedule return appointments for evaluation. I like the “rule of three months,” where a patient tries out a medication for three months before we decide whether it’s working or we need to try something else. But don’t wait three months if you’re having a problem! Call your doctor immediately if you have a negative reaction to the drug or some other serious issue.

  It’s likely you can be weaned off a preventive med at some point in the future. How long that will take varies with each patient. If your headaches come back, you will most likely want to get back on a preventive.

  Types of Preventive Drugs

  Different classes of drugs for migraine prevention work in different ways and have different side effects. Your doctor should explain why she has chosen a particular drug for you.

  Blood pressure medicines This category of drugs—which includes beta blockers and channel blockers—works on blood vessels. One theory of why migraines occur is that blood vessels may have “vasospasms.” These medicines may help dilate smooth muscles in the blood vessel walls and relax the blood vessels.

  Here are some blood-pressure drugs your doctor may consider, depending on your health needs:

  Inderol is a beta blocker, an older drug for hypertension (high blood pressure) that relaxes the blood vessels. It may be a good choice for you if you also have high blood pressure in addition to migraines, or if you have focal neurologic changes with your migraines, like numbness or weakness.

  Side effects to know about:

  can make you feel slow, tired, and decrease your energy

  drops your pulse and heart rate, which may make you dizzy or light-headed

  can affect sexual function in men (the ability to have an erection)

  is not a safe drug for someone with asthma.

  Inderal has an FDA-approved indication for migraine prevention. But it may take months to work. There may be other beta blockers that are appropriate for you.

  Verapamil (Calan) is a calcium channel blocker that affects blood vessels by changing the cell membrane’s permeability to certain chemicals. This may be a good choice for you if you:

  can’t take a beta blocker (if you have asthma, for example, which is a contraindication)

  have menstrual migraines

  have orgasm or exercise-induced migraines

  have high blood pressure (because it lowers blood pressure).

  Side effects to know about:

  can make you feel slow or tired

  causes constipation in some patients

  can slow your heart rate and decrease your heart’s ability to contract.

  Seizure medication. The second category of migraine prevention drugs is the anticonvulsants or seizure medications. These drugs stabilize the membranes of nerve cells. They prevent or alter certain channels (openings) in the outer layer of the cell and prevent depolarization (firing) of the neurons. Often, these drugs work quickly and are easy to tolerate. Of course, if you also have seizures, these drugs may treat both illnesses together.

  Valproic acid (Depakote) was the first seizure drug to get FDA approval for migraine prevention and is very effective for many people. It works on sodium channels in the cell membrane, which for some people may not work properly and thus trigger migraines. It may be a good choice for you if you have frequent migraines and are not on a lot of other medications.

  Side effects to know about:

  can cause weight gain

  may interfere with birth control pills

  may cause tremors (in high doses)

  can cause hair loss

  absolutely cannot be taken if there is any chance of your becoming pregnant

  Topiramate (Topamax) is a newer drug that, like valproic acid, is FDA-approved for migraine prevention. Although topiramate was designed as a seizure drug, when its ability to reduce migraine pain was noted, further studies were conducted and it was approved as a migraine drug for a certain population of patients with frequent, disabling migraines.

  It’s not yet known precisely how topiramate works, but it is effective as a sodium channel blocker and a GABA-receptor agonist, which means it helps another neurotransmitter, GABA, to work more effectively. It has several other mechanisms by which it may work as well.

  It may be a good choice for you if you are concerned about weight gain (on average, users lose 3.8 percent of body weight), if you don’t take a lot of other medications, or if you have tried some of the older migraine medicines without success.

  Side effects to know about:

  Can cause kidney stones, especially in people who have already had them

  can cause acute myopia/narrow-angle closure in glaucoma

  can interfere with oral contraceptives, at higher doses

  can cause grogginess and aphasia (trouble with finding words), especially at higher doses.

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  Warning—Do Not Use Antidepressants Along with Triptans There is a potential danger to people who use triptans and also use certain commonly prescribed antidepressants called SSRIs or SNRIs. Taking these drugs together can lead to a potentially fatal condition called “serotonin syndrome.” Symptoms include drowsiness, muscle contractions and rigidity, sweating, heart racing, hallucinations, confusion, nausea, vomiting, and diarrhea.

  Be sure to tell your doctor about all drugs you are using. Be especially sure to tell her if you are taking antidepressants before she prescribes a triptan for your migraines.

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  Antidepressants. Antidepressants, like seizure medications, can be very helpful to some migraine patients. There are many different kinds of antidepressants, some in use for many years as well as newer ones coming on the market all the time, and some may be choices for patients who are also depressed because one medicine may treats both illnesses. Even if you’re not depressed, your doctor may recommend one of these medicines for you.

  Amitriptyline (Elavil) is an older drug for migraine prevention. When prescribed in smaller doses, it’s often very helpful for migraine sufferers who may also have sleep disturbances and, perhaps, a low-grade depression that contributes to the migraines. We aren’t sure exactly how it works for migraine, but it may have some indirect effect on the body’s opioid receptors, which helps with natural painkillers.

  It may be a good choice for you if you:

  are also depressed (although, for many people, it’s not as effective in treating depression as the newer antidepressants)

  have trouble with sleep (it helps initiate and maintain sleep)

  have severe daily headaches

  have other types of pain, such as low back pain, as well as migraines

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  Warning—Migraine Drugs You Cannot Use If You Are Pregnant or Nursing

  Be sure to tell your doctor if you are pregnant or planning to get pregnant or if you are nursing. There are many migraine drugs you should not take.

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  Side effects to know about:

  can be dangerous for people with some types of heart disease

  can make you groggy during the day

  can cause urinary retention

  can make your mouth dry

  SSRIs—selective serotonin reuptake inhibitors—are newer drugs for depression that are also being used for many different types of chronic pain as well as migraines, although they don’t have a specific indication for this use.

  Botulinum toxin (Botox) is best known as a cosmetic treatment that helps with wrinkles, although it was developed for neurological illnesses such as muscle spasm and neck stiffness. It is not yet FDA-approved for migraine prevention, but studies are going on now, and your doctor may know of some experimental protocols in which you can participate.

  WARNING: If you are using Botox for any reason, seek immediate medical care if you have trouble breathing or swallowing, begin slurring your speech, or have muscle weakness.

  Abortive Drugs

  If you have fou
r or fewer migraines a month, an abortive drug may be the choice for you. These drugs abort or halt the migraine so it doesn’t get any worse, and often make it go away entirely. You must take the abortive drug as soon as you can feel a migraine coming. Otherwise, your migraine may get too far along, the abortive will fail, and you may end up with a full-blown migraine. (At that point, your recourse is to use a rescue drug, which we’ll discuss below.)

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  Special Caution—Rebound Headaches

  All of the abortive drugs we describe in this section come with a serious caution: If you take too many of them, you can cause a rebound headache (also called a medication-overuse headache), which is very difficult to treat. See Ch. 1.

  If your medication—prescription or over-the-counter—stops working, do not increase the dosage without talking to your doctor. You may very well end up with a rebound headache and compound your migraine problem.

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