Calcium channel blockers, a family of drugs used to treat hypertension, are sometimes used for the prevention of migraine headaches. Anecdotal reports suggest that verapamil (Calan) can treat migraine with aura and other neurological symptoms. Double-blind trials of verapamil for the prevention of migraines have been unconvincing. Verapamil seems to be more effective for the prevention of cluster headaches, but even there the evidence is anecdotal.

Amlodipine (Norvasc) is another calcium channel blocker that has been reported to prevent migraine headaches, although reports include a very small number of patients. Since verapamil has been studied more extensively, it is usually used first. However, if verapamil works well but causes constipation, which can be severe, we usually switch to amlodipine. Amlodipine is less likely to cause constipation, but both drugs can cause swelling of the ankles, dizziness and other side effects.

Amitriptyline (Elavil) and other drugs in the family of tricyclic antidepressants have been proven to be very effective in the preventive treatment of migraine headaches and many other painful conditions.

Several double-blind, placebo-controlled trials have proven the utility of amitriptyline for the prevention of migraines. Amitriptyline is also an effective antidepressant, so it is perfect for patients with anxiety or depression. However, its effect on migraines and pain is proven to be independent of its effect on depression. That is, even in the absence of depression or anxiety, the drug prevents migraines and relieves pain.

Amitriptyline has an additional benefit for people with insomnia – it helps sleep. On the other hand, in some people this effect lasts too long and they feel sleepy or tired the next day. In such cases we try a different and less sedating tricyclic antidepressant, such as nortriptyline (Pamelor), desipramine (Norpramine), or protriptyline (Vivactil). This potential side effect is why we always start this and most other preventive drugs at a small dose, 10 or 25 mg nightly. Some people need only 25 mg, while other require 100 mg. This is often due to the variable absorption of the drugs. Fortunately, in case of amitriptyline a simple blood test can tell us how much of the drug is being absorbed. Some patients will achieve a good therapeutic level with 25 mg, while others need 100 or 150 mg. So, in the absence of side effects and lack of relief, the dose is slowly increased. When we get to 75 or 100 mg, blood test can provide guidance about the safety of further escalation of the dose.

High levels of tricyclic antidepressants can be dangerous, leading to arrhythmias – irregular heart rhythms. We usually obtain an electrocardiogram in the elderly and those at risk for heart disease before starting amitriptyline. Two other more common side effects of amitriptyline are constipation and dry mouth. In many patients constipation can be successfully managed with over-the-counter remedies, such as Senokot S or Miralax.

Acetylsalicylic acid, also known as aspirin, is a truly miracle drug. It is an excellent pain and fever-reducing medicine and prevents several types of cancer and cardiovascular disease.

Aspirin has been proven to be a very effective migraine medicine, especially if you take 3 regular strength (975 mg) or two extra strength tablets (1,000 mg). Aspirin works fast, but it can relieve a migraine even faster if it is taken in an effervescent form. These are more common in Europe, but in the US you can buy Alka-Seltzer, which contains aspirin and sodium bicarbonate. Sodium bicarbonate (baking soda)is an excellent antacid and reduces the risk of stomach irritation by aspirin.

Stomach irritation and peptic ulcers, along with bruising and bleeding are the main potential side effects of aspirin. These can be dangerous and even life-threatening, but are not likely to occur if aspirin is taken for an occasional migraine.

The risk of side effects goes up with taking aspirin daily, which has been proven to prevent migraines and to reduce the risk of episodic migraines becoming chronic. It definitely does not cause medication overuse headaches. Some studies suggest that as little as 81 mg a day is sufficient to prevent migraines, but 325 mg appears to be a more effective dose. Anecdotally, aspirin has been also reported to prevent migraine auras.

So, how does one decide whether to take aspirin daily. The decision is easier if you have another reason to take it, such as risk factors for coronary or cerebrovascular disease or family history of colorectal or another type of cancer. If you have a history of gastritis or peptic ulcers, bleeding disorder, or allergy to aspirin, the decision is also easy – don’t take it. If none of the above applies to you and you are in good general health, it may be worth trying, especially if you have failed to respond to Botox injections, beta blockers amd other preventive migraine drugs.

Amantadine (Symmetrel) is a medication that has U.S. Food and Drug Administration (FDA) approval for use both as an antiviral and an antiparkinsonian medication. However, it is not an effective antiviral drug and is no longer used for this indication. However, it is used for several “off label”, that is not FDA-approved indications, including fatigue of multiple sclerosis and migraines.

Amantadine has a blocking effect on the NMDA receptor, which is involved in pain messaging in the brain. Other NMDA receptor blockers are an Alzheimer’s drug memantine (Namenda) and magnesium. There are only two case reports – one of 14 patients (10 responded to amantadine) and another report of 3 patients with migraines responding to amantadine. So, this is one of the drugs we try after the failure of many other drugs.

Amantadine does have the advantage of having few side effects, but its efficacy in migraines is purely anecdotal.

Many migraine sufferers do not find acetaminophen (Tylenol) to be strong enough to treat migraine headaches and it does not have an official FDA approval for migraines (ibuprofen does). However, it is one of the most popular drugs for all kinds of pain, including migraines. And, in fact, double-blind placebo controlled trials have proven that acetaminophen does relieve pain and associated symptoms of migraine headaches.

One such study published in 2000 in the Archives of Internal Medicine by Dr. R. Lipton and his colleagues compared 1,000 mg of acetaminophen with placebo in 351 migraine sufferers. After 2 hours, 58% in the acetaminophen group and 39% in the placebo group reported relief. Twice as many had no pain at all after 2 hours in the acetaminophen group compared to placebo – 22% vs 11%. No side effects were reported in either group.

This study does not prove that acetaminophen is as strong as prescription drugs, such as sumatriptan (Imitrex), because the authors excluded patients with very severe attacks – those who needed to lie down and those who had vomiting more than 20% of the time.

So, while acetaminophen can help some patients with milder migraines, it can be a useful adjunct to a prescription drug, such as sumatriptan, especially if ibuprofen, naproxen, and other NSAIDs are contraindicated or cause upset stomach or other side effects. Acetaminophen is better tolerated than NSAIDs, but it should not be used at a high dose for long periods of time because it can cause liver damage.

Almotriptan (Axert) belongs to the family of triptans, which are, by far, the most effective drugs for the acute treatment of migraine headaches.

The first drug in this category, sumatriptan (Imitrex) was introduced in 1992 as an injection. Sumatriptan injection remains the most effective treatment – it works for 80% of migraine sufferers. The tablets of sumatriptan and other triptans are a bit less effective, but still provide good relief for over 60% of patients. For some, combining a triptan with 400 mg of ibuprofen (Advil, Motrin) or 500 mg of naproxen (Aleve, Naprosyn, Anaprox) makes it much more effective.

Almotriptan is one of the five relatively fast-acting triptans. The other four are sumatriptan, rizatriptan (Maxalt), zolmitriptan (Zomig), and eletriptan (Relpax). Naratriptan (Amerge) and especially frovatriptan (Frova) take longer to begin helping, but their effect tends to last longer.

In Europe, many triptans are sold without a prescription, which indicates that these are very safe drugs. There is no evidence that triptans cause medication overuse headaches (unlike caffeine and opioid/narcotoc drugs). See my post on daily use of triptans and a recent article debunking the myth of medication overuse headaches.

This is the first in a 100-part series of blogs on various migraine drugs. Yes, we do use that many drugs to treat migraines, although only a handful are FDA-approved for migraines. Many of these drugs are in the same family, but they are all somewhat different from each other.

Acetazolamide (Diamox) is a diuretic (water pill), which is used to treat mountain sickness. Unlike other diuretics, it is somewhat selective in removing extra fluid from the brain and the lungs, rather than equally from all parts of the body.

Migraine sufferers whose migraines are triggered by traveling to high altitudes can sometimes prevent these migraines by taking acetazolamide the day before their ascent and then throughout their stay at high altitude. A handful of my patients continued to take acetazolamide even after they returned to the sea level because they found it to be effective in preventing all of their migraines. These patients tended to have barometric pressure changes as their main migraine trigger. For people who get only occasional weather-related headaches, taking acetazolamide daily is not necessary. However, they can often prevent an attack by taking the drug the day barometric pressure drops and for as long as the pressure fluctuates.

To avoid having to constantly watch the weather forecast, a couple of apps can send you a warning whenever barometric pressure drops (it usually takes a drop of 20 millibars of pressure to trigger a migraine). One such free app is MigraineX.

Interestingly, people who live at high altitudes tend to have more migraines than those living aa the sea level.

Acetazolamide is also used to treat headaches due to increased intracranial pressure (pressure inside the skull).

Acetazolamide is available in 125 mg, 250 mg, and an extended release, 500 mg tablets. The usual starting dose is 250 mg once a day. Potential side effects include tingling of your face and extremities, dizziness, altered taste (carbonated beverages have a very unpleasant taste), and with long-term daily use, kidney stones.