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.

Sumatriptan (Imitrex), rizatriptan (Maxalt) and the other 5 triptans work on serotonin receptors to stop a migraine attack. Many antidepressants, such as fluoxetine (Prozac), escitalopram (Lexapro), that belong to the SSRI family and venlafaxine (Effexor) and duloxetine (Cymbalta), that belong to the SNRI family of drugs also affect serotonin or its receptors. Because both triptans and antidepressants affect serotonin, it is understandable that there has been concern about the potential for serotonin-related side effects when these drugs are used together.

In 2006 the FDA released a warning, “Potentially Life-Threatening Serotonin Syndrome With Combined Use of SSRIs or SNRIs and Triptan Medications.” Fortunately, this is the case of “fake news”. My colleague in Houston, Dr. Randy Evans under the Freedom of Information Act, requested all the data that the FDA used to issue this warning. He published an article on his findings and concluded that “The data do not support prohibiting the use of triptans with SSRIs or SNRIs.”

A new study presented at the 59th Annual Scientific Meeting of the American Headache Society confirmed Dr. Evans’ conclusion. Dr. Yulia Orlova and her colleagues at the John R. Graham Headache Center at Brigham and Women’s Faulkner Hospital in Boston conducted a population-based study using information on more than 6.5 million patients. Over a 14-year period, about 19,000 were prescribed both triptans and SSRI or SNRI antidepressants. Between 4 and 7 patients (0.02% to 0.04%) developed serotonin syndrome.

In most cases serotonin syndrome is mild and consists of shivering, sweating, and diarrhea. Only very rarely it can be life-threatening with high body temperature, agitation, and seizures.

This is an important issue because migraine is 2-3 times more common in those suffering from depression and anxiety, while depression and anxiety are 2-3 times more common in people with migraines. This means that millions of people suffer from both conditions. Most experts agree that combining SSRIs and SNRIs with triptans is very safe.

A similar issue is the prohibition on mixing different triptans within 24 hours. There is not a slightest shred of clinical or scientific evidence for this contraindication. Nevertheless, the FDA-approved label has this warning for every triptan.