We should not complain about our health care system. People in such advanced European countries as Netherlands have it much worse. I just saw a 27-year-old Dutch woman with chronic migraines who has been coming to see me for Botox injections every three months for the past 3 years. Three years ago she was told by her neurologist to quit law school because even if she was able to graduate, her migraines will prevent her from being able to hold a job. She is graduating from law school this June. Her doctors also told her not to take sumatriptan (called Imigran in Europe and Imitrex in the US) more than once or twice a week and take only aspirin on other days. This approach made her unable to function on the five days when she did not take sumatriptan, but even with sumatriptan her headaches were still disabling. Botox injections produced a significant improvement in the severity of her attacks, although not in the frequency. However, now sumatriptan provides complete relief and she can function normally. She tried to find a way to get Botox injections in Holland and offered to pay the doctor. He was not able to do it because medicine is socialized in Holland and he could not accept payment for procedures not covered by the health service. She turned to the government and offered to reimburse the health service for Botox, but they also refused. She is fortunate in that she is able to afford to come to New York every three months and buy as much sumatriptan as she needs to function normally.
Things are not much better in the UK and other European countries. The UK approved the use of Botox for chronic migraine before it was approved in the US. However, their national health service also refuses to pay for it. My Italian colleagues have told me that as a society they’ve decided that Botox was too expensive to be used for the treatment of migraines, despite the evidence that it works. I should note that just like many other drugs, Botox is significantly cheaper in Europe than in the US.

Muscle relaxants can be surprisingly effective for the prophylactic treatment of migraine headaches. It is surprising because migraine is a brain disorder and not a disorder of muscles. However, studies have shown that during a migraine attack muscles are in fact very contracted and that is probably why people find some relief by rubbing their temples and the back of the head. We also thought that Botox works by relaxing these tight muscles, but it turned out that it also works on nerve endings. Muscle relaxants also do more than just relax muscles – they actually work on brain mechanisms of migraines. Not all muscle relaxants help migraines and the most evidence exists for tizanindine (Zanaflex). A double-blind study was done by Dr. Alvin Lake and his colleagues and it showed very good efficacy and few side effects. The target dose was 8 mg three times a day, but the average dose was 18 mg a day. The main side effect of this drug is sedation, but otherwise it is fairly benign. Baclofen (Lioresal) is another muscle relaxant that has been subjected to a double-blind study and was found to be effective for the prevention of migraine headaches. The drug was also given three times a day with a total dose ranging from 15 to 40 mg a day. The main side effect of baclofen is also sedation. Other muscle relaxants, such as metaxalone (Skelaxin), cyclobenzaprine (Flexeril), clonazepam (Klonopin), and other have helped some patients, but there are no scientific studies to prove their efficacy in migraine.

How much sumatriptan (or another triptan) is too much is not clear. The initial FDA-approved daily dose of oral sumatriptan (Imitrex) for the treatment of an acute migraine was up to three 100 mg tablets. Several years later the maximum daily dose was reduced to 2 100 mg tablets a day, to be taken at least 2 hours apart. There was no scientific or safety reason for the reduction of the dose. Two other triptans, rizatriptan (Maxalt) and frovatriptan (Frova) are still allowed to be taken three times a day. The maximum dose of eletriptan (Relpax) is 2 40 mg tablets, however, in Europe it is 2 80 mg tablets. Some doctors are very strict in adhering to these arbitrary limits. Some patients will tell me that they always need to repeat the dose of a triptan 2 hours after the first dose. It makes sense to have them take a double dose at once and the results can be much better – the headache will go away and will not return. It is true that the higher the dose the more side effects you can expect. In patients who are sensitive to drugs or weight less than 100 lbs, it is prudent to try half of the usually dose and in everyone else the standard dose should be used at first. If the standard dose is not fully effective, another triptan can be tried, but if none provide sufficient relief and do not cause side effects I first recommend combining the standard dose of a triptan (100 mg of sumatriptan, 10 mg of rizatriptan, 40 mg of eletriptan, and so on) with an anti-inflammatory medication, such as Migralex (aspirin/magnesium), naproxen (Aleve), or ibuprofen (Advil). Only if this combination also fails would I suggest doubling the standard dose of a triptan.
What about the maximum dose of a triptan to be taken in a month? The initial studies of sumatriptan were conducted in patients who had 2 to 6 migraines a month and when the drug was approved by the FDA no monthly limit was imposed. However, the manufacturer packaged sumatriptan tablets in a blister pack of 9 tablets. This became the unofficial limit, even though no studies were ever conducted to examine the safety and efficacy of frequent sumatriptan (or any other triptan) use. Many doctors, including headache specialists believe that taking any abortive medication, including triptans too frequently will make headaches worse (so-called medication overuse headaches). We do have good scientific evidence showing that caffeine in fact can worsen headaches by causing caffeine withdrawal, or rebound headaches. People who drink large amounts of caffeine know that if they stop their caffeine intake they will develop a headache. In patients prone to headaches, as little as 2 cups of coffee, tea, or soda can worsen their headaches. We also have some evidence that barbiturates, such as butalbital (Fioricet, Fiorinal, Esgic) and opioid analgesics, such as codeine, oxycodone (Percocet), hydrocodone (Vicodin) and other can cause worsening of headaches if taken more than once a week. However, we have no evidence that triptans or NSAIDS, or non-steroidal anti-inflammatory drugs (Advil, Aleve, Motrin, Relafen, Voltaren, etc) cause worsening of headaches if taken frequently. Aspirin (such as in Migralex) in fact may prevent worsening of migraines.
I do discourage frequent use of triptans, which usually indicates poor control of migraines. Most patients with frequent migraine attacks are better off with preventive therapies, such as aerobic exercise, biofeedback, magnesium, CoQ10, Botox injections, or sometimes even preventive drugs. A common barrier to the frequent use of triptans is the insurance company. Many insurers have been reducing their monthly coverage of triptans from 9 to 12 down to 4 or 6, while increasing co-pays. This is clearly done not out of any safety concerns, but to save money.
With all of the above said, I do have about two dozen (out of thousands) patients who require very frequent or daily intake of triptans. These patients have gone through many of the preventive treatments listed above, including Botox, and they are still having daily headaches, or what we call chronic migraines. I usually try to have them stop triptans for several weeks to see if they improve with NSAIDs and prophylactic treatments, but most do not. These patients have very good control of their migraines, have no side effects, and can function normally. I am concerned about the potential cardiac side effects of these drugs, which are well documented. If a patient has some risk factors for heart disease (post-menopausal, high cholesterol, hypertension, diabetes, smoking, obesity, family history, etc), a stress test should be obtained.
What prompted this post was an article in the latest issue of journal Headache, which reports on a 49-year-old woman with 18 years of chronic cluster headaches. Injectable sumatriptan is the only treatment approved for cluster headaches. This woman has been injecting herself with 6 mg of sumatriptan anywhere from 2 to 37 times every day (on average, 20 times) for 15 years. She had no side effects or negative effects on her heart and there was no decline in the efficacy of sumatriptan over time. She failed several abortive and preventive medications. Other doctors have published articles describing patients taking triptans very frequently without loss of efficacy or side effects, but this patient has the most frequent and prolonged use ever reported.

Pregnant women who take NSAIDs such as naproxen (Aleve), ibuprofen (Advil), diclofenac (Volaren, Cambia), celecoxib (Celebrex), and other are two and a half times more likely to have a miscarriage. This is a finding of Canadian researchers who examined the records of 4,705 women who had a miscarriage. Surprisingly, they did not find that the risk was higher with a higher dose of NSAIDs. NSAIDs are particularly dangerous in the third trimester, when they can also cause heart problems in the fetus. Instead of NSAIDs pregnant women can try taking acetaminophen (Tylenol), which unfortunately is not a very effective pain killer. Narcotic or opioid drugs, such as codeine, Vicodin and similar drugs are not safe in pregnancy either, but can be used occasionally, although they are not very effective for migraine headaches. Triptans, such as sumatriptan (Imitrex), rizatriptan (Maxalt), eletriptan (Relpax) and other while not approved for pregnant women, may be safer and much more effective than either NSAIDs or narcotics. If a pregnant woman has frequent headaches, prevention with intravenous magnesium, biofeedback, and Botox injections should be tried before resorting to daily preventive drugs.

Risk of irregular heart beat, heart attacks, and death increases in people taking NSAIDs, such as ibuprofen (Advil), naproxen (Aleve), diclofenac (Cambia, Voltaren, Cataflam), and celecoxib (Celebrex). The risk with these drugs in people who suffer from hypertension and heart failure is well-known, but two recent large studies provide additional information on this risk. A study in the British Medical Journal that reported on 32,602 patients with atrial fibrillation suggested that patient who developed atrial fibrillation (dangerous irregular heart beat, which is often called A fib) were more likely to have been taking NSAIDs (but not aspirin) when this heart condition occurred. Another study conducted by Danish doctors and published in the journal Circulation looked at 83,677 patients who suffered a heart attack. They discovered that taking an NSAID drug (but again, not aspirin) for as little as one week increased the risk of having a second heart attack and dying by 45%. Taking NSAIDs for three months increased the risk by 55%. It is particularly unfortunate for heart patients who suffer from migraine headaches because they are also not allowed to take migraine drugs, such as sumatriptan (Imitrex), rizatriptan (Maxalt), and other triptans. This leaves them with aspirin (or Migralex – a combination of aspirin with magnesium, developed by Dr. Mauskop) and pain drugs that can make headaches worse (Fioricet, codeine, Vicodin, and other). Another option for these patients is to use preventive treatments, such as magnesium (which is also very beneficial for heart conditions), CoQ10, biofeedback, Botox injections, acupuncture, and as a last resort, preventive medications.

Aspirin is the first-line treatment for migraine and tension-type headaches regardless of headache intensity, according to a report published by three leading headache experts (from Austria, Germany, and Norway) in the journal Headache. Some headache expert advise using a prescription drug such as sumatriptan (Imitrex) or another triptan (Maxalt, Zomig, Relpax, etc) from the outset if the headache is severe and to use aspirin or similar drugs when the headache is less severe. However, this review of published data from large clinical trials suggests that aspirin works equally well for both moderate and severe headaches. This is true for both migraine and tension-type headaches. The six migraine trials reviewed included 2,079 patients (1165 with severe and 914 with moderate attacks) treated with 1,000 mg of aspirin and one tension-type headache trial had 325 patients (180 with moderate and 145 with severe attacks) treated with 500 mg and 1,000 mg of aspirin. Prior studies have also shown that 1,000 mg of aspirin is as effective as 100 mg of sumatriptan in the treatment of migraine headaches and aspirin had fewer side effects. Disclosure: I have patented and developed Migralex, an over-the-counter drug which contains (in 2 tablets) 1,000 mg of aspirin and 150 mg of magnesium.

Topiramate (Topamax) increases the risk of birth defects, such as cleft lip and palate, warned the Food and Drug Administration (FDA). Topiramate is an epilepsy drug which is also approved for the preventive treatment of migraine headaches. It is a very popular drug, in part because it can cause weight loss in some patients. In clinical trials only half of migraine patients who started taking this drug remained on it for more than a few months because it was ineffective for some and caused intolerable side effects in others. One of the main side effects which makes people stop taking this drug is difficulty speaking and thinking. Topiramate is also known to cause kidney stones and the initial data suggested that less than 1% of patients taking it developed kidney stones. However, a recent report suggested that up to 20% of people taking topiramate for a period of two years will develop kidney stones. Half of the patients who developed kidney stones were not aware of it. Kidneys stones not only can be very painful, but in severe cases can impair kidney function.
These two newly discovered dangers are additional reasons to avoid taking topiramate and if possible, to avoid taking any medications. While we do prescribe many medications, including topiramate, we always begin with life style modification (diet, sleep, exercise), biofeedback or meditation, magnesium, CoQ10, and other supplements, acupuncture, and Botox injections.