A non-steroidal anti-inflammatory (NSAID) drug naproxen (Aleve) alone seems to be more effective than naproxen combined with sumatriptan (Treximet), according to a study by Dr. Roger Cady and his colleagues from Missouri, which was presented at the International Headache Congress in Boston.
This was a small study involving 39 patients who suffered with moderate to severe attacks of migraine. The researchers looked at possible effect of acute medications on frequency of headaches. As migraine frequency increases, so too can the risk of medication overuse, which leads to more headaches. On the other hand, frequent administration of acute medications may act both as an acute and prophylactic treatment. The patients in the study were 18 to 65 years of age, with frequent episodic migraine with or without aura, in Stage 2 migraine (3 to 8 headache days per month) or Stage 3 migraine (9 to 14 headache days per month). Patients were asked to treat their migraines with sumatriptan/naproxen (Group A) or naproxen alone (Group B) for 3 months. Patients in Group B had a statistically significant reduction in migraine headache days at month 3 compared to baseline. Group A also had a reduction of migraine headache days but this decrease did not reach statistical significance over baseline. In addition, subjects in Group B had a statistically significant reduction of migraine attacks at all three months of the study compared to baseline. A greater than 50% reduction in the number of migraine days at month 3 occurred in 43% (6/14) of subjects in Group B compared to 17% (3/18) of subjects in Group A. Sumatriptan/naproxen was statistically superior to naproxen at 2 hours in reducing the migraine headache severity. The amount of acute medication used decreased from baseline to months 1-3 for both groups. Both treatments were well tolerated. The authors concluded that naproxen provides headache relief at 2 hours and reduces frequency of headache days and migraine attacks. Despite both groups using similar quantities of naproxen, this was not seen in sumatriptan/naproxen group, but sumatriptan/naproxen is more effective as acute treatment at 2 hours in reducing headache severity but does not significantly reduce attack frequency or the number of headache days.
If confirmed by larger studies, this is a very surprising discovery because there is little evidence indicating that triptans, like sumatriptan in this study, cause increased frequency of migraines due to medication overuse. In fact, this study did not show that sumatriptan did that, but only that naproxen alone was better at preventing migraine headaches. We also know from Dr. Richard Lipton’s large studies that aspirin has a preventive effect and naproxen and other NSAIDs do not, although they do not worsen headaches either. The large and multi-decade Framingham study showed that 81 mg of aspirin taken daily also has small but statistically significant beneficial effect in preventing migraine headaches. As far as acute treatment of migraines, in a review by an independent organization, Cochrane Reviews, the extra strength dose of aspirin (1,000 mg) was shown to be as effective as 100 mg of sumatriptan.

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.