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.

Zomig (zolmitriptan) is the fourth triptan (out of seven) to become available in a generic form. This spells big relief for migraine sufferers who rely on this drug. Only tablets and orally disintegrating tablets (ZMT) will become available, not the nasal spray. Nasal spray offers faster relief and for some patients it is as fast as sumatriptan injection (Imitrex, Sumavel, Alsuma). It may take another 6 months for the price to drop significantly from the current $30 to $45 a pill because at this point only four companies are coming out with a generic version. There are about 10 manufacturers making generic Imitrex. Generic sumatriptan (Imitrex) is now available for $3 a pill, while the other two generics, Maxalt (rizatriptan) and Amerge (naratriptan) are still more expensive.

One caveat with the generics is that the quality sometimes is not as good as that of the brand. Of approximately 10 generic sumatriptan versions, my patients have found that 2 are very ineffective. One of these two manufacturers which is based in India (Ranbaxy), recently paid $500 million fine to the FDA for improper manufacturing, storing and testing of drugs. Many generic manufacturers are based in India and most of them produce good quality products. One of them is Dr. Reddy’s Laboratories. Of the four generic manufacturers of Zomig two are based in India (Glenmark and Zydus), one in Taiwan (Impax) and one is based in the US (Mylan) but also has many manufacturing plants in India. An Israeli company Teva, the largest manufacturer of generics in the world is known for their high quality products and it also has plants in many countries, including India.

Once you find a product that works, stick with that generic manufacturer even if you have to switch pharmacy chains since the entire chain usually carries the same generic. The law requires that the name of the manufacturer is printed on the medicine bottle your receive from the pharmacy, so it is easy to find out who the manufacturer is.

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Pregnant women are admonished not to take any medications while pregnant. Fortunately, two out of three women stop having migraines during pregnancy, especially during the second and third trimester. Unfortunately, one third of women continue having migraines and in some they get worse. Tylenol (acetaminophen), which is deemed to be the safest pain medicine in pregnancy is also the weakest pain killer and does nothing to relieve the agony of a migraine attack. Many obstetricians say that they are also “comfortable” giving drugs containing butalbital (a barbiturate) and caffeine along with acetaminophen (Fioricet) because these drugs have been around for many years. However, barbiturates are really not good for the developing brain while regular intake of caffeine can cause worsening of migraine headaches. Narcotic (opioid) analgesics are not exactly healthy either. Not taking any medications is also harmful to the mother and the fetus because severe pain causes serious distress to both and vomiting, which often accompanies migraines, can cause dehydration. Not treating migraine attacks may also lead to chronic migraines with pain present continuously. So, what is a pregnant woman to do?
At the recent annual meeting of the American Congress of Obstetricians and Gynecologists several doctors expressed their preference for the use of triptans in pregnant women. Sumatriptan (Imitrex) was first introduced 20 years ago and a registry of women who took sumatriptan during pregnancy suggests that this is a safe drug. Pregnancy registry for rizatriptan (Maxalt), which is the second triptan to come to the market 15 years ago, also suggests that it is a safe drug. Of course, it cannot be said that these drugs are proven to be safe for pregnant women because some yet undetected risk may still be present. However, compared to the alternatives and considering that triptans are much more effective, it is logical to recommend their use in pregnancy.
Besides treating an acute attack with triptans we always recommend preventive measures, such as magnesium supplementation (400 mg, on top of what is in a prenatal vitamin, which is usually only 100 mg), biofeedback, regular sleep, and exercise.
Preventive drugs that can cause major problems in the fetus and are contraindicated in pregnancy include divalproex (Depakote) and topiramate (Topamax). On the other hand, Botox is probably a safe preventive treatment in pregnant women suffering from chronic migraine headaches.

Art credit: JulieMauskop.com

Preventive drugs for migraine headaches help less than half of the patients they are given to. There is no significant difference in effectiveness in these drugs. They reduce frequency of attacks by 50 percent, according to a review published in the recent issue of the Journal of General Internal Medicine.

Dr. Shamliyan from the University of Minnesota in Minneapolis and her colleagues conducted a literature review to identify high quality clinical trials of preventive drugs versus placebo.

Based on 215 published trials, the researchers found that all FDA-approved drugs, including topiramate (Topamax), divalproex (Depakote), timolol (Blocadren), propranolol (Inderal) and off-label medicines metoprolol (Toprol), atenolol (Tenormin), nadolol (Corgard), captopril (Capoten) and lisinopril (Zestril); and candesartan (Atacand) were effective in reducing monthly migraine frequency by 50 percent or more in 20% to 40% of patients. Topiramate, other off-label antiepileptics, and antidepressants had higher levels of side effects and were more likely to be stopped by patients because of side effects. While there were no significant differences in benefits between approved drugs, candesartan and other blood pressure drugs were the most effective and had fewest side effects for the prevention of episodic migraines.

The authors also noted that there was no evidence for long-term effects of drug treatments (that is trials lasting more than three months).

This review confirms my bias in favor of Botox injections over drugs. Botox helps not only 70% of chronic migraine patients, but in my anecdotal (but involving thousands of patients) experience it is equally effective for the prevention of frequent episodic migraines.

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The release of a generic substitute of the branded drug Imitrex (sumatriptan) has dramatically reduced the cost and improved the access to this uniquely effective migraine drug. The generic sumatriptan was released four years ago and now the price of one tablet is down to about $3 from over $20. The cost of two other generic triptans, Amerge (naratriptan) and Maxalt (rizatriptan) has remained very high, but it is expected to drop as more companies begin making generic copies. However, generics are not always the exact copies of the original branded drug that we expect them to be. In my previous post in 2009 I mentioned a study that showed that the generic Topamax (topiramate) does not work as well as the brand for some patients. I have also seen this with sumatriptan – my patients tell me that some generics do not work very well or at all. Out of about 10 generics of sumatriptan, I would guess that two are of poor quality. Once you find a generic that works for you, try to stick with the same generic manufacturer. The name of the manufacturer is printed on the bottle the pharmacy gives you. If one pharmacy does not have your generic, try another one. Here is a part of an email I just received from a patient (she gave me permission to share it with you):
“Just wanted to share with you that my pharmacy filled my maxalt melt prescription with yet another generic brand yesterday, which I found very unpleasant.
Previously the generic refills I’d gotten were from a company called PAR. The PAR pills resembled the original MAXALT melts in style of packaging (foil packets in plastic case) in taste and most important in melt-ability (never timed it but it always seemed to dissolve within 5 to 10 seconds–basically immediate dissolve)
But yesterday’s refill was from Mylan. These melts came in a regular prescription bottle of pills. I called the pharmacy after they were delivered thinking they accidentally gave me non-melts. They checked and told me, no, these were melts, just from a different company. They explained that this company (Mylan) packages them like any other pill (in bottles).
When I took the pill last night it felt like what i imagine it would feel like if you took a chewable vitamin and then waited for it to disintegrate in your mouth. It took minutes to “melt”, instead of seconds, and a grainy feeling remained even after that. it also made my upper palate sore, and tasted bad.
Today I called my pharmacist to double check that this was a melt and they checked again and it is. Luckily they were good enough to switch the rest of the prescription to the PAR generic brand. They also told me they would no longer carry the ones from Mylan. (They did say the Mylan generic is cheaper, though, so not sure how this will work out in the future.)”

Cambia (diclofenac) is a prescription anti-inflammatory drug (NSAID) which is approved by the FDA for the treatment of migraine headaches. It is sold as a licorice-tasting powder that has to be dissolved in water before being ingested. This drug belongs to the same family as Advil or Motrin (ibuprofen), Aleve (naproxen), and prescription drugs, such as Relafen (nabumetone), Celebrex (celecoxib), and other. One of the drugs in this category, Viox (rofecoxib) was taken off the market because it increased the risk of heart attacks and strokes. A recent study published in an online medical journal, PLOS Medicine and translated into lay language in an NPR article indicates that diclofenac is as dangerous as Vioxx in causing heart attacks and strokes. The study also indicates that diclofenac unfortunately is one of the most popular NSAIDs in the world. It is probably safe to take Cambia a few times a month to treat migraine headaches, however, it should be avoided by people with other risk factors for heart disease and strokes. These risk factors include migraine with aura, high blood pressure, high cholesterol, diabetes, smoking, oral contraceptives, family history of heart disease, and other. Aspirin (in Migralex and other products), on the other hand, is the only NSAID that has been shown to prevent strokes, heart attacks, and several forms of cancer.

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Daily and prolonged intake of high doses of triptan medications (sumatriptan, or Imitrex, rizatriptan, or Maxalt, eletriptan, or Relpax and 4 others) has been shown to be safe in at least three clinical reports. I also have a few patients who have good control of their headaches and no side effects after many years of taking high doses of triptans daily. (I am not suggesting that it is healthy to take any medicine daily for years, but some people have no other choice because without this treatment they are disabled). A report just published in The Journal of Clinical Pharmacy and Therapeutics describes a patient who also was taking high doses of triptans daily (zolmitriptan or Zomig and frovatriptan or Frova tablets and sumatriptan injections), but who developed severe depression on two occasions when the triptans were stopped suddenly. The first bout of depression was very difficult to treat despite trials of several antidepressant drugs (amitriptyline, or Elavil, mirtazapine, or Remeron, and duloxetine, or Cymbalta, with addition of quetiapine, or Seroquel). All these antidepressants work through the serotonin system. His second bout of depression responded very well to bupropion (Wellbutrin), an antidepressant that works on norepinephrine and dopamine, rather than serotonin. This report suggests that while it may be safe to take triptans daily for a long time, they can affect the serotonin mechanisms in the brain and that they should never be stopped suddenly. Another important lesson is that if depression does develop after stopping daily triptans, the preferred drug may be bupropion.

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Migraine headaches that occur at around the time of menstrual period tend to be more severe and more difficult to treat. Analysis of studies that involved 187 women with menstrual migraines who treated at least one of their attacks with frovatriptan (Frova) and one with another triptan showed that frovatriptan was more effective. While all triptans were equally effective in providing pain relief at 2 and 4 hours, rate of headache recurrence was significantly lower for frovatriptan. After 24 hours, 11% of women who took frovatriptan had a recurrence of their headache, but with other triptans 24% had their migraine come back. After 48 hours, the numbers were 15% for frovatriptan and 26% for other triptans. One caveat is that all of these studies were funded by the maker of frovatriptan.

I see many patients who tell me that “I’ve tried every migraine drug” and seek me out to explore non-drug approaches, such as herbs, supplements, Botox, acupuncture and other. I always try to avoid using medications (and have written books on non-drug approaches), but some patients do best with a combination of medications and non-drug approaches. So, when someone tells me that they’ve tried “every drug”, I tell them that I’ve never seen such a person because there are so many drugs that we use to treat headaches. For example, they might’ve tried a blood pressure medication, but we have many different anti-hypertensive drugs and they work in different ways. One type of blood pressure medication may work when another does not. Also, if one drug caused side effects, another in the same or different category may not.
Here is a brief description of blood pressure medications that are used for the prophylactic treatment of headaches. The first medication approved by the FDA for the prevention of migraine headaches was propranolol (inderal) (methysergide or Sansert was approved earlier, but it is no longer available in the US). Propranolol was originally developed for the treatment of hypertension and then accidentally was found to help migraine headaches as well. A second beta blocker, timolol (Blocadren) was also tested, was found to work well and it also received FDA approval. Other beta blockers, such as atenolol (Tenormin), labetalol (Normodyne), and nebivolol (Bystolic) were also shown to be effective. Nebivolol tends to have fewer side effect, but it is not yet available in a generic form, so it can be relatively expensive. Propranolol is available in a slow release form (Inderal LA) which can be taken once a day, while regular propranolol goes in and out of the body quickly and needs to be taken two or three times a day. Atenolol and nebivolol produce effect that lasts all day, so they can be taken once a day. Atenolol is very inexpensive and I always remind patients to ask the pharmacist about the price without insurance because the insurance co-pay can be higher than the out-of-pocket cost of the drug. Most pharmacists will not volunteer this information.
Because beta blockers worked for migraines other blood pressure medications were also tested. Calcium channel blockers, such as verapamil (Calan), amlodipine (Norvasc), diltiazem (Cardizem), and other do not seem to be as effective as beta blockers. High doses of verapamil are very effective for the prevention of cluster headaches.
Another category of blood pressure medications, ACE (angiotensin converting enzyme) inhibitors, such as lisinopril (Zestril, Prinivil), enalapril (Vasotec) and other do help probably as well as beta blockers. These medications sometimes cause cough or other side effects and can be substituted by similar drugs in the category of ACE receptor blockers (ARBs). ARBs do not cause cough and may have fewer other side effects. Drugs in this group that were studied for the prevention of migraine headaches include olmesartan (Benicar), losartan (Cozaar), and candesartan (Atacand).

Steroid injections are routinely used at our Center for the treatment of cluster headaches and occipital neuralgia. I just received a call from a concerned patient with cluster headaches who recently received an occipital nerve block with methylprednisolone acetate (Depo-Medrol), the same drug that caused fungal meningitis in almost 200 patients, of whom 14 died. His cluster headaches stopped after the injection and he had no symptoms of meningitis, but understandably he was still concerned. All of the patients who contracted meningitis were given epidural injections which are given for low back or neck pain with medicine deposited near the meninges or soft covering that envelopes the spinal cord. All of them received a tainted product manufactured by a compounding pharmacy, which was not licensed to mass produce such medications. Their product was significantly cheaper than the same medicine produced by the largest pharmaceutical company in the world, Pfizer. We have never used any other products except for the one made by Pfizer. I an addition to methylprednisolone (Depo-Medrol) some doctors use a different steroid, triamcinolone, which is manufactured by Brystol Myers Squibb under the name Kenalog. Whenever you receive a steroid injection for back pain, joint inflammation, cluster headaches, or any other indication, ask the doctor if the steroid you are going to receive was manufactured by a major pharmaceutical company. In case of epidural steroid injections, you should also question if these injections are really necessary because they have never been proven to be effective in the first place and even pure untainted products have been associated with spinal cord damage and other serious side effects.
Epidural steroid injection:

Steroid medications can be very effective for migraine headaches that fail to respond to other medications. Steroids, such as prednisone, dexamethasone, methylprednisolone have many potential serious side effects if taken for a long time. We know about these long-term side effects from patients with asthma, arthritis, lupus and other conditions who have take steroids daily for months and even years. However, these medications are relatively safe if taken for only a few days. If a severe headache does not respond to Migralex, sumatriptan, (Imitrex), or other medications, I prescribe a two-day course of dexamethasone. The usual dose is 8 mg daily for two days. Other doctors prescribe a six-day course of methylprednisolone (Medrol Dosepak). However, if a headache completely resolves after two days, it seems unnecessary to continue this medication for the full six days. In the office, we also give intravenous dexamethasone which provides faster relief than tablets. Another indication for steroids is for cluster headaches. A ten-day course of prednisone (starting with 100 mg and reducing by 10 mg every day) can sometimes stop the entire cluster period. Unfortunately, for some cluster headache sufferers headaches return as soon as the dose of prednisone is lowered. If no other preventive medication, such as verapamil, lithium, topiramate (Topamax) or divalproex (Depakote) work, some patients with severe attacks are willing to accept the risk of long-term side effects of steroids. Some of these side effects are weight gain, diabetes, stomach ulcers, glaucoma, high blood pressure, and osteoporosis.