Branded triptan medications are extremely expensive with one pill of Relpax or Frova costing $30 – $40. Fortunately, Imitrex, Maxalt, Amerge, and Zomig tablets are available in a generic form. However, even the generic version of Amerge is $3 to $4 a pill, although generic Imitrex and Maxalt can be found for $2. Unfortunately, some patients respond only to Relpax, Frova or Zomig nasal spray, which insurance companies tend not to pay for. Other people need medications that are not available in the US, such as domperidone, an excellent drug for nausea or flunarizine, a calcium channel blocker for the preventive treatment of migraine (not such an excellent drug because of its side effects).

Some patients who need a branded product or one not available in the US buy drugs from online Canadian pharmacies. But how do you know if the pharmacy is legitimate? Some sites that claim being a Canadian pharmacy in fact are not Canadian and the drugs they sell are fakes. One way to find a legitimate Canadian pharmacy is to check if it is certified by the Canadian International Pharmacy Association. You can also check if the pharmacy is certified by the PharmacyChecker.com and is listed on their free website.

When buying locally, you can find a pharmacy with the cheapest price for a specific drug by going to GoodRx.com. But do not assume that if a pharmacy offers the lowest price on one drug, its prices on other drugs will also be the lowest.

Art credit: JulieMauskop.com

The approval of the lower dose Sumavel device is a good opportunity to again remind migraine sufferers about the benefits of injectable sumatriptan. Many doctors do not even mention to their patients that sumatriptan is available in an injection that is easy to self-administer. Obviously, if a tablet of sumatriptan (Imitrex) or another triptan works quickly and prevents the headache from becoming disabling, there is no need for an injection. However, when the tablet does not work fast or well enough or if nausea makes it difficult to swallow tablets, injection can be a life saver. Injections of sumatriptan are available in a variety of devices. One of them is Sumavel, an injection without a needle. This device propels the medicine through the skin as a very thin jet of fluid. It is perfect for those with needle phobia. It also has the advantage of not having to worry about the proper disposal of needles. Having a choice of a 4 mg or a 6 mg dose allows patients with frequent cluster headaches to take 3 4 mg doses in 24 hours (maximum recommended dose is 12 mg). The 4 mg dose is also useful for people who get side effects from 6 mg, since 4 mg may be sufficiently effective without causing side effects.

Topamax (topiramate) has been reported to cause inability to sweat which can lead to hyperthermia or overheating. At first, this condition was reported as a rare complication, but a study of 173 children showed that 22 of them or more than 10% developed this side effect. The ability to sweat returns when the drug is stopped. Sweating allows the body to coll off and loss of this mechanism can be dangerous in hot weather or during vigorous exercise. Those who take Topamax should speak to their doctor if they notice reduced sweating.

Topiramate is an effective drug which the FDA approved for the prevention of migraine headaches as well as epilepsy and mood disorders. However, in large clinical trials only half of the patients put on this drug for the treatment of migraines stayed on it. The other half either did not obtain relief of their migraines or developed side effects. One of the most common side effects is impairment of cognitive functions – people can’t remember names, can’t come up with the right words, or as some have told me they feel stupid. Other people become very tired from Topamax because they develop metabolic acidosis – their bodies become too acidic. Long-term side effect of kidney stones was also thought to be rare when the drug was introduced, but subsequent studies showed that up to 20% of patients develop kidney stones.

The full extent of side effects of any new drug does not become apparent until years after its introduction. This does not mean that we can afford to wait for years before trying new drugs since some of the patients who come to our center with migraine headaches do not respond to the available treatments. What we can do is monitor these patients very closely and stop the drug as soon as possible.

At the New York Headache Center we always try to avoid using medications and use alternative (i.e. non-drug) therapies first. We often succeed, but unfortunately, many of our patients do end up taking some drugs. However, when choosing among many medications, we start with the ones that are least likely to harm. Depakote (sodium valproate) is an effective drug for the treatment of epilepsy, mood disorders, and migraines. While we do prescribe Depakote to our patients, it has never been our first, second, or third choice because we already know that it can cause liver problems and fetal malformations. A recent study published in Neurology adds another reason to avoid this medication.

Patients with intractable epilepsy who were taking Depakote were compared with those who were taking other epilepsy medications and with healthy controls. MRI scans showed that those taking Depakote had thinning of the parietal lobes of the brain, had lower total brain volume, and lower white matter volume. This was a small study, but it was conducted because of previous reports of brain atrophy. Fortunately, those previous reports showed that brain atrophy was reversible when the medication was stopped. If you are taking sodium valproate for migraine headaches or a mood disorder, do not stop taking it without consulting your doctor since stopping it suddenly can worsen your condition and in epilepsy patients, cause seizures. But do discuss alternative options with your doctor, although some people may not be able to stop it if no other drugs provides relief of their symptoms.

Acute treatment of episodic and chronic migraine headaches in the US leaves a lot to be desired. Results of the American Migraine Prevalence and Prevention Study lead by Dr. Richard Lipton indicates that the acute treatment of migraine headaches in patients with chronic migraines is significantly worse than in patients with episodic migraines. Chronic migraines are defined as those occurring on 15 or more days each month, while patients who have 14 or fewer migraines a month are classified as having episodic migraines.

The researchers developed a specific questionnaire to assess acute treatment of migraine headaches. The questionnaire evaluated the effect of treatment on people’s functioning, how rapid was the relief, relief consistency, recurrence risk, and tolerability or side effects. They examined responses from 8612 persons who met criteria for migraine (chronic migraine = 539; episodic migraine = 8073). The treatment scores were significantly lower for persons with chronic migraine vs episodic migraine. The conclusion was that the questionnaire was a robust tool for measuring treatment optimization and that acute treatment was suboptimal for both episodic and chronic migraines, particularly for chronic migraines, suggesting that there are opportunities for improving care.

Art Credit: JulieMauskop.com

Candesartan (Atacand) is a relatively new blood pressure medication in the family of ACE receptor blockers (ARBs), which is also effective in the preventive treatment of migraine headaches. Another ARB, Benicar, or olmesartan has also been shown to be effective in preventing migraine headaches. Propranolol (Inderal), a beta blocker, is one of the oldest preventive drugs for migraines and many doctors often use it first. A recent study by Norwegian doctors compared candesartan with propranolol and placebo. They conducted a triple-blind, double crossover study, with 72 adult patients with episodic or chronic migraine, recruited in an outpatient clinic and through advertisements. Participants underwent three 12-weeks’ treatment periods on either candesartan (Atacand) 16 mg, propranolol slow release (Inderal LA) 160 mg, or placebo. The primary outcome measure was days with migraine headache in a 4 week period. They also looked at days with headache, hours with headache, proportion of responders (50% reduction of migraine days from baseline), and side effects.

Their analysis showed that candesartan and propranolol were equally effective and both were superior to placebo. Both drugs had more side effects than placebo, but side effects were different. The researchers concluded that candesartan should be included in the arsenal of drugs recommended for migraine prevention. The advantage of ARBs, such as Atacand and Benicar, is that unlike beta blockers they do not slow down the heart rate, which can be a problem during exercise. During exercise heart rate increases to deliver more blood to the muscles and lungs, but propranolol prevents this increase in the heart rate, which makes people feel tired, short of breath and not able to exercise as hard as they’d like. This is a significant problem since I recommend regular aerobic exercise as the first and the most important preventive treatment for migraine (and tension-type) headaches.

Art credit: JulieMauskop.com

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.

Photo credit: JulieMauskop.com

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