Since my migraine booklet was written the biggest single advance in the treatment of the disorder has been a family of drugs called triptans. These drugs are designed to act in certain ways like Serotonin (see migraine section elsewhere) which is implicated in the cause of migraine. Typically these drugs act at certain Serotonin receptors. Like other chemical transmitters in the brain Serotonin acts at many different sites and we now know there are lots of different receptors which have different physiological actions. The Triptans mostly act as agoists (that is having the same action as the transmitter) at Serotonin 1B/1D receptor. They seem to act most outside the brain especially on the trigeminal ganglion which is part of the trigeminal nerve. This nerve has sensory function over the face and the coverings of the brain (meninges) and transmits most of the pain sensation during a headache. The trigeminal nerve is implicated as part of the mechanism for secretion of certain chemical substances that increase pain and inflammatory responses. In Addition Triptans act on certain blood vessels causing them to constrict. Recall that a good deal of the pain in migraine is caused by blood vessels expanding or dilating. Blood vessels being pain sensitive structures, during a migraine headache you classically may feel a pounding, corresponding to the sensation of blood going through dilated irritated vessels.

Triptans don’t differ too much in their efficacy especially if you take into consideration that they have rarely been compared in the same study "head to head". Efficacy for typical migraine headaches runs in the range of perhaps 60-80 percent. There is some chance that a drug which didn’t work on one occasion may work, when tried again, on another headache. In fact lots of people suffer from more than one headache type. Sometimes they have a tension headache, at other times a migraine, at others sinus pains, and triptans seem to be specific for migraines. Conversely lots of people think they have a variety of headache types but what they really have is migraine only in its various manifestations and all of their headaches may be treatable with triptans. Cluster headaches as a group are under-treated with triptans. These terrible headaches are more likely to respond to Imitrex nasally administered or injected or to Migranal, nasally administered DHE. Instead, Cluster sufferers end up using second line therapies that are much less effective. Unfortunately clusters tend to occur in middle aged men smokers and that increases the risk for coronary artery disease which is a contra-indication for the group of triptans as a whole.

The different drugs are practically alike and different physicians have a repertoire of one or two personal favorites. It does not seem to make a great deal of difference. Those available now have relatively short durations of action which means that a headache treated with any one of these drugs often returns. This is termed rebound and requires repeating a dose of medicine, often not a terrible problem. There are newer triptan agents being studied which promise a longer duration of action but they have not been released yet. In clinical practice the concept of rebound is overstated. It's been found more recently that it's important to intervene early in a headache, nip it in the bud and then a patient will be less likely to need more medicine. A drug that's partially effective is one most likely to be overused.

Triptans differ in their mode of administration. Imitrex© (Sumatriptan) the first released drug, has an oral form, but nausea and vomiting may impair oral absorption and also only a small percentage of the stuff gets into the blood under the best of circumstances when you give it orally. Other triptans seem to be better absorbed by mouth. Imitrex© is at its best, with a rapid action, when injected, but a lot of folks have to get past their prejudices to inject a drug. There is a prepared spring loaded injection which is very efficacious and a nasal form to that bypasses the gut and seems to work, despite the fact that low concentrations of the drug get to the blood when administered nasally.

Another preparation, not a triptan, but behaving similarly, is Dihydroergotamine, so-called DHE as a nasal spray whose brand name is Migranal© that is self administered. This is in an older drug class, the ergots, a cousin of ergotamine in the old preparation Caffergot©, for those familiar with it, and used as in injection in the emergency room. DHE works also on Serotonin 1D receptors but is less specific. The main advantage is its longer half life. Since the drug stays around in the blood and is not eliminated so fast, you are less likely to have rebound. A nasal shot may be another advantage since the stuff does not need to be absorbed through the gut. You’re expected to take one shot in each nostril, wait 15 minutes then do it again. DHE and the triptans are blood vessel constrictors. Indeed this is probably the main mechanism of action. That means if you have a condition characterized by narrowed blood vessels, especially atherosclerosis, cororary artery disease, angina, peripheral vascular disease and the like you absolutely cannot use these agents. Indeed we use these drugs only with some trepidation in any man of a certain age, especially a smoker or one with a positive family history of heart disease and the like and may require a stress test before an older male is allowed to take these medicines. Anyone with angina or claudication, it goes without saying, should not take these drugs. Anyone with hemiplegic or basilar migraine shouldn’t take them either.

Stadol© (butorphanol) nasal spray is sometimes used as a stopgap in migraine. We don’t care for it because it is a narcotic with some abuse potential. But again, it allows one to bypass the gut which may be important where a headache involves nausea and vomiting and to get a person rapid relief where there is a severe acute headache. It may keep the sufferer out of the emergency room. The dose is one spray in one nostril which may be repeated only once in 60-90 minutes.

Frequently we will try to use an oral drug. Which one, does not seem to matter much. If vomiting is a factor we may add a Phenergan(c)  (promethazine) suppository or try to get in early with an oral dose of Reglan (metoclopramide) to pre-empt nausea and increase oral absorption of medication. This whole group of medicines, is obviously aimed at treating the acute headache and not at all at prevention of migraine headaches which is even more important.

Revised 3/2002 © 2002 Charles Yanofsky

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