Petadolex
Good News for Migraine Sufferers
By
Lane Lenard, PhD
Although almost everyone gets headaches, sometimes really painful ones, those who have suffered through migraine attacks are keenly aware that these are an altogether different species. As early as the 4th century BC, Hippocrates described how his own migraine attacks began with an aura, a bright shining light (usually in his right eye). Shortly thereafter, a violent pain struck his temples and eventually spread to his entire head and neck.
Auras, like those Hippocrates experienced, are certainly the most distinctive feature of the migraine syndrome, but these hallucination-like neurologic storms are actually quite uncommon. Only about 10% to 20% of migraneurs get them. Much more common are the pain, of course, as well as nausea, vomiting, and a hypersensitivity to lights, sounds, or smells. Rarely, people in the midst of a migraine attack experience a kind of altered state of consciousness. There’s nowhere to hide from a migraine, but for many people, a dark, quiet room seems to make the experience a little less intolerable.
A migraine is rarely a once-in-a-lifetime event. Some people get migraines (about 16% of all headaches), but many more never have the pleasure. Women tend to be more susceptible than men. According to the National Headache Foundation, migraines affect one in four households. For more than 11 million people, migraine symptoms can be moderately or severely debilitating. The frequency of migraine attacks varies wildly from person to person. Some people get them only once or twice a year, while others may suffer through two or more a week. (1) Migraines also tend to run in families.
My migraines, which are of the mundane non-aura variety, began in my early 20s. (I’ve occasionally mused that if I had to go through such an excruciating experience, it’s a shame I couldn’t at least have the light show to go with it.) Once or twice a year I would be struck by a rapidly progressing pain that felt like my head was locked in a vise that kept getting tighter with each tick of the clock. As the pain mounted, I would become nauseated and eventually vomit. The vomiting seemed to provide a relief, because, thankfully, soon afterward I would usually be able to fall asleep. When I woke up an hour or two later, more often than not, the pain would be significantly less. Although the pain might hang around at a lower level for a day or so, it never reached its previous crescendo.
Once the migraine cascade began, there was no way to stop it. The most potent painkillers were useless, even if I could keep them down. Many migraneurs have it a lot worse than I do. Once the vise started to tighten on my skull, I could close the door, shut off the lights and ride it out in a few hours. For some people, attacks like these can go on for 3 or 4 days.
Anti-Migraine Strategies
There are generally two means of treating migraines: 1) halting, or aborting an ongoing attack, and 2) preventing attacks from starting in the first place. Although the precise physiologic mechanisms that cause migraines are not completely understood, inappropriate dilation (and constriction) of arteries in the brain and scalp seem to be involved. The drugs that successfully abort attacks, including the ergots and the triptans, both affect the mechanisms that control vasodilation. Some of the measures aimed at preventing them also target vascular muscle tone, while others take different approaches.
Stopping an Attack in its Tracks
If you’re in the midst of a major migraine attack, especially a really bad one, and you can take something that stops it in its tracks and restores you to a semblance of a normal nonmigraine state within an hour or two, it certainly feels like a miracle. Recently, drugs capable of doing just this have become available, and speaking as a card-carrying migraneur, I can unequivocally state that using the word miracle to describe what these drugs do is not overstating the case by much.
Various drugs have been used over the years to treat ongoing migraine attacks. Since the 1920s, a group of drugs known as the ergot alkaloids* (eg, ergotamine, dihydroergotamine, or DHE) have been the most successful. However, these have been difficult to administer (typically requiring an intramuscular injection†) and can have serious adverse effects. For these reasons, they were generally relegated to emergency room use.
The major breakthrough in migraine treatment came with the introduction of sumatriptan (Imitrex®) and related drugs (known as triptans) over the last decade. I first tried Imitrex in the mid-1990s. At that time, the frequency of my migraines seemed to be increasing, sometimes to two to three or more per month. Although most were not nearly as severe as those described above, they were often bad enough and could go on for 2 to 4 days at a time. Soon after Imitrex became available, I obtained a prescription, and the next time the screws started to tighten on my skull, I injected it (subcutaneously, using a special patient-friendly device). Within minutes, the pain began to dissolve, and in less than half an hour, it was virtually gone. It really was a miracle!
The only side effect of Imitrex—for me—was some minor flushing and slight muscular discomfort, which lasted only a few minutes. The major imwww.e problem with the drug (in addition to its outrageous cost, about $50 a shot!) was an annoying tendency for the headache pain to return within 24 hours. Known as the rebound, this has become a notorious—and generally unsolved—issue with Imitrex and the other triptans. When a rebound occurs, another dose is often required.
The availability of Imitrex pills a year or two later made it even easier to abort a migraine attack. I found that these worked well, but only if I could catch the headache at its very earliest stages. If I wait too long—and sometimes that line is hard to judge—they are useless, and I wind up taking a shot as well. Also, Imitrex pills do not overcome the rebound problem. Thus, I may end up taking them for 2 or 3 days in a row (at about $10/pill) until the rebounds subside. Despite these drawbacks, these drugs have demoted migraine for me from a major—and regular—medical problem to, at worst, a nuisance.
As effective as they are, though, the triptans are not for everyone and can be very dangerous for some. In particular, people with a history of any kind of underlying cardiovascular disease should not use them without close physician supervision, because they can lead to potentially dangerous cardiac ischemia, similar to that which occurs during an attack of angina pectoris.
Preventing Migraine Attacks
Once it became clear that I could successfully manage my ongoing attacks, I started to focus on preventing them in the first place. While it was great to be able to manage ongoing migraine attacks, I was still getting them nearly every week, and they often lasted at least two days. If you do the math, that adds up to a lot of migraine days.
Obviously, Imitrex had no ability to reduce the frequency of attacks, and it may actually increase them, because it seemed as though the more I used Imitrex, the more frequently the headaches came along. A prescription of Imitrex pills consists of a card containing nine pills each in its own individual protective bubble pack. While nine pills were usually enough for a month (especially with a shot or two thrown in), often it wasn’t. Was I hooked? There is one report in the scientific literature suggesting that what amounts to a drug dependence can occur with Imitrex. (2)
Traditional prophylactic treatment for migraine consists of: 1) avoiding specific migraine triggers, which are thought to stimulate attacks, and 2) taking drugs (or non-drug treatments) that tend to promote vasodilation and or relaxation/stress reduction. The most commonly mentioned triggers are foods, such as aged cheeses, alcohol, MSG, chocolate, caffeine, pickled or fermented foods, yeast, onions, nuts, aspartame, and others. Other supposed triggers include menstrual cycle, stress (or relief from stress), irregular sleeping and eating patterns, and even changes in weather, altitude, and time zone (jet lag). Needless to say, avoiding these triggers—as best I could—made no difference in my migraine frequency. Experts today are starting to downplay the importance of migraine triggers. Not only are they virtually impossible to avoid for most people, the evidence that they actually do consistently stimulate attacks is sketchy at best. (3)
Most serious prophylactic efforts focus on the chronic use of one or more drugs, which have various putative (ie, theoretical) rationales. These drugs are classified as antihypertensives (blood pressure-lowering), which are thought to normalize blood flow in the brain and scalp; antiepileptics, which may work by quieting any neurologic storms raging in the brain; and antidepressants, especially selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants, which affect activity of serotonin and other neurotransmitters in the brain.** Since the ergots and triptans seem to abort migraine attacks via their effects on certain serotonin receptors in the brain, any beneficial prophylactic effects of these drugs, which include Prozac®, Elavil®, and others, could presumably be due to their neurotransmitter activities.*
The fact is, though, that no convincing data exist to prove that any of these drugs are particularly effective for preventing migraine. Published reports of clear-cut success are few and far between, and no pharmaceutical company, which would jump at the chance to legally promote its drug to prevent such a common, chronic affliction, has ever received approval from the FDA to do so. At my regular physician’s behest, I tried a number of these drugs, with—no surprise —no benefits at all. In addition, I had tried some natural remedies that were supposed to reduce migraine frequency—eg, feverfew, high-dose 5-hydroxytryptophan (5-HTP), homeopathics—but also to no avail.
Enter Petadolex
Thus, it was with a significant degree of skepticism that I embarked on the good ship Petadolex. I had virtually given up any serious attempts to prevent migraines and assumed that either the migraines would go away of their own accord some day (My mother’s did), or else I’d live the rest of my life taking Imitrex, or hopefully, its less expensive generic equivalent. While trying out a new primary care physician, who had decidedly less conventional, more natural, more nutritional leanings, I mentioned my migraines. He wrote the word PETADOLEX on a prescription pad and said there was some evidence that it helped reduce migraine frequency. I should be able to order it over the Internet, he said.
In researching Petadolex, I found some limited—but interesting—clinical data, as well as a lot of circumstantial evidence. It seemed to be worth a try, although I had few expectations of success. So I ordered a couple of bottles, with the caveat from my physician and the product label, that you need at least two months of steady use and possibly more to see any beneficial effect. What did I have to lose, as long as I had plenty of Imitrex in the drawer?
I found that Petadolex is a purified extract of the perennial herb Petasides hybridus, also known as butterbur root, which grows throughout Europe, Asia, and North America. It has been used medicinally for centuries to treat plague, fever, cough, asthma, and skin wounds. Petasites hybridus has at least two active ingredients:
Petasin reduces spasms in smooth muscle and vascular walls, with a special affinity for blood vessels in the brain; it also provides an anti-inflammatory effect by inhibiting leukotriene synthesis.
Isopetasin modulates the metabolism of prostaglandins, which play an integral role in the expression of pain and inflammation. (4,5) Both these mechanisms of action should theoretically be useful for treating migraine, which is thought to be primarily a vascular inflammatory disease. But what does it actually do for people with migraine?
That question was answered in a randomized, placebo-controlled study (6) conducted in Germany, where herbal medications are taken far more seriously than they are in the US.*** The 12-week trial began with a 4-week period during which 60 men and women with a documented history of migraine took no medication at all to prevent attacks (washout period). For the next 8 weeks, they were divided into two groups: Group 1 took two Petadolex capsules twice daily, while Group 2 took an identical-looking placebo. The patients were asked to rate each migraine in terms of frequency, pain intensity, and duration at baseline using standard visual analog scales (eg, minimal pain =1, maximal pain=10) at the end of the washout period (week 0) and again at Week 4 and Week 8 of treatment.
The results of the trial were striking. After 8 weeks of treatment, the Petadolex group was experiencing significantly fewer migraines than the placebo group (Fig. 1). At baseline, the Petadolex group and the placebo group reported a mean of 3.3 and 2.9 attacks, respectively, for the preceding 4-week period. By week 8, the Petadolex group reported only 1.3 attacks, compared with 2.4 for the placebo group. This represents a 60% improvement of the Petadolex group.
Pain intensity followed a somewhat different pattern, but still showed significant improvement for the Petadolex-treated group (Fig. 2). Here the Petadolex group reported significantly less severe headache pain at Week 4, but there was no significant difference at Week 8. Migraine duration showed a similar reduction that was significantly shorter only at Week 4. Overall, 70% of the Petadolex-treated group rated their treatment as beneficial, compared with just 26% in the control group. This difference was also highly significant. No adverse effects were reported related to Petadolex usage.
Reducing Imitrex Use
These results were very encouraging, but what did they mean for me? Would I be in the successful 60%? For the first two months on Petadolex, I noticed no changes. By the end of the third month, though, I had the sense that I was having fewer migraines; no way to prove it, though. Then, it occurred to me that there was a somewhat objective measure I could use to measure migraine frequency—my Imitrex use. Recall that prior to starting Petadolex, a prescription of nine pills was barely enough to get me through a month. Often I had to dig into a stash of spare pills that I had managed to accumulate or borrow some from my daughter, who had inherited my tendency for migraines. But by the end of the fourth month of Petadolex use, when I opened my medicine draw, a package of six or seven Imitrex tabs was staring back at me. I realized that I had used only two or three pills during the entire prior month. I hadn’t had a month that good in 5 or 6 years. My perception had been correct; my migraine frequency had definitely declined.
Will Petadolex ever catch on in this country and achieve the status it seems to deserve as the premiere migraine prophylactic? Given the influence of the pharmaceutical industry and the general antipathy of the US medical establishment to natural treatments, no matter how effective and safe they are, it’s hard to say. A clinical trial is currently under way in the US, with results expected shortly. In the May 2000 issue of the journal Headache, which is published by the American Headache Society (AHS), an abstract reported the promising preliminary results of the German trial described above. (7) The AHS president, Richard B. Lipton, MD, of the Albert Einstein College of Medicine, seems encouraged, calling Petadolex a promising new preventative strategy for migraine sufferers.
My personal experiment continues successfully. After about six months on Petadolex, my migraines continue to be less frequent (1-2 usually mild headaches per month), which is in accord with the results of the German study. Following the Petadolex label, I have reduced my usage from two caps twice daily to one twice daily. If the frequency remains low, I may reduce it further still. Of course, there have been no adverse side effects. Where once I worried about running out of Imitrex each month, now I always have a surplus. Maybe some day I won’t need it at all.
* Ergot alkaloids are derived from a potentially dangerous parasitic fungus that grows on the edible grain rye. In ancient times, ergot poisoning caused countless mysterious epidemics of death related to gangrene of the limbs (known as St. Anthony’s Fire). During the early 19th century, ergot was used to induce labor, but this use was soon discontinued because the risk of fetal death was very high.
† In recent years, a nasal-spray form of DHE (Migranal®), has become available. While it works quite well, it is rather awkward and complicated to self-administer.
**There is no suggestion that migraine is connected with depression. It’s just the fact that the drugs that work for depression may also have beneficial effects for migraines.
***In Germany, St. John’s wort and saw palmetto are considered primary treatments for depression and prostate enlargement, respectively, while physicians on this side of the Atlantic uniformly ridicule and ignore them, preferring more expensive, more dangerous, and sometimes less effective synthetic pharmaceutical products.
References:
1. Rasmussen BK. Epidemiology of headache. Cephalalgia. 1995;15:45-68.
2. Osborne MJ, Austin RC, Dawson KJ, Lange L. Is there a problem with long-term use of sumatriptan in migraine. BMJ. 1994;308:113.
3. Goadsby PJ, Olesen J. Diagnosis and management of migraine. BMJ. 1996;312:1279-83.
4. Eaton J. Butterbur, herbal for migraine. Nat Pharm. 1998;2:23-24.
5. Mauskop A. Petasites hybridus: ancient medicinal plant is effective prophylactic treatment for migraine. Townsend Lett. 2000;202:104-106.
6. Grossmann M, Schmidramsl H. An extract of Petasites hybridus is effective in the prophylaxis of migraine. Int J Clin Pharmacol Ther. 2000;38:430-5.
7. Mauskop A. Petasites hybridus (butterbur root) extract is effective in the prophylaxis of migraines. Results of a randomized, double-blind trial. Headache. 2000;40:420 (Abstract).