Treatment of Migraine

Marcia Wilkinson, M.D.

The City of London Migraine Clinic, London, United Kingdom.

(Headache 28:659-661, 1988)

INTRODUCTION

I am extremely honored at being asked to deliver The John R. Graham Lecture on the treatment ofmigraine. This lecture is named after one of the most outstanding clinicians of our time, and Dr. Graham'sknowledge and interest in migraine are well known to all of us who study it. Many of us here have had theprivilege of working with him and learning his approach to migraine and especially to migraine patients, andwe are all familiar with his numerous contributions. However, many of us will probably remember him best asbeing a superlative clinician, an excellent host and a very good friend.

As Dr. Spierings has pointed out, migraine is a very common condition. Therefore, treatment of migraineand headache is an immense problem, both medically and socially, and it can be divided into four mainaspects of which the first one is the prevention of attacks by the avoidance of trigger factors. However, beforethe trigger factors can be avoided, they have to be identified, and this is a very important part of thephysician's duty. Unless the physician himself is prepared to have a fairly detailed interview with the patient,the full account of the patient's symptoms will not be obtained. The second aspect is the use ofnon-medication treatments such as relaxation therapy, biofeedback, acupuncture, or various forms of folkmedicine. The third aspect is the treatment of the acute attack and I have been particularly fortunate in seeingand treating many patients actually in their attacks. Only if these three ways of treatment have not beeneffective should long-term prophylactic therapy be necessary. Quite frequently two or more of these ways oftreating migraine are combined.

AVOIDANCE OF TRIGGER FACTORS

Most migraineurs know themselves what may bring on attacks and if these causes can be avoided thefrequency and intensity of the attacks is lessened. Migraine sufferers may be unable to, for example, drive acar, type, read or sew. Driving a car may also be particularly hazardous while experiencing a visual aura.

A significant precipitating factor is stress, whether emotional or physical, or relaxation after it. From myown experience I find that most patients with migraine do not think that their actual attacks come on whenthey are stressed. For instance, it is rare for students to have a migraine just before an exam but rather theattack occurs a few days earlier or after it. Also, too strenuous exercise may bring about a migraine attack.Appenzeller1 has done an interesting study on people who got headaches when they were taking part in theOlympic games.

In women hormonal changes can be a strong precipitating factor of migraine attacks although I find thattrue menstrual migraine is rather rare. In the last year one of my colleagues has been trying to find patientswith true menstrual migraine, i.e. those women who have headaches associated with definite days of themenstrual cycle, and he found only 3 out of 600 to 700 patients. Certain groups of food, like citrus fruits,chocolate or dairy products, particularly cheese, can cause attacks in certain individuals. A number of othertrigger factors are often mentioned and these include adverse weather and working conditions, unpleasantodors or sounds. Not all of these factors operate in every patient and careful history taking will help to identifythe relevant ones for each of them. The physician should encourage all his patients to keep diaries of theirheadaches as these are often very helpful in identifying the particular problems. On the basis of these diariesthe physician can give advice on how to avoid some of the trigger factors, and, hopefully, to prevent attacks inthis way.

However, trigger factors can not always be avoided and more often than not the patient eventuallydevelops a migraine attack. One of the ways to treat it is non-medication treatment. Of the non-medicationtreatment methods, relaxation exercises, acupuncture and biofeedback are worth trying because this kind oftreatment diminishes the amount of medication the migraine patient needs to take. To illustrate how far somemigraine patients can go in the amount of our patients who took 315 tablets of antimigraine

of our patients who took 315 tablets of anti-migraine and other medications per week, accompanied by eye-dropsfrom time to time. This means that she took one tablet per half hour, night and day (Table 1).

Table 1Medications Taken in One Week by a Migraine SuffererEquagesic 56 tabletsAmylobarbitone 42 tabletsStemetil 42 tabletsDixarit 42 tabletsLimbritol 21 tabletsNicotinic Acid 42 tabletsTuinal 14 tablets"Arthritis" medicine 56 tabletsTotal 315 tablets

SYMPTOMATIC TREATMENT

For the past 17 years I have worked at The City of London Migraine Clinic where we developed a system bywhich patients who have an attack can come to the clinic without an appointment and can be seen and treated fortheir headache. The City of London is a great center of commerce and at least three quarters of a million peoplework there so it is conveniently situated for anyone who has a headache.

Our treatment is extremely simple. The four main elements in it are sleep, an antinauseant, simple analgesicsand, in about one third of patients, ergotamine tartrate, either as a suppository or by inhalation. Most patients withmigraine get relief from this treatment in 3 to 4 hours. Caffeine should, if possible, be avoided as it is a stimulantand prevents the individual from going to sleep. The antinauseants of choice are metoclopramide anddomperidone. As these are dopamine-2-antagonists, they promote normal gastrointestinal activity rather thandepressing it as the phenothiazines tend to do.

My colleague, Dr. Volans,2 has demonstrated that in migraine patients, while headache-free, the absorption ofsalicylate is identical with that of non-migraine sufferers. On the other hand, during the acute attack the measuredsalicylate levels in the migraine patients is significantly depressed, as compared with healthy controls and themigraine patients in the attack-free period. However, this disturbance of absorption can be corrected by theadministration of 10 mg metoclopramide intramuscularly, 10 minutes before giving the aspirin or any otheranalgesic.

Dr. Graham has contributed enormously towards the use of ergotamine in migraine. Until 15 years ago it wasnot possible to measure plasma levels of this medication when given in therapeutic doses. Until Rosenthaler andMunzer3 devised a new technique, one could only measure doses of 5 mg or more and, as we know now, these aretoxic doses. Also the absorption of ergotamine is very variable and this has been demonstrated in a study in whichergotamine was administered by mouth, suppository or inhalation to 8 female and 8 male volunteers.4 None of oursubjects had any appreciable amount of medication in the blood when it was given by mouth, but whenadministered rectally or by inhalation, half of the patients had measurable blood levels. Some patients findergotamine effective when inhaled but there are others who get nauseated if ergotamine is given by this methodand instead prefer to use half a Cafergot suppository, i.e. 1 mg ergotamine tartrate. Caffeine, being a stimulant,should not be used in the treatment of the migraine attack because sleep is part of the natural recovery process.The dose of ergotamine should be 1 to 2 mg per attack and probably not more than 4 mg per week, that is to say, itshould not be taken more than two times per week. If the patient takes more than that he is apt to developergotamine-rebound headaches. This is a difficult condition to treat unless the physician accepts the fact that thetreatment itself can give rise to headaches.

A group of 310 patients receiving the above treatment was analysed in order to assess its efficacy.5 Themajority of patients were better after 180 minutes: forty percent of the patients were symptom. free, 51% had slightresidual headache, and 9% were slightly improved. The real achievement was that none of the patients got worse.The significant factors affecting the rate and extent of recovery from the acute attack were the duration ofheadache before the patient came to the clinic, the kind of medications taken prior to the initiation of treatment, andwhether the patient slept. Patients who were able to sleep did better than those who only rested or dozed.

PROPHYLACTIC TREATMENT

If a patient has more than two attacks of migraine per month and wants to be on regular treatment, prophylacticmedication therapy should be used. In patients who are depressed and have migraine amitriptyline can be veryeffective. The four beta-adrenoceptor blockers that, so far, have been most often recorded as being useful inmigraine are propranolol, metoprolol, timolol, and atenolol. Antiserotoninergic and antihistaminergic medicationssuch as cyproheptadine and pizotifen can be quite effective in the prophylactic treatment of migraine but thepatients using them may gain a considerable amount of weight.

Dr. Graham has great experience with the use of methysergide, and this can be a very effective medication butis not easy to use because of its many side effects. These include retroperitoneal, pleuropulmonary and endocardialfibrosis as well as nausea, vomiting, muscle weakness and myalgia.

Clonidine was one of the first medications to be used prophylactically in migraine but it is probably not soeffective as some of the newer prophylactic agents such as propranolol. Its great advantage is

that it has relatively few side effects, the main ones being depression and drowsiness. Recently, thenon-steroidal anti-inflammatory medications have been used prophylactically and some, including naproxen,have given promising results.

The newest group of medications on the market for the prophylaxis of migraine are the calcium channelblockers and of these flunarizine and nimodipine have undergone extensive trials. The first results areencouraging but more trials need to be done. It is important that in the future all patients included inmedication trials should be classified according to the new International Headache Society'srecommendations. It is only if this is done that there can be true comparison between trials. It is alsoimportant that the trials be well-planned, last for a minimum of 4 months and preferably include at least 50patients.

REFERENCES

1. Appenzeller O, Atkinson R: Neurology of sports and exercise, in Bove AA, Lowenthal DT (eds):Exercise Medicine. Physiological Principals and Clinical Applications. New York, Academic Press,1983, pp 185-227.

2. Volans GN: The effect of metoclopramide on the absorption of effervescent aspirin in migraine. Br JClin Pharmacol 2:57-63, 1975.

3. Rosenthaler J, Munzer H: 9,10-Dihydroergotamine: production of antibodies and radioimmunoassay.Experientia 32:234-235, 1976.

4. Graham AN, Johnson ES, Persaud NP, Turner P, Wilkinson M: Ergotamine toxicity and serumconcentrations of ergotamine in migraine patients. Hum Toxicol 3:193-199, 1984.

5. Wilkinson M, Williams K, Leyton M: Observations on the treatment of the acute attack of migraine. ResClin Stud Headache 6:141-146, 1978.