Migraine: Diagnosis, Prevention And Treatment

Jay A.Van Gerpen, M.D., Stephen Hickey, M.D., and David J. Capobianco, M.D.
Jay Van Gerpen, M.D. is with the Department of Neurology, Mayo Clinic Rochester, MN.
Stephen Hickey, M.D. is a Neurologist in private practice in Jacksonville Beach.
David Capobianco, M.D. is with the Department of Neurology, Mayo Clinic Jacksonville.

Background

Migraine is a common, but underdiagnosed and undertreated malady.1,2 Estimates of the American Migraine Study suggest that 23 million persons older than 12 years of age have migraine headaches, with a 17.6% prevalence in females and 5.7% in males.1 The majority of migraineurs who seek medical attention consult primary- care physicians.2 Therefore, it is important for the generalist to be conversant with the diagnosis, prevention and treatment of migraine.

It is useful to conceptualize the patient with migraine as having an inherited susceptibility to headache.3 A so-called "migrainous threshold" likely exists in migraineurs, which consists of balanced excitatory and inhibitory neural circuits.3 This balance may be perturbed by a wide variety of exogenous and endogenous factors, which can lower the migrainous threshold, resulting in migraine. The variability of these migraine "triggers" in different patients, and even in individuals, supports the concept of a multi-faceted substrate for the occurrence of migraine.4 The primacy of trigger-identification in the prevention of migraine will be discussed.

An in-depth analysis of current thoughts on the pathophysiology of migraine is beyond the scope of this article; however, suffice it to say that the previous concept of migraine being a primary vascular phenomenon is untenable.3,5 The importance of serotonergic circuitry in the brainstem in the pathogenesis of migraine is now clear.5 Its perturbation can lead to not only intracranial and extracranial vasoconstriction and dilation, but also activation of pain receptors of the so-called trigeminovascular system.3,5 This knowledge will prove useful in comprehending the rationale behind migraine pharmacotherapy, particularly acute treatments, discussed below.

Diagnosis Of Migraine

The recognition of migraine has been enhanced by the introduction of diagnostic criteria for both migraine with and without aura (formerly known as "classic" and "common" migraine, respectively) by the International Headache Society (IHS).6 These are listed in Tables 1 and 2. Table 3 contains features distinguishing migraine from the other two most common headache disorders, tension and cluster.4 Particularly salient diagnostic features from these tables, as well as additional clinical pearls, include: migraine headaches are not necessarily unilateral; the patient's activity during the headache is particularly helpful diagnostically (migraineurs lie still, patients with cluster headache pace or rock back and forth, and the activity of those with tension headaches is largely unaffected); individuals may experience more than one variety of migraine, or even different headache disorders (typically migraine and tension); many patients with a history of motion sickness (especially carsickness during childhood) are migraineurs;7,8 headaches associated with nausea +/- vomiting after minor head trauma are probably migrainous (so-called "footballers migraine");9,10 and migraine frequently manifests initially in childhood with cyclic vomiting and abdominal pain, carsickness, "footballers migraine" or combinations thereof.8,11,12

Table 1. International Headache Society
Criteria For Migraine Without Aura6

  1. At least 5 attacks that fulfill criteria in B, C, D, and E
  2. Headache attacks that last 4 to 72 hrs (untreated or unsuccessfully treated)
  3. Headache has at least 2 of the following characteristics:
  1. Unilateral site
  2. Pulsating quality
  3. Moderate to severe intensity
  4. Aggravation by walking stairs or similar routine physical activity
  1. During headache, at least 1 of the following symptoms:
  1. Nausea or vomiting (or both)
  2. Photophobia and phonophobia
  3. No evidence of related organic disease

 

Table 2. International Headache Society
Criteria For Migraine With Aura6

  1. At least 2 attacks that fulfill criteria in B and C
  2. At least 3 of the following 4 characteristics:
  1. One or more completely reversible aura symptoms that indicate focal cerebral cortical or brain-stem dysfunction (or both)
  2. At least one aura symptom develops gradually over >4 min or two or more symptoms occcur in succession
  3. No aura symptom lasts >60 min
  4. Headache follows aura in <1 hr
  1. No evidence of related organic disease

 

A meticulous history is essential in assessing any headache patient. The following headache information should be elicited:

  • age of onset;
  • family history;
  • site or sites of pain;
  • duration;
  • character;
  • intensity;
  • mode of onset;
  • time between onset to peak pain;
  • temporal profile;
  • aggravating or precipitaing factors;
  • alleviating factors;
  •  
  • associated neurologic, ophthalmologic and autonomic features;
  • prior and current medication use, including dosage, schedule, and efficacy (inquiry into use of over-the-counter (OTC) medications, as well as prescribed ones, is vital);
  • caffeine use;
  • history of head trauma;
  • results of prior neuroimaging studies;
  • a complete review of systems; and
  • why the patient is currently seeking medical attention.4

Although most headaches are benign, one should be vigilant in searching for "red flags," potentially indicating more ominous etiologies, including:

  • abrupt onset of a new, severe headache ("worst headache of my life");
  • a progressive headache course;
  • onset with exertion, including sexual intercourse;
  • onset of headache during or after middle age;
  • headache associated with a decreased level of consciousness;
  • headache associated with meningeal signs, fever, indurated temporal arteries or other significant physical findings;
  • clear postural features of the headache, especially exacerbation supine and relief standing;
  • significant worsening of headache with Valsalva maneuver;
  • failure to fit a "benign" headache profile (see Table 3);
  • and any headache in a patient with a known, serious, medical condition, such as cancer, immunocompromise, or infection.13

A patient without any "red flags," whose presentation conforms to one of the common headache disorders, and with a normal physical examination, does not necessarily need any ancillary tests. For an in-depth discussion of further evaluation and treatment of headaches associated with "red flags," which may represent dangerous conditions such as subarachnoid hemorrhage; infectious or carcinomatous meningitis or encephalitis; raised intracranial pressure secondary to neoplasm, abscess, or intracranial hemorrhage; temporal arteritis or other vasculitides, the reader is directed to several excellent reviews.13-15

General Principles Of Migraine Treatment

Bartleson reminds us that the physician's approach to the migraineur is crucial in maximizing the likelihood of successful treatment.16 The doctor should strive to enter into a therapeutic alliance with the patient. This can be fostered by empathic, active listening to the patient's history, as well as by educating the patient about migraine. Patients are more likely to be active participants in their treatment if they have a better understanding of their condition.4 It may be useful to explain to patients, that they were born with a "sensitive neurovascular system," which may overreact to internal changes or external stimuli and produce migraine headaches,4 but that this condition is treatable.16

Prevention Of Migraine

More than a century ago, Sir William Osler recognized the importance of migraine precipitation by triggers and advocated that its treatment "should be directed toward the removal of the conditions upon which the attacks depend..."17 Arguably, not enough emphasis is placed on educating patients to discern potential triggers in the induction of their migraines. Table 4 lists the major, reported migraine triggers, but this list is by no means exhaustive. Discussing some of the more common ones with patients, such as menstruation, sleep and eating habits, bright light, and cafffeine is useful in preparing them to keep an effective headache diary. By having patients record the time, date, and circumstances pertaining to each of their migraine headaches, they acquire knowledge of how these may be prevented. While it is true that triggers may be variable, even in individual patients, and that some are unavoidable, Blau found that 50% of patients with intractable migraine could reduce the frequency of their attacks by 50% by eliminating various triggers.19

Table 4. Common Migraine Triggers18

Foods
  • Aged cheese
  • Alcohol (particularly red wine and champagne)
  • Monosodium glutamate (contained in seasonings and processed foods)
  • Chocolate
  • Nuts, oranges, and tomatoes
  • Caffeinated beverages
  • Nitrates and nitrites (hot dogs, sausages, luncheon meats)
  • Avocado
  • Smoked or pickled fish or meats
  • Onions
  • Aspartame (dietary sweetener)
  • Yeast or protein extracts (brewer's yeast, marmite)

Others

  • Weather changes
  • High altitude (air travel, mountain climbing)
Medications
  • Vasodilators (nitroglycerin, isosorbide dinitrate)
  • Hormones (oral contraceptives, estrogens, clomiphene, danazol)
  • Anti-hypertensives (nifedipine, captopril, prazosin, reserpine, minoxidil)
  • Histamine-2 blockers (cimetidine, ranitidine)
  • Antibiotics (trimethoprim-sulfa, griseofulvin)
  • Selective Serotonin Reuptake Inhibitors

Lifestyle

  • Fasting or skipping meals
  • Sleep (too little or too much, changes in patterns, e.g., jet lag,
  • shift changes)
  • Letdown following stess (weekends, vacations, after exams)
  • Caffeine withdrawal

Pharmacotherapy Of Migraine

Medical treatment of migraine consists of two approaches, which are not mutually exclusive: acute (also known as symptomatic or abortive treatment) and prophylactic therapy.

Acute Migraine Therapy

A wide range of medications with variable routes of administration may be used to abort migraine headaches, including aspirin (ASA), non-steroidal anti-inflammatory drugs (NSAIDs), acetaminophen (APAP), selective serotonin agonists, ergot derivatives, combination drugs (e.g., an analgesic plus caffeine), and phenothiazines. Rarely, opioids or corticosteroids may be necessary. Useful, acute migraine treatment principles include:

  • taking an abortive medication as early as possible after the onset of headache increases the likelihood of terminating it;
  • rest, and especially sleep, in a dark, quiet environment is helpful in decreasing the duration of the attack;
  • regular use of abortive medications, especially the combination drugs, can lead to chronic daily headache (also known as analgesic-rebound headaches or transformed migraine, discussed below).

A "Step-Care" treatment approach is prudent.20 This entails utilizing ASA, APAP, or an NSAID for mild-moderate headaches; if this fails, an OTC combination preparation could be tried; if nausea and vomiting are prominent, and the patient can afford to go to sleep, an anti-emetic, such as promethazine (orally or rectally) or metoclopramide, may be used along with the analgesic. In more difficult situations, a prescription combination medication (such as isometheptene/ dichloralphenazone/ APAP), an ergotamine, or a triptan may be necessary. The patient's comorbidities and other medications are important in the decision-making process as well. Table 5 lists the most commonly used acute migraine medications and doses, along with their potential adverse effects and relative costs per dose.

A few words regarding the so-called "triptans" are warranted, due to their relatively recent development and emergence as some of the most effective, acute migraine medications. These drugs are all selective serotonin (5-hydroxy-tryptamine1 [5-HT1] receptor) agonists and are thought to act by inhibiting the activation of the trigeminovascular system.21 They reverse both the pain and nausea of migraine without clouding the sensorium, are not habit-forming, and may be helpful even if administered well after the onset of headache.16 Currently, there are four triptans available in the United States: sumatriptan, zolmitriptan, naratriptan, and rizatriptan. If a patient does not respond to one, they still may respond to another.16 All are available as tablets (PO); sumatriptan also comes as a subcutaneous (SC) autoinjector and nasal spray, and rizatriptan is available as an oral-dissolving tablet. SC sumatriptan may be particularly useful in patients with severe vomiting or who have failed different PO triptans, but paradoxically should not be administered until the actual onset of headache for maximal efficacy.22,23 Naratriptan has the slowest onset of action and the longest half-life; it is therefore not the optimal choice in patients with rapid-onset migraine.22 On the other hand, the likelihood of headache recurrence often correlates inversely with its speed of onset, and thus naratriptan may be the treatment of choice in migraineurs with slow-onset attacks.22 Sumatriptan, rizatriptan, and a pharmacologically active metabolite of zolmitriptan are metabolized by monoamine oxidase and thus should not be used concomitantly with monoamine oxidase inhibitors (MAOIs).22 Theoretical adverse interactions, including the "Serotonin Syndrome," also exist between sumatriptan and selective serotonin reuptake inhibitors (SSRIs), as well as lithium.22,24 Patients taking propranolol should use the smaller dose of rizatriptan (5mg.) but this caveat does not apply to other beta-blockers.22 Chest tightness is an alarming potential side effect of the triptans, and though it probably usually stems from an esophageal origin,22 these medications are contraindicated in patients with known coronary artery disease, because of the theoretical risk of coronary vasoconstriction.16,22 Other contraindications to the use of triptans include severe peripheral vascular disease, uncontrolled hypertension, significant liver disease and migraine accompanied by significant, prolonged neurologic deficit(s) (e.g., hemiplegic or basilar migraine).16 Also, triptans, dihydroergotamine (DHE) and ergot derivatives should not be used within 24 hours of each other.16

A final point regarding acute migraine treatment that cannot be over-emphasized, is the risk of migraineurs developing analgesic-rebound headache. This vicious cycle, the cause of the majority of cases of chronic daily headache (CDH), is set in motion by the overuse of abortive therapies, including OTC medications.20 Although virtually any immediate-relief medication may induce this process (even the triptans), combination drugs, particularly ones containing caffeine, ergots, barbiturates or narcotics, are notorious for doing so.25 The risk of this phenomenon occurring increases significantly if these medications are used more than three times per week.20 Patients consistently requiring this much acute migraine medication are usually best served by being placed on a prophylactic medication.

Prophylactic Migraine Therapy

Initiating prophylactic therapy depends to a great extent on patient preference, but there are some useful, general guidelines. Prophylactic migraine medications are indicated if: attacks occur more than 2-3 times a month; attacks last more than 48 hours; migraines are so severe, that the patient is unable psychologically to cope with them; abortive therapy(ies) are inadequate or cause significant side effects; attacks are associated with prolonged aura.4 Unfortunately, a majority of migraineurs only obtain a 55-65% reduction in headache frequency on preventive medications.4 Thus the goal of migraine prophylaxis is to decrease the frequency and severity of attacks. Patients should be told that prophylaxis is infrequently curative, so that they have realistic expectations.26 Potential pitfalls in implementing migraine preventive therapy should be emphasized:4 "prophylactic failures" often are secondary to inadequate dosing or trial periods (one to two months, minimally, are typically necessary before improvement occurs); once successful prophylaxis is achieved, it need not be continued indefinitely, but gradually discontinued after 9-12 months;27 prophylaxis initiated in a patient who is abusing analgesics will likely fail; with the patient off of the analgesics, that same agent may be an effective prophylactic;26 since the prophylactic medications are potentially teratogenic, women of childbearing potential should not be placed on one unless they are utilizing reliable birth control, preferably barrier contraception.26

Medications from several different drug classes may be useful prophylactic agents. While there is some variance in expert opinion about which medications are the most efficacious,4, 26 which is complicated by the paucity of well-designed trials implemented to answer this question, there is a relative consensus that first-line medications include certain beta-blockers, such as propranolol and nadolol; the tricyclic anti-depressants (TCAs) amitriptyline and nortriptyline; and the anti-convulsant divalproex sodium (VPA).4,16 As with acute migraine treatment, choosing the most appropriate agent for a given patient should entail consideration of coexisting illnesses and medications taken regularly, so that the prophylactic medication with the highest benefit/risk ratio can be selected.26 Once done, prescribing a medication heeding the old saw, "start low and go slow" is prudent.4 Table 6 contains the most commonly used prophylactic migraine medications, along with their dosing, cost , and pertinent clinical information. Several points worth highlighting include: in patients without reactive airway disease, brittle diabetes mellitus, or some other contraindication, a beta-blocker is a good first choice; why some beta-blockers are useful for migraine prophylaxis and others are not is unknown;26 if one of the beta-blockers that is useful as a migraine prophylactic is ineffective in a given patient, that same patient might benefit significantly from another;4, 26 starting one of the tricyclics is particularly appropriate in a migraineur with concomitant depression, and a reasonable initial dose is 10 mg at bedtime, titrating up by 10mg daily every 3-5 days to an initial plataeu dose of 30-50mg nightly; while prophylactic monotherapy is ideal, some patients with severe and frequent migraine headaches, who have failed various monotherapies, may improve on dual prophylactic agents, e.g., utilizing VPA plus either a beta-blocker or TCA.4

Conclusion

Migraine is the most common cause of severe, recurring headache. It is estimated that American businesses lose upwards of 50 billion dollars annually, because of absenteeism, reduced worker productivity, and medical expenses secondary to migraine.16 The unquantifiable amount of human suffering is obviously enormous. However, migraine can be effectively treated, and sometimes even prevented. Migrainous triggers may not always be apparent, even with compilation of a meticulous headache diary by the patient, nor preventable even when identified. Similarly, neither a particular abortive nor prophylactic migraine therapy is universally efficacious. Thus, combined treatment and prevention approaches are most likely to succeed. Moreover, heightened patient awareness of migraine's pervasiveness and core features, coupled with greater diagnostic acumen and therapeutic knowledge of migraine among all physicians, are essential to significantly diminish migraine's deleterious effects.

REFERENCES

  1. Stewart WF, Lipton RB, Celentano DD, Reed ML. Prevalence of migraine headache in the United States: relation to age, income, race, and other sociodemographic factors. JAMA. 1992; 267:64-69.
  2. Lipton RB, Stewart WF. Migraine in the United States: a review of epidemiology and health care use. Neurology. 1993; 43 (Suppl 3):S6-S10.
  3. Lance JW. Current concepts of migraine pathogenesis. Neurology. 1993; 43 (Suppl 3):S11-S15.
  4. Capobianco DJ, Cheshire WP, Campbell JK. An overview of the diagnosis and pharmacologic treatment of migraine. Mayo Clin Proc. 1996; 71:1055-1066.
  5. Silberstein SD. Advances in understanding the pathophysiology of headache. Neurology. 1992; 42 (Suppl 2):6-10.
  6. Headache Classification Committee of the International Headache Society. Classification and diagnostic criteria for headache disorders, cranial neuralgias and facial pain. Cephalalgia. 1988; 8 (Suppl 7):1-96.
  7. Grunfeld E, Gresty MA. Relationship between motion sickness, migraine and menstruation in crew members of a "round the world" yacht race. Brain Res Bull. 1998; 47(5):433-436.
  8. Aromaa M, Sillanpaa ML, Rantava P. Childhood headache at school entry: a controlled clinical study. Neurology. 1998; 50(6):1729-1736.
  9. Matthews WB. Footballers migraine. BMJ. 1972; 2:326-327.
  10. Solomon S. Posttraumatic migraine. Headache. 1998; 38:772-778.
  11. Lanzi G, Balottin U, Ottolini A, Rosano Burgio F, et al. Cyclic vomiting and recurrent abdominal pains as migraine or epileptic equivalents. Cephalalgia. 1983; 3(2):115-118.
  12. Fenichel GM. Clinical Pediatric Neurology. 3rd ed. Philadelphia: W.B. Saunders Company, 1997:79-82.
  13. Edmeads J. Headache. 4th ed. Dorval (Quebec): Sandoz Canada, 1992.
  14. Newman LC, Lipton RB. Emergency department evaluation of headache. Neurol Clin. 1998; 16(2):285-304.
  15. Rubino FA. Initial evauation of headache. J Fla Med Assoc. 1997; 84:20-33.
  16. Bartleson JD. Treatment of migraine headaches. Mayo Clin Proc. 1999; 74:702-708.
  17. Osler W. The principles and practice of medicine. New York: Appleton and Co, 1982: 958.
  18. Lewis TA, Solomon GD. Advances in migraine management. Cleve Clin J Med. 1995; 148-155.
  19. Blau JN. Migraine: theories of pathogenesis. Lancet. 1992; 339:1202-1207.
  20. Sheftell FD. Role and impact of over-the _counter medications in the management of headache. Neurol Clin. 1997; 15(1):187-197.
  21. Pauwels PJ, John GW. Present and future of 5-HT receptor agonists as antimigraine drugs. Clin Neuropharmacol. 1999; 22(3):123-136.
  22. Peatfield RC. Migraine: which triptan? Hosp Med. 1999; 60: 277-280.
  23. Bates D, Ashford E, Dawson R, et al. Subcutaneous sumatriptan during the migraine aura. Neurology. 1994; 44: 1587-1592.
  24. Mathew NT, Tietjen GE, Lucker C. Serotonin syndrome complicating migraine pharmacotherapy. Cephalalgia. 1996; 16:323-327.
  25. Mathew NT. Transformed migraine, analgesic rebound, and other chronic daily headaches. Neurol Clin. 1997; 15(1): 167-186.
  26. Tfelt-Hansen P. Prophylactic pharmactherapy of migraine: some practical guidelines. Neurol Clin. 1997; 15(1): 153-165.
  27. Diener H-C, Limmroth V. The treatment of migraine. Rev Contemp Pharmacother. 1994; 5:271-284.
Jacksonville Medicine / April, 2000

 

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