Headache

0025-7125/91 $0.00

+ .20

Migraine Headaches Seymour Diamond, MD*

The affliction of migraine knows no geographical boundaries; it favors no century or age. From the earliest writings in ancient Sumaria, migraine has been recognized. In Babylon, the "head disease" affected its victim like a "flash of lightning," rendering the migraineur to "glow as a star of heaven so that he could not find peace and had to run at night like water. "41 Early medical writings from Egypt and Greece continued to record man's search for the cause and cure of headache. In the first century AD, Areteus of Cappadocia presents the first description of migraine as a separate entity. He called it heterocrania and described it as affecting "one side of the skull, exactly up to the midline with blackness before the eyes, profuse sweating, nausea, bilious vomiting, collapse, photophobia, and osmophobia." One century later, Galen coined the term hemicrania, which is the root of the word migraine, meaning "half-a-head." Citations continue throughout the works of the medieval European and Islamic physicians. Thomas Willis, the famous English anatomist, included the "first modern treatise of migraine" in his textbook on neurophysiology and clinical neurology. 77 Although most contemporary headache specialists do not believe that there is a relationship between migraine and epilepsy, throughout the nineteenth century, the two were continually linked by British and French researchers. 33, 39, 50 In his 1873 treatise On Megrim, Sick Headache, and Some Allied Disorders, Liveing50 utilized all the prevailing theories and clinical observations on migraine. He recognized that there were endless varieties of migraine, and migraine represented its own place in a field of "allied and metamorphic disorders." Based on the work of these early physicians, the headache researchers of the twentieth century would continue their quest against migraine, EPIDEMIOLOGY The epidemiology of migraine has been investigated in several studies over the past few decades. Bille has had the unique opportunity to observe the incidence of migraine in a small Swedish town, He then completed a 30-year follow-up on the same community.4 He noted that prior to the age 13, there is no difference between the sexes in the incidence of migraine, With the onset of puberty, there *Director, Diamond Headache Clinic; Director, Inpatient Headache Unit, Louis A, Weiss Memorial Hospital; and Adjunct Professor of Pharmacology and Molecular Biology, Chicago Medical School, Chicago, Illinois

Medical Clinics of North America-Vol. 75, No, 3, May 1991

545

546

SEYMOUR DIAMOND

is a female preponderance. The average age of onset of the 73 original children with migraine was 6 years. Sixty-two per cent of these migraineurs reported a remission of migraine attacks for more than 2 years during adolescence and young adulthood; however, 22% of the original 73 had recurrence of the migraine attacks after an average of 6 migraine-free years. Between the ages of 37 and 43, 53% had migraine. Of these, 22% did not report any migraine-free years since childhood. In the United States, Linet's49 group has extensively studied the incidence of headache. In their latest report, these researchers conducted a telephone-interview study of eligible residents, aged 12 through 29 years, of Washington County, Maryland. Of 6924 subjects completing the interview, 76.5% of the women and 57.1 % of the men reported that their most recent headache occurred within the previous 4 weeks. Within the month prior to the interview, 3.0% of the men and 7.4% of the women had experienced a migraine attack. The effect of these headaches on work was substantial. Eight per cent of the men and 14% of the women had missed part of or an entire day of work or school because of headaches in the 4 weeks prior to the interview. The authors concluded that previous studies only touched on the vast expanse of headache problems. PATHOGENESIS The history of migraine diagnoses and treatment is replete with discarded theories about its pathogenesis. These theories included ophthalmologic aspects, endocrine factors, periodic obstruction of the foramen magnum, metabolic disorders, gallbladder dysfunction, allergy, and psychological problems. 9 Considerable gains were achieved by the pioneering research of Wolff. 94 In his work, he noted that migraine was a self-limited, neurogenic, sterile inflammation. Four dynamic events were identified as occurring in a migraine attack: (1) initial cerebral vasoconstriction, which is correlated with the aura or warnings of migraine; (2) the extracranial and intracranial vasodilation that Wolff considered the cause of migraine pain; (3) the sterile inflammation that increases the pain and prolongs the migraine attack; and (4) a secondary muscle contraction. Wolff theorized that the vasoconstriction that occurs during the aura involves two areas: the retina, or the retinal or ophthalmic artery, or the occipital portion of the cerebral hemisphere. By examining the bulbar conjunctival vessels during the preheadache phase, Wolff attempted to determine if there was a causal relationship between the initial cerebral vasoconstriction to the cranial vasodilatation of migraine. After infusing norepinephrine intravenously at rates that caused conjunctival vessel ischemia as well as an increased amount of extracranial artery constriction, no headache occurred following the infusion. Wolff indicated that another factor is the cause of the painful vasodilatation phase of migraine. He also observed that cerebral vasoconstriction has usually terminated before the extracerebral vasodilatation has started. In further studies, Wolff chemically induced headache and observed the effects of ergotamine tartrate on the cranial vessels. He postulated that dilatation and the distention of large arteries, as well as an increase in pain-threshold-lowering substance, result in headache. In most migraine attacks, the pain radiates from the large subsurface cranial arteries and their branches. When the vessels are distended, pulled upon, or displaced, the patient experiences aching pain. Wolff also noted that immersing the body in hot water induced dilatation of these vessels but did not necessarily cause pain. He theorized that a sterile inflammation occurs in addition to the vasodilation. This inflammatory reaction was induced, neurogenically, by a neurokinin and a proteolytic (neurokinin-forming) enzyme. Wolff believed that a transudation of fluid into cranial tissue occurs during

MIGRAINE HEADACHES

547

a migraine attack. The manifestations of this transudation occurred inside and outside the cranial cavity. During and usually late in the attack, the scalp and the arteries on the affected side are tender and may become edematous. Wolff went so far in his investigations to resect a temporal artery during a migraine attack. The pathologic report revealed edema of the arterial wall. Examination of the bulbar conjunctiva during an attack revealed gradually increasing edema about the small blood vessels, with blurring of their edges. The vessels were all dilated. At least five groups of substances, and possibly more, have been implicated with the sterile inflammation. 17 These substances include catecholamines, histamine and serotonin, peptikinins, prostaglandins, and the slow-reacting substance of anaphylaxis, an acidic lipid. Their effects include contraction and relaxation of smooth muscle, constriction or dilation of arteries and veins, induction of water and sodium diuresis, fever, wheal and flare reactions, and induction of pain, such as headache. Reduction of blood flow to the cerebral cortex has been linked to the prodromes of migraine in a few studies. 32 , 78 Throughout his investigations, Wolff noted that noxious stimulation of any part of the head triggers muscle contraction of the head and neck. Therefore, noxious stimulation caused by vascular distention will also cause muscle contraction. Emotional tension will trigger sustained contraction of the muscles of the head and neck. This sustained contraction may outlast the vascular aspects of the headache and is a secondary feature of the acute migraine attack. The studies by Olesen's group dispute the theories ofWolff. 65 These researchers injected a radioactive isotope, xenon-133, into the carotid artery. They studied induced migraine after arteriography in a series of subjects. The "spreading oligemia" that they described usually begins in the occipital region and spreads anteriorly, reaching a primary sensorimotor area after the symptoms from that region had started. The oligemia persisted after the cessation of the focal symptoms. By using this regional blood flow method, these authors proposed that the painless preheadache phase of classical migraine was possibly secondary to a reaction similar to the spreading depression described by Leao 47 and not secondary to the oligemia. Olesen et al, 64 in a previous study, observed that the striking oligemia did not occur in nonclassical migraine. Between the resting phase, the onset of nonclassical migraine and the acute attack, no significant changes were demonstrated in regional or cerebral blood flow. The authors concluded that classical and nonclassical migraine differ, at least with respect to cerebral blood flow studies. Certain difficulties with the design of these two studies cast doubt on their conclusions. Although the typical age of a migraine sufferer is in the second, third, and fourth decades, the majority of their subjects were over 40 years. Many of their subjects failed to report a family history of migraine, a trait generally accepted by headache clinicians as indicative of this disorder. In the first study,64 there was a male predominance, although most headache experts agree that approximately 60% of migraineurs are women. Finally, I have treated many migraine patients who report at least one occurrence of classical migraine and then experience nonclassical migraine throughout the evolution of their headache disorder. The patient may indicate that early in their migraine history, the prodroma occurred prior to their attacks, and eventually the headache would occur without the aura preceding the attack. Other patients may complain of headaches for several years, which are never preceded by an aura. Later in life, they will notice prodroma occurring prior to some of their acute attacks, and also in the absence of an acute headache. Skyhoj Olsen et alS6 The incidence of migraine in the general population has been established as 8% to 29% in adult women, and 4% to 19% in adult men. 37 The prevalence of depression is also higher in women, at 20%, as compared to 10% in men. Another study explored the relationship between migraine and depression in a group of patients with a depressive disorder. A greater prevalence of migraine in depressed men than in the general population was demonstrated. 54 Review studies have been conducted on patients diagnosed with the mixed headache syndrome. 45 Neuroticism, stress, excessive use of narcotics and caffeinecontaining analgesics, ergot dependency, and hypertension were factors, along with

560

SEYMOUR DIAMOND

depression, in development of this condition. A previous history of migraine was reported by the patients, and several reported dependency on habituating benzodiazepine agents. Patients with mixed headaches continuously search for relief of the problem, although they may be skeptical that the physician will repeat the errors and omissions of their previous physicians. Discontinuing medications, especially analgesics and ergots, may be very difficult for these patients because they fear exacerbation of the attacks due to withdrawal. Continuity of care with one single knowledgeable physician is essential for these patients. Education is an important factor in the care of the patient with mixed headache. Continual reinforcement may be required with regard to the problems of habituating drugs. Withdrawal from these agents is essential and must be accomplished before any therapeutic regimen can be successful. Also, the patient should be advised that previously tried drugs may be restarted, but in combination with other agents. Antidepressants The tricyclic antidepressants (TCAs) have been studied extensively in headache therapy. The treatment of chronic tension headache, including a discussion of the successful use of amitriptyline, was described by Lance and Curran in 1964. 45 The use of antidepressants in the treatment of migraine has also been studied extensively.is, 34,52 In one study, is 167 patients with a chief complaint of headache were treated with tricyclic antidepressants. Of these patients, 91 were diagnosed with migraine, 52 with depression, and 24 with migraine and depressive overlay. Eighty per cent of these patients reported excellent results following therapy. The role of the antidepressant compounds in the prophylaxis and relief of pain increasingly has been identified. Some investigators have suggested that if the antidepressant drugs had been studied for pain relief before they were experimentally administered to depressed patients, these drugs would have been classified as analgesics. The role of antidepressant drugs in pain control has been attributed to their effects on the synthesis and metabolism of serotonin (5-HT) and norepinephrine. Two studies have identified neurons containing serotonin and norepinephrine as part of the brain's analgesia system. l4 , 69 Most of the currently available antidepressants would be expected to play a role in the modulation of pain. Many studies have identified the analgesic properties of the antidepressants.7. 8,62 A decrease in the severity, frequency, and duration of migraine headaches was demonstrated during TCA therapy in each of these investigations. The TCAs have also been compared with beta-blockers in migraine prophylaxis. 46, 97 In Langohr's group:6 the beta-blockers were favored. Ziegler et al 97 suggested that both therapies were effective. The use of pizotifen and cyproheptadine, which are structurally similar to the TCAs, in migraine headache therapy was evaluated. 89 The severity and frequency of attacks were decreased in many patients. A double-blind crossover trial that compared the use of doxepin to amitriptyline in a group of patients with mixed headache was conducted. 58 The authors noted significant reductions in all headache indices as well as in the consumption of analgesics and ergotamine preparations. Citations in the literature on the response of migraine patients to the TCAs have often been sporadic, anecdotal, or contradictory. A few studies have demonstrated the TCAs as effective in migraine prophylaxis. 34, 52, 69 Of the 2000 new patients seen annually at the Diamond Headache Clinic, 425 will be diagnosed with either mixed headache syndrome or migraine and are responsive to antidepressant therapy. Selection of which TCA to prescribe is dependent on the presence of a sleep disturbance (Table 3). For those patients who complain of frequent or early awakening, the TCAs of choice are amitriptyline and doxepin. For those patients who do not present with a sleep disturbance, the TCAs of choice are protriptyline,

561

YlIGRAINE HEADACHES

Table 3. Tricyclic Antidepressants and Their Effects DRUG

SEROTONIN INHIBITION

Amitriptyline Desipramine Doxepin Imipramine Nortriptyline Protriptyline

Moderate Weak Moderate Fairly potent Weak Weak

NOREPU":EPHRINE

DOPAMIl\E

SEDATIVE

IKHIBITIOl\

INHIBITION

EFFECTS

ANTICHOLIl\ERGIC EFFECTS

Strong Mild Strong Moderate Mild None

Strong Moderate Strong Strong Moderate Strong

Weak Potent Moderate Moderate Fairly potent Fairly potent

Inactive Inactive Inactive Inactive Inactive Inactive

nortriptyline, and desipramine. A nontricyclic antidepressant, trazodone, has been used successfully in treating these patients. 27 Fluoxetine, a bicyclic antidepressant, recently has been utilized for treatment of the mixed headache syndrome. 19 Therapy with YlAOIs is indicated for patients with mixed headache that is refractory to other forms of conventional migraine therapy. In the event of TCA failure, combination therapy with an MAOI and a TCA may be considered. The use of MAOI therapy in the elderly has been evaluated. 3. 74 These agents were determined to be safer than TCAs because of the adverse cardiovascular and anticholinergic effects associated with TCAs. A review study was conducted at the Diamond Headache Clinic on the use of MAOIs alone or in combination with TCAs in the treatment of the recidivist headache patient. '" Nineteen patients with pure migraine received MAOI therapy alone. A 50% or more improvement was reported by 11 patients, and 12 of 16 patients with mixed headache noted a greater than 50% improvement, as compared to the patient with pure migraine. Treatment with the MAO Is is useful in the management of migraine, depression, and the mixed headache syndrome. The MAOIs do have potentially severe side effects that limit their use to only those patients who do not respond to other forms of prophylactic therapy, and these agents should never be considered firstline therapy. Combination therapy involving the use of the YlAOIs and TCAs have recently been gaining acceptance. 93 Schuckit et al81 demonstrated that combination therapy was a safe and effective treatment. Their report reviewed cases of morbidity or mortality associated with the use of combination therapy. Several MAOIs were cited, but only one TCA, imipramine, was identified. Amitriptyline has been demonstrated as preventing the reaction between the MAOIs and tyraminecontaining foods. 66 In the recidivist headache patient, combination therapy has demonstrated 50% or more improvement in 75% of patients with mixed headache in the study by Freitag's group.35 No significant reactions were reported, thus confirming the findings of previous reports concerning the safety of combination therapy. The physician must use careful patient selection when ordering singular YlAOI treatment or combination therapy with a TCA. The patient should have adequate trials on conventional therapies before MAOI or combination therapy is considered. Again, the dietary and medication restrictions must be carefully reviewed with the patient starting YlAOI therapy. Patients with a history of or potential for noncompliance should not be selected for MAOI therapy. The initiation of combination therapy with an MAOI and a TCA should only be undertaken in an inpatient setting. Polytherapy Combination therapy is a controversial issue that has not been confronted in most major textbooks and handbooks on headaches. Polypharmacy has been

562

SEYMOUH DIA'.IOND

identified as a pejorative term indicating unjustified and chaotic administration of several, often similar, drugs in an attempt to demonstrate intensive treatment. 72 It has also been defined as a purposeful procedure used to intensifY the effect of a single drug and affect the different elements of the complex pathophysiology of any given disease. Polypharmacy has been used extensively in the abortive treatment of migraine, although studies in the prophylactic treatment of migraine headache have been limited. 53. 72 The pathophysiology of migraine, chronic tension headache, and especially mixed headache syndrome is very complex and not completely understood, characteristics that justify polypharmacy (co-pharmacy). Beta-blockers or calcium-channel blockers may be added to the treatment regimen for these patients. The NSAIDs, including ibuprofen, fenoprofen, naproxyn sodium, diflunisal, and ketoprofen, may be beneficial in the prophylactic treatment of the mixed headache syndrome. Withdrawal Therapy A recent study evaluated 139 patients with migraine, tension headache, or both. 30 For at least 6 months, these patients developed chronic headaches that occurred at least 20 days/month. Analgesics or antimigraine drugs were consumed for more than 20 days/month. The mean number of tablets or suppositories consumed weekly prior to withdrawal was 34.6. These agents included ergots, barbiturates, and caffeine-containing analgesics. The patients were hospitalized for 10 to 14 days, during which time all drugs were abruptly discontinued. At the time of discharge from the hospital, no headache was reported by 45%; 50% or greater improvement was reported by 33% when compared with the pretreatment period. At the 3-month follow-up, improvement of 50% or more was reported by 48.5% of the patients, as compared with the pretreatment period, although less than 8% were headache-free. Also, at the 3-month follow-up, 39% of the patients were not using any drugs, and the overall drug intake had decreased dramatically. The authors concluded that the regular intake of analgesics or antimigraine drugs can precipitate a chronic daily headache and a deterioration of the underlying headache, whether the diagnosis is migraine, tension headache, or both. INPATIENT TREATMENT OF HEADACHE Admission to a specialized inpatient unit for headache treatment affords to the recidivist patient an environment specifically developed for their care. '2 HospitaliTable 4. Inpatient Headache Unit: Admission Criteria 1. Prolonged, unrelenting headache, with associated symptoms such as nausea and vomiting, which, if allowed to continue, would pose a further threat to the patient's welfare 2. Status migraine 3. Dependence on analgesics, caffeine, narcotics, barbiturates, or tranquilizers 4. Habituation to ergots; ergots taken on a daily basis, when stopped, cause a rebound headache 5. Pain accompanied by serious adverse reactions or complications from therapy; continued use of such therapy aggravates pain 6. Pain in the presence of significant medical disease; appropriate treatment of headache symptoms aggravates or induces further illness 7. Chronic cluster headache unresponsive to treatment 8. Treatment that requires co-pharmacy with drugs that may cause a drug interaction and necessitates careful observation within a hospital environment (monoamine oxidase inhibitors and beta-blockers) 9. Patients with probable organic cause of their hcadaches, requiring the appropriate consultations and perhaps neurosurgical intervention

563

MIGRAINE HEADACHES

zation may be required for a variety of reasons (Table 4). A multidiseiplinary approach to headache therapy is utilized, with a special emphasis on patient education. As stated previously, withdrawal from habituating agents, as well as initiation of eo-pharmacy, is best achieved in an inpatient setting.

SUMMARY Once the definitive diagnosis of migraine has been formulated, the physician has many options available for abortive and prophylactic therapy. Nonpharmacologic modalities, including behavioral modification methods such as biofeedback training, may also be considered. ~igraine does not necessarily have to disrupt the lives of those afflicted. The patient with mixed headache presents a more difficult diagnostic and therapeutic problem. These patients can also be helped when the disorder is identified, and inpatient therapy for these patients may be required.

REFERENCES 1. Anthony M, Lance JW: Monoamine oxidase inhibition in the treatment of migraine. Arch NeuroI21:263-268, 1969 2. Aring CD: The migrainous scintillating scotoma. JAM A 220:519-522, 1972 3. Ashford JW, Ford CV: Use of MAO inhibitors in elderly patients. Am J Psychiatry 136:1466-1477, 1979 4. Bille B: The development of pediatric headache research. Headache Quarterly 1:39-42, 1990 5. Bille B: Migraine in school children. Acta Paediatr Scand 51:1-151, 1962 6. Blau IN, Diamond S: Dietary factors in migraine precipitation: the physician's view. Headache 25:184-187, 1985 7. Couch JR, Hassanein RS: Amitriptyline in migraine prophylaxis. Arch Neurol 36:695699, 1979 8. Couch JR, Ziegler DK, Hassanein R: Amitriptyline in the prophylaxis of migraine. Neurology 26:121-127, 1976 9. Critchley M: Discarded theories in the past 50 years. In Blau IN (ed): Migraine: Clinical and Research Aspects. Baltimore, The Johns Hopkins University Press, 1987, pp 241246 10. Dalessio DJ, Kunzel M, Sternbach R, et al: Conditioned adaptation-relaxation reflex in migraine therapy. JAMA 242:2102-2104, 1979 11. Dalton K: Migraine and oral contraceptives. Headache 15:247, 1975 12. Diamond S: Inpatient treatment of headache. Clin J Pain 5:101-103,1989 13. Diamond S: Migraine headache: Its diagnosis and treatment. Clin J Pain 5:3-9, 1989 14. Diamond S: Depression and headache. Headache 23:122-126, 1983 15. Diamond S: The psychiatric aspects of headache. In Cochrane AL (ed): Background to Migraine. New York, Springer-VerJag, 1970, pp 60-64 16. Diamond S: Depressive headaches. Headache 4:255-259, 1964 17. Diamond S, Dalessio DJ: Classifications and mechanisms of headache. In Diamond S, Dalessio DJ (eds): The Practicing Physician's Approach to Headache, ed 4. Baltimore, Williams & Wilkins, 1986, pp 1-10 18. Diamond S, Dalessio DJ: Migraine headache. In Diamond S, Dalessio DJ (eds): The Practicing Physician's Approach to Headache, ed 4. Baltimore, Williams & Wilkins, 1986, pp 44-65 19. Diamond S, Freitag FG: The use of fluoxetine in the treatment of headache [letter]. Clin J Pain 5:200-201, 1989 20. Diamond S, Freitag FG, Diamond ML: Flunarizine in migraine therapy [abstract]. Clin Pharmacol Ther 47:165, 1990 21. Diamond S, Freitag FG, Gallagher RM, et al: Ketoprofen in the prophylaxis of migraine. Headache 1:75-77, 1990

564

SEYMOUR

DIA~lOND

22. Diamond S. Freitag FC, Nursal A: The effects of weather on migraine frequency in Chicago. Headache Quarterly 1:136-145, 1990 23. Diamond S, Freitag FC, Prager J, et al: Olfactory aura in migraine [letter]. N Engl J Med 312(21):1390-1391, 1985 24. Diamond S, Montrose D: The value of biofeedback in the treatment of chronic headache: A four-year retrospective study. Headache 24:5-18, 1984 25. Diamond S, Prager J, Freitag FC: Diet and headache: Is there a link? Postgrad Med 79:279-286, 1986 26. Diamond S, Schenbaum H: Flunarizine, a calcium channel blocker, in the prophylactic treatment of migraine. Headache 23:39-42, 1983 27. Diamond S, Solomon CD: Pharmacologic treatment of migraine. Rational Drug Ther 22:1-5, 1988 28. Diamond S, Solomon CD, Freitag FC, et al: Fenoprofen in the prophylaxis of migraine: A double-blind, placebo-controlled study. Headache 27:246-249, 1987 29. Diamond S, Solomon CD, Freitag FC, et al: Long-acting propranolol in the prophylaxis of migraine. Headache 27:70-72, 1987 30. Diener HC, Dichgans J, Scholz E, et al: Analgesic-induced chronic headache: Long-term results of withdrawal therapy. J Neurol 236:9-14, 1989 31. Doezicke A, Melchart D, Bayliss EM: Effective improvement of symptoms in patients with acute migraine by CR43175 administered in dispersible tablets. Cephalalgia 9 (suppl 9):89-92, 1989 32. Edmeads J: Cerebral blood flow in migraine. Headache 17:148-152, 1977 33. Fere C: Contribution a l'etude de la migraine ophthalmique. Rev Med 1:625-649, 1881 34. Friedman AP: The migraine syndrome. Bull NY Acad Med 44:45-62, 1968 35. Freitag FC, Diamond S, Solomon CD: Antidepressants in the treatment of mixed headache: MAO inhibitors and combined use of MAO inhibitors and tricyclic antidepressants in the recidivist headache patient. In Rose FC (ed): Advances in Headache Research. London, John Libbey, 1987, pp 271-275 36. Callagher RM, Stagliano RA, Sporazzo C: Timolol maleate, a beta-blocker, in the treatment of common migraine headache. Headache 27:84-86, 1987 37. Carvey MJ, Tollefson CD, Schaffer CB: Migraine headaches and depression. Am J Psychiatry 141:986-988, 1984 38. Celmers HJ: Nimodipine, a new calcium antagonist, in the prophylactic treatment of migraine. Headache 23:106-109, 1983 39. Cowers W: In Diseases of the Nervous System, vol 2. Philadelphia, Blakiston Son & Co, 1893, pp 836-866 40. Henryk-Cutt R, Rees WL: Psychological aspects of migraine. J Psychosom Res 44:652, 1973 41. Isler H: Retrospect: The history of thought about migraine from Aretaeus to 1920. In Blau IN (ed): Migraine: Clinical and Research Aspects. Baltimore, The Johns Hopkins University Press, 1987, pp 659-674 42. Johannson V, Nilsson LR, Widelius T, et al: Atenolol in migraine prophylaxis: a doubleblind cross-over multicentre study. Headache 27:372-374, 1987 43. Johnson ES, Ratcliffe DM, Williamson M: Naproxen sodium in the treatment of migraine. Cephalalgia 5:5-10, 1985 44. Kangasniemi P, Andersen AR, Andersson PC, et al: Classic migraine: Effective prophylaxis with metoprolol. Cephalalgia 7:231-238, 1987 45. Lance JW, Curran DA: Treatment of chronic tension headache. Lancet 1:1235-1239, 1964 46. Langohr HD, Cerber WD, Kdetzki E, et al: Clomipramine and metoprolol in migraine prophylaxis-a double-blind crossover study. Headache 25:107-113, 1985 47. Leao AP: Spreading depression of activity in the cerebral cortex. J Neurophysiol (Lond) 7:359-390, 1944 48. Linet MS, Stewart WF: Migraine headache: Epidemiologic perspectives. Epidemiol Rev 6:107-139, 1984 49. Linet MS, Stewart WF, Celentano DD, et al: An epidemiologic study of headache among adolescents and young adults. JAM A 261:2211-2216, 1989 50. Liveing E: In On Megrim, Sick Headache and Some Allied Disorders. London, Churchill Livingstone, 1873

MIGRAINE HEADACHES

565

51. Loew DM, van Deusen ER, Meier WR: In Ergot Alkaloids and Related Compounds. New York, Springer-VerJag, 1978, pp 421-439 52. Mahloudji M: Prevention of migraine. Br Med J 1:182-183,1969 53. Mathew NT: Prophylaxis of migraine and mixed headache: A randomized controlled study. Headache 21:105-109, 1981 54. Mathew NT, Stubits E, Nigam MP: Transformation of episodic migraine into daily headache: Analysis of factors. Headache 22:382-383, 1982 55. Medina JL, Diamond S: Cyclical migraine. Arch Neurol 38:341-344, 1981 56. Merikangas KR, Risch NJ, Merikangas JR, et al: Migraine and depression: Association and familial transmissions. J Psychosom Res 22:119-129, 1988 57. Meyer JS, Dalessio DJ: Toxic vascular headache. In Dalessio DJ (ed): Wolffs Headache and Other Head Pain, ed 5. New York, Oxford University Press, 1987, pp 136-171 58. Morland TJ, Starli OV, Mogstad TE: Doxepin in the prophylactic treatment of mixed "vascular" and tension headache. Headache 19:382-383, 1979 59. Nestvold K: Naproxen and naproxen sodium in acute migraine attacks. Cephalalgia 6 (suppl 4):81-84, 1986 60. Nestvold K, Kloster R, Partinen M, et al: Treatment of acute migraine attack: naproxen and placebo compound. Cephalalgia 5:115-119, 1985 61. Nielsen TH, Tfelt-Hansen P: Lack of effect of CR43175 on peripheral arteries in man. Cephalalgia 9 (suppl 9):93-95, 1989 62. Noone JR: Psychotropic drugs and migraine. J Int Med Res R:66-67, 1977 63. Olesen J: Classification and diagnostic criteria for headache disorders, cranial neuralgias, and facial pain. Cephalalgia 8 (suppl 7):9-96, 1988 64. Olesen J, Larsen B, Lauritzen M: Focal hyperemia followed by spreading oligemia and impaired activation of rCBF in classic migraine. Ann Neurol 9:344-352, 1981 65. Olesen J, Lauritzen M, Tfelt-Hansen P, et al: Spreading cerebral oligemia in classical and normal cerebral blood flow in common migraine. Headache 22:242-249, 1982 66. Pare CMB, Hallstrom C, Kline N, et al: Will amitriptyline prevent the "cheese" reaction of monoamine oxidase inhibitors? Lancet 2:183-186, 1982 67. Peatfield RC, Rose FC: Migrainous visual symptoms in a woman without eyes. Arch NeuroI38:466, 1981 68. Peroutka SJ, Banghart SB, Alien CS: Relative potency and selectivity of calcium antagonists used in the treatment of migraine. Headache 24:55-58, 1984 69. Pfaffenrath V, Kellhammer U, Poll man W: Combination headache: Practical experience with a combination of a beta blocker and an antidepressive. Cephalalgia 6:25-31, 1986 70. Phillips C: Headaches and personality. J Psychosom Res 20:535-542, 1976 71. Pradalier A, Clap in A, Dry J: Treatment review: Non-steroidal anti-inflammatory drugs in treatment and long-term prevention of migraine attacks. Headache 28:550-557, 1988 72. Prusinski A: Monotherapy or poly therapy in migraine. Neuroepidemiology 6:186-189, 1987 73. Raskin NH, Raskin KE: Repetitive intravenous dihydroergotamine for the treatment of intractable migraine. Neurology 34 (suppl 1):245, 1984 74. Robinson DS: MAOls and the elderlv. In Friedman E, Mann J, Cershon S (eds): Depression and Antidepressants: Implications for Cause and Treatment. New York, Plenum Press, 1981 75. Ross WO, McNaughton FL: Objective personality studies in migraine by means of the Rohrschach method. Psychosom Med 2:23, 1945 76. Ryan RE, Ryan RE Jr: Clonidine: Its use in migraine therapy. Headache 14:190-192, 1975 77. Sacks 0: In Migraine: Evolution of a Common Disorder. London, Faber and Faber, 1970, p 26 78. Sakai F, Meyer JS: Regional cerebral hemodynamics during migraine and cluster headache measured by the 133 xenon inhalation method. Headache 18:122-132, 1978 79. Sargent J, Baumel B, Peters K, et al: Aborting a migraine attack: Naproxen sodium v. ergotamine plus caffeine. Headache 28:263-266, 1988 80. Sargent J, Solbach P, Damasio H, et al: A comparison of naproxen sodium to propranolol hydrochloride and a placebo control for the prophylaxis of migraine headache. Headache 25:320-324, 1985 81. Schuckit M, Robins E, Feighner J: Tricyclic antidepressants and monoamine oxidase

566

82. 83. 84. 85. 86. 87. 88. 89. 90. 91. 92. 93. 94. 95. 96. 97. 98.

SEY\10UR DIAMOND

inhibitors: Combination therapy in treatment of depression. Arch Gen Psychiatry 24:509-514, 1971 Selby G, Lance JW: Observations on 500 cases of migraine and allied vascular headache. J Neurol Neurosurg Psychiatry 23:23, 1960 Skyhoj Olsen T: Migraine with and without aura: The same disease due to cerebral vasospasm of different intensity. A hypothesis based on CBF studies during migraine. Headache 30:269-272, 1990 Skyhoj Olsen T, Friberg L, Lassen NA: Ischemia may be the primary cause of the neurological deficits in classic migraine. Arch NeuroI44:156-161, 1987 Skyhoj Olsen T, Lassen NA: Blood flow and vascular reactivity during attacks of classic migraine. Limitations of the Xe-133 intra-arterial technique. Headache 29:15-20, 1989 Solomon GD: The use of calcium-channel blockers in migraine. In Diamond S (ed): Migraine Headache: Prevention and Management. New York, Marcel Dekker, 1990, pp 99-125 Solomon CD, Diamond S: Verapamil in migraine prophylaxis: Comparison of dosages. Clin Pharmacol Ther February:202, 1987 Solomon GD, Spaccavento LJ: Verapamil prophylaxis of migraine: A double-blind, placebo-controlled trial. JAMA 250:2500-2502, 1983 Speight TM, Avery GS: Pizotifen (BClO5): A review of its pharmacological properties and its therapeutic efficacy in vascular headache. Drugs 3: 153, 1972 Sudilovsky A, Elkind AH, Ryan RE Sr, et al: Comparative eflicacy of nadolol and propranolol in the management of migraine. Headache 27:421-426, 1987 Tfelt-Hansen P, Brand J, Dano P, et al: Early clinical experience with subcutaneous GR43175 in acute migraine: An overview. Cephalalgia 9 (suppl 9):73-77, 1989 Welch KMA: Naproxen sodium in the treatment of migraine. Cephalalgia 6:85-92, 1986 White D, Simpson G: Combined MAOI-tricyclic antidepressant treatment: A reevaluation. J Clin Psychopharmacol 1:264-282, 1981 Wolff HG: In Headache and Other Head Pain, ed 2. New York, Oxford University Press, 1963 Wolff HG: Personality features and reaction of subjects with migraine. Arch Neurol Psychiatry 37:895, 1937 Ziegler DK, ElIis DJ: Naproxen in prophylaxis of migraine. Arch Neurol 42:583-584, 1985 Ziegler DK, Hurwitz A, Hassanein RS, et al: Migraine prophylaxis: A comparison of propranolol and amitriptyline. Arch Neurol 44:486-489, 1987 Ziegler DW: The treatment of migraine. In Dalessio DJ (ed): Wolff's Headache and Other Head Pain, ed 5. New York, Oxford University Press, 1987, pp 87-111

Address reprint requests to Seymour Diamond, MD Diamond Headache Clinic 5252 North Western Avenue Chicago, IL 60625