CONQUERING HEADACHE

Sixth Edition

An Illustrated Guide to Understandingthe Treatment and Control of Headache

ALAN M. RAPOPORT, MDFRED D. SHEFTELL, MDSTEWART J.TEPPER, MD

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© 2008 Alan M. Rapoport, Fred D. Sheftell, and Stewart J. Tepper

First edition, 1995. Second edition, 1998. Third edition, 2001. Fourth edition, 2003.Fifth edition, 2004.

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Notice: The authors and publisher have made every effort to ensure that the patient carerecommended herein, including choice of drugs and drug dosages, is in accord with the acceptedstandard and practice at the time of publication. However, since research and regulationconstantly change clinical standards, the reader is urged to check the product information sheetincluded in the package of each drug, which includes recommended doses, warnings, andcontraindications. This is particularly important with new or infrequently used drugs. Anytreatment regimen, particularly one involving medication, involves inherent risk that must beweighed on a case-by-case basis against the benefits anticipated. The reader is cautioned that thepurpose of this book is to inform and enlighten; the information contained herein is notintended as, and should not be employed as, a substitute for individual diagnosis and treatment.

We would like to thank our patients and colleagues, who havehelped us to learn and understand the information in thisbook.We would also like to thank the pharmaceutical industryfor its generosity in funding clinical research and physicianeducation, both of which lead to greater understanding ofheadache and more effective treatment for our patients.

To my entire family, including Arja, my wife of 41 years, my 3 children TJ, Mark and Sabrina, their spouses, and my fourcurrent and all future grandchildren: my thanks to all of youfor consistently supporting my long-time efforts to helpadvance headache medicine around the world.To my patients:my thanks for having entrusted me with your care.

Alan Rapoport

In loving memory of my father, Joe Sheftell; the courage andstrength of my mother Wilma; for my wife Karen, withoutwhose support I might never had made the journey, and ourchildren, Jason and Lauren, for making it fun; and to my patients,who have taught me so much about dignity and courage.

Fred Sheftell

To my family,without whose patience this book could not havehappened. To my friends and colleagues, Alan Rapoport andFred Sheftell,my partners and mentors for eight years,who wel-comed me, taught me, helped me, and treated me with love andrespect. I am grateful and honored to call them my friends andto have had the good fortune to have worked with them.

Stew Tepper

iii

ACKNOWLED GMENTS

DED ICAT IONS

Preface . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . vii

1. History of Headache . . . . . . . . . . . . . . . . . . . . . . . . 1

2. Impact of Headache on Society . . . . . . . . . . . . . . . . 3

3. Types of Headache . . . . . . . . . . . . . . . . . . . . . . . . . 7

4. Causes of Headache . . . . . . . . . . . . . . . . . . . . . . . . 22

5. Danger Signals . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34

6. The Doctor’s Role . . . . . . . . . . . . . . . . . . . . . . . . . 36

7. Psychological Factors . . . . . . . . . . . . . . . . . . . . . . . 39

8. Medication-Overuse Headache (Rebound Headache) 44

9. Acute Treatment of Attacks with Medication . . . . . . 51

10. Preventive Treatment of Migraine with Medication . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 80

11. Treatment of Cluster Headache with Medication . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 93

12. Treatment without Medication . . . . . . . . . . . . . . . . 99

13. Patient-Doctor Relationship . . . . . . . . . . . . . . . . . . 112

14. Emergency Department and Hospital Treatment . . . . 114

15. Headache in Children . . . . . . . . . . . . . . . . . . . . . . . 119

16. Hormones and Headache in Women . . . . . . . . . . . . 128

17. Travel, Holidays, and Headache . . . . . . . . . . . . . . . . 138

A Final Word . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 144

Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 145

v

CONTENTS

This most recent edition of Conquering Headache, an ongo-ing labor of love, is intended to update our readers with theongoing changes in the field of headache. This past year hasseen the initiation of a nationwide effort spawned by DrRobert Shapiro of the University of Vermont called“Headache on the Hill,” where experts joined with sufferers inlobbying Congress to increase funding by the National Insti-tutes of Health for research in the field of headache and makeparity with other disabling disorders. Watch for developmentsin this area and fundraising events throughout the UnitedStates. It is only through research that we can improve thestate-of-the-art knowledge about headache, its prevalence,impact, mechanisms and treatments, and thus improve thequality of life for the many sufferers in our nation.

The new edition includes updated information on menstrualmigraine, mechanisms of migraine, and daily headache, amongother areas. We hope that this book will serve as a guide tohelp patients and care providers to work out an accurate diag-nosis and treatment plan together.

Alan Rapoport, MDFred Sheftell, MDStewart Tepper, MDDecember 2007

vii

PREFACE

viii

The experience of headache has been around as long as thehuman race. Our ancestors believed that headache was visitedon us as punishment for offending the gods or that it occurredwhen humans became possessed by evil spirits. Through theages, treatment has been directed at the suspected cause;not sur-prisingly, headache remedies were aimed at ridding the bodyof demons.Thus, the earliest neurosurgeons bored holes in theskull through which the headache-causing demons could es-cape. Skulls with evidence of such surgery (called trephination)have been found in Peru anddate back to the thirteenthcentury (Figure 1-1).

Hippocrates, a physicianwho practiced in ancientGreece, noticed that vomit-ing ended some attacks ofhead pain, so he prescribedherbs to cause vomiting. Healso used another treatment:the application of leeches orbloodletting through smallcuts, a practice that persistedthrough the Middle Ages.Theancient Egyptians wrappedthe heads of sufferers in linenalong with a clay crocodileholding in its mouth wheatfrom the gods’ storehouse(Figure 1-2).

In the seventeenth cen-tury, Thomas Willis theo-

1

HISTORY OF HEADACHE

CHAPTER 1

Figure 1-1: Slash marks crisscrossa gaping hole in a twelfth or thir-teenth century Peruvian girl’s skull.The hole shows no signs of boneregrowth, so the girl likely died asa result of her operation. Repro-duced with permission from theNational Museum of Natural His-tory, Washington, DC, catalogue#178473.

rized that headache painwas related to swollen bloodvessels in the head. ErasmusDarwin, Charles Darwin’sgrandfather, further exploredthese theories. Interestingly,both Charles and ErasmusDarwin suffered from mi-graine headache.

In the late nineteenthcentury, an English neurolo-gist named Liveing was thefirst doctor to write thatheadaches, like seizures,were“nerve storms,” affecting thenerves of the head more thanthe blood vessels.

Folk remedies such as tying rags around the head or apply-ing tobacco stamps to the head had their advocates, as doherbal remedies still. Heat, cold, acupuncture, chiropracticmanipulation, nerve blocks, diets, laser therapies, hyperbaricoxygen, and hysterectomies have also been proposed asheadache treatments.There is no shortage of conflicting opin-ion and information, adding to headache sufferers’ confusionabout which treatments may help.

It is generally not possible to completely cure yourheadache.What you can expect is fewer headaches and bettercontrol of the pain.The remainder of this book tells you howto take control of your headaches.

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Figure 1-2: Egyptian with a claycrocodile with herbs in its mouthplaced on his head for headachetreatment. Courtesy of JohnEdmeads, MD.

More patients who visit doctors complain of headachethan of any other single ailment.Yet migraine—and headachein general—continues to be underdiagnosed, misdiagnosed,and mistreated or undertreated. Recent studies show thatslightly more than half of migraineurs have not been diag-nosed with migraine by a physician. If patients do not have thediagnosis of migraine, they will not get the proper treatmentfor it.Although medical students and even neurology residentsin the hospital learn a great deal about serious causes ofheadache, such as tumors, strokes, aneurysms, and meningitis,they do not learn much about migraine and tension-typeheadache, the types they will see most frequently in theiroffices.

In the past several years, some off-the-shelf pain relievershave been approved by the US Food and Drug Administrationas effective for migraine or “migraine pain,” and manufacturershave been allowed to advertise on television and in newspa-pers and magazines. These medications, such as ExcedrinMigraine, Advil Migraine, and Motrin Migraine Pain, can beeffective when used infrequently for mild attacks. However,because they are available without prescription, the manufac-turers do not have to provide a safety warning in the adver-tisements, even though the medications can cause majorproblems.We warn our patients taking off-the-shelf painkillersto be aware of gastrointestinal symptoms, heartburn, stomachulcers, long-term liver or kidney problems, easy bruisability,and the development of daily headache (analgesic reboundheadache, also called chronic migraine with medication overuse).

Headaches may occasionally be due to allergies or sinusproblems, but the majority of patients with allergies do notusually get headaches from them. Acute sinus infections can

3

IMPACT OF HEADACHE ON SOCIETY

CHAPTER 2

make someone very sick and cause a headache, but peoplewith frequent headaches in the sinus area who think thatchronic sinus problems are the cause of their headaches usu-ally, in fact, have migraine. A recent study found that of over2,500 patients who thought that they had sinus headache,more than 90% had migraine headache. In addition, manypeople who worry that their headaches result from psycholog-ical factors seek treatment for sinus and allergy problems,which they would rather believe are the cause of theirheadaches.

The bulk of nonprescription pain medication is consumedby migraine sufferers and people with chronic daily headache.Headache sufferers are the main purchasers of the 20,000 tonsof acetylsalicylic acid (ASA; Aspirin), plus much of the aceta-minophen (Tylenol), ibuprofen, and other anti-inflammatoryand sinus medications, consumed yearly in the United States.Lacking a proper diagnosis, these individuals rely on off-the-shelf medicines because they have never received a prescrip-tion for a migraine-specific medication.

Until the middle of the twentieth century, over the countermeant that you could ask your pharmacist for a bottle ofAspirin, for example, and he or she would personally give it toyou, over the counter.Today, only prescription medications arepassed over the counter; nonprescription medicines are pur-chased off the shelf and are available in pharmacies, conveniencestores, supermarkets, and gas stations (Figure 2-1).

As noted above, if nonprescription medication is usedimproperly, it can have serious consequences. When overused,ASA (Aspirin), specifically, and Excedrin Migraine and Anacin,both of which contain ASA, can cause or aggravate pepticulcer, irritation of the stomach (gastritis), bleeding, bruising,ringing in the ears (tinnitus), and kidney damage; ASA canalso aggravate asthma. Similarly, ibuprofen (Advil Migraine andMotrin Migraine Pain) can cause ulcers, bleeding, and kidney

4

damage, and acetaminophen(Tylenol) can cause liverdamage. Additionally, manysinus and allergy prepara-tions contain ingredientsthat can increase your bloodpressure.

At our headache centerin Stamford, CT, we fre-quently see patients whotake 8 to 12 tablets per dayof various off-the-shelf products.When the stronger prescrip-tion medications for headache are taken too frequently, theproblem becomes worse.The more frequently a pain medica-tion is taken, the greater is the risk of causing chronic severeheadaches that respond poorly to all treatments. So, althoughoff-the-shelf pain relievers and other medications targeted forheadache can be effective when used properly for occasionalheadaches, overuse can result in headaches that are harder totreat, more painful, and more constant.These are called anal-gesic rebound headaches, rebound headaches, or chronic migraine withmedication overuse (see Chapter 8).

The impact of headache on our society is enormous;migraine is truly a hidden epidemic.A Canadian survey showsthat 92% of migraine sufferers have disability that ranges fromdiminished ability to function to requiring bed rest. Art cre-ated by headache sufferers has shown how headache can affectevery aspect of their lives. Migraine victims feel isolated fromthe world around them at work, school, home, and play.Headache is the leading cause of absenteeism from the work-place and accounts for the loss of some 150 million work daysper year in the United States alone; the cost of lost labor hoursis estimated to be as high as 17 billion dollars (US) each year.Headache can also disrupt every aspect of life outside the

5

Figure 2-1: Some off-the-shelf painmedications purchased withoutsupervision.

workplace and—in an era when some medical costs are notadequately covered by insurance companies—can result inunnecessary medical expense if misdiagnosed or inadequatelytreated.

Society may not understand headache or its impact onthose who suffer from it.Workers who telephone their bossesor coworkers to say that they cannot come to work because ofa headache may be considered malingerers, or worse. Theclaim of disability because of “the flu” is more believable, andthe claim of a broken bone is never questioned.Valerie South,formerly of the International Headache Society, points outthat “migraine is more than just a ‘headache’; [it] is a debilitat-ing disorder of the central nervous system.” Our mission is toeducate you about headache so that you can improve yourquality of life and thereby decrease the impact of headache onyou and your family. If you are one of the many migraine suf-ferers who have significant disability from migraine, this willbe your first step toward decreasing the level of that disabilityand improving your functioning.

6

Headaches have been classified according to their character-istics to provide a common language for doctors and patientsto use when talking about them. All headaches can be classi-fied as either primary or secondary.The secondary headachedisorders are those caused by an underlying medical problem.Serious causes of secondary headache include brain tumors,bleeding in the brain, aneurysms (weakened blood vesselwalls), and infections. Less serious causes of secondaryheadache include dental problems, temporomandibular joint(TMJ) syndrome, eye problems, true sinus infections, neckproblems, and allergies.Although television commercials focuson allergies and sinus problems as causes of headache, the mostcommon types of headaches are the primary headaches, whosecauses are often not known.These are headaches not attribut-able to some other medical problem. The primary headachedisorders fall into three main categories: (1) migraine, (2) ten-sion-type headache, and (3) cluster headache (Table 3-1).

MIGRAINE: WHAT IS IT?

Migraine is a headache that usually occurs in discrete (sepa-rate) episodes, but can become daily, and has an impact on

7

TYPES OF HEADACHE

CHAPTER 3

Table 3-1: Major Headache Disorders

Disorder Prevalence (%)Primary headache

Migraine 12Women 18Men 6

Tension-type headache 70–90Cluster < 0.1

Secondary headache (organic) < 1

patients in terms of affecting work, home, school, or recre-ational activities. Migraine is associated with features such asworsening with routine physical activity, nausea, or dislike oflight and noise (see below).

Migraine occurs three times more commonly in womenthan in men, often causing disability, and it affects about 10 to15% of the world’s population. Most people with migrainehave their first episode of headache between the ages of 6 and25. Migraine occurs slightly more often in boys than in girlsuntil the age of 11 or 12.After the onset of puberty, when girlsstart to menstruate, there is a higher incidence of migraine ingirls and women. The two major categories of migraine aremigraine without aura (previously called common migrainebecause it is the most common type) and migraine with aura(previously called classic migraine, which only about 30% ofmigraineurs ever experience). Migraine is usually inherited.Parents with migraine whose children complain of headacheshould not assume that their children are imitating them. Chil-dren of migraine sufferers who complain of headaches shouldbe believed and evaluated by a doctor. Headache may begin asearly as age 2. If one parent has migraine, there is about a 40%chance that each child will have it; if both parents havemigraine, there is at least a 75% chance that each child willexperience migraine.

Migraine without Aura (Formerly Called Common Migraine)A simplified way of recognizing migraine occurring inepisodes is becoming popular with primary care physicians:any patient with a stable pattern over at least 6 monthsof intermittent, severe headache in discrete episodesthat causes considerable disability or results in losttime from work, home, school, or recreational activi-ties, which resolves within 24 to 48 hours, with noworsening over time, has migraine until proven other-

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wise (Table 3-2). Headache specialists also use specific criteriato make a diagnosis of migraine without aura: at least five pre-vious attacks should have occurred, underlying medical condi-tions or serious causes that could mimic migraine must beruled out, and attacks must last for 4 to 72 hours, with anaverage attack lasting from 12 to 48 hours.

With these criteria present, the diagnosis of migraine with-out aura then requires the presence of two of the four group 1diagnostic characteristics and one of the three group 2 charac-teristics shown in Table 3-3. If a person is missing just one ofthe criteria for migraine, this is called probable migraine, ormigrainous disorder, but this is considered just another form ofmigraine and is treated as such. Other symptoms of a migraineattack may include dizziness, frequent urination, diarrhea,sweating, tearing, and cold hands and feet.We describe some“red flags” in Chapter 5 that help you determine when to beconcerned about other causes of headache. For example, if a

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Table 3-2: Proposed Simplif ied Diagnosis of Migraine

A stable pattern of intermittent moderate to severe headache that causes somedisability, with return to normal within 48 hours and no worsening over time, ismigraine until proven otherwise.

Table 3-3: Diagnostic Characteristics of Migraine without Aura

Group 1 (two of four)Headache on one side of the headThrobbing or pulsating painModerate to severe pain that makes it difficult or impossible to functionWorsening of pain in response to routine physical activity such as bending over

or climbing stairsGroup 2 (one of three)

NauseaVomitingSensitivity to both light and sound

fever is present with your headache, you must contact a doctorto rule out a serious infection such as meningitis. High bloodpressure during a migraine attack may just be because of thepain, but it may be dangerous to take a triptan or other med-ications when your blood pressure is high.To be on the safeside, have your blood pressure checked between headaches tomake sure it has returned to normal levels (eg, 110–120/70–80mm Hg) and to be certain that you do not have high bloodpressure, which must be treated. Many patients with an acutemigraine attack retreat to a dark quiet room and lie very still;sleep may help to end a migraine attack. Cold compresses tothe forehead, temples, or back of the neck may also be helpful.

Migraine with Aura (Formerly Called Classic Migraine)Aura refers to symptoms that are usually visual and occur beforeor at the same time as the headache. In fact, the word aura meanswind.Approximately 15 to 30% of patients with migraine experi-ence the warning phenomenon of aura with some or all of theirheadaches. Headache that follows aura is similar to that previ-ously described but is often less intense and not as difficult totreat. Some patients have aura without the subsequent headache;this is known as a migraine equivalent or aura without headache.Thisdoes not have to be treated unless the auras are very frequent.Auras usually last for 20 to 30 minutes.The most common typesof visual auras are multicolored spots, flashing bright lights (pho-topsia),or bright-edged shimmering zigzag lines in the shape of acrescent (Figure 3-1). This shape can grow in size and moveslowly across the visual field. Other visual disturbances include ascotoma (a small growing black or colorless area in the visualfield) that obscures vision, loss of vision on one or both sides, tun-nel vision, or inability to see words in a particular area whenlooking at a printed page. Some auras include neurologic eventsthat can resemble stroke symptoms, such as weakness or numbnessin an arm and/or leg on one side, difficulty speaking or thinking,coordination problems, or even loss of consciousness. If aura

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symptoms persist for more than 1 hour, they could be related to amore serious abnormality in the brain. Typically, the headachefollows the aura either immediately or within 60 minutes.

MENSTRUAL MIGRAINE

Migraine occurring around menses is referred to as menstrualmigraine. Menstrual migraine has the same characteristics asmigraine occurring the rest of the month.The fact that womencan predict when the migraine is going to come offers thera-peutic options, but the headache type is the same as non-men-strual migraine. Some studies indicate that menstrual migraine ismore severe, more prolonged, and more difficult to treat thannon-menstrual migraine. Migraines occurring from 2 daysbefore menstrual flow to 3 days into flow, but occasionallyoccurring the rest of the month are called menstrually–relatedmigraines.Migraines that occur only during menstrual flow andnever occur the rest of the month are called pure menstrualmigraine (please see Chapter 16 for more on this topic).

TENSION-TYPE HEADACHE: WHAT IS IT?

Tension-type headache is the most common type of headache.Probably 90% or more of the world’s population has experi-

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Figure 3-1: Visual aura: changes in vision prior to migraine pain.

enced one from time to time.Many of these headaches are asso-ciated with tension in muscles in the head, face, jaw, or neck,although this may not be the case in some patients. There ismuch speculation as to whether tension-type headache andmigraine headache are separate disorders. Many headache spe-cialists believe that they are caused by similar mechanisms in thebrain, and most patients who experience one also experiencethe other. Tension-type headache may be episodic (occurringonce in a while) or chronic (occurring most days of the month).

Episodic Tension-Type HeadacheOccurring occasionally—once or twice per week or once permonth—episodic tension-type headaches are described as amild pressing, aching, squeezing sensation, or tight bandaround the head that does not throb or pound.They are usu-ally felt on both sides of the head. Unlike migraine, the pain isoften mild or moderate, does not interfere with normal func-tion, and is not aggravated by activity.These headaches are notassociated with nausea; however, light or sound sensitivity maybe present, but not both.

Chronic Tension-Type HeadacheSymptoms of chronic tension-type headache are identical tothose of the episodic variety. However, chronic tension-typeheadache occurs on more than 15 days per month, usuallyalmost daily. Many patients have had these symptoms formonths or years when they first visit our office. They ofteneventually develop chronic daily headache, with pain on andoff throughout each day. Tension-type headache is reallydefined by what it is not; it is not migraine; it is a featurelessheadache.Tension-type headache, because it is not associatedwith an impact on lifestyle or disability, does not bring apatient into the doctor’s office. Notice that tension-typeheadache is not defined by a location in the neck or the sideor back of the head. Headaches significant enough to cause

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disability and lost time from life, but occurring in these loca-tions, usually turn out to be migraine. So do not let the loca-tion of pain or its triggers alone determine your diagnosis!

CLUSTER HEADACHE

Cluster headache is probably the most dramatic of all of theheadache types.There are two categories of cluster headache:episodic cluster, which is more common (about 90% of cases),and chronic. Episodic cluster occurs for about 4 to 8 weeksand then disappears, often for about a year. In this clusterperiod, the patient experiences attacks about 1 to 3 times perday. Cluster periods may occur every 1 to 2 years or onlyonce in a lifetime. Chronic cluster continues for years, andattacks occur at least several times per week.The pain of clus-ter headache occurs exclusively on one side of the head, inand around the eye and temple. In contrast to typical throb-bing migraine pain, cluster pain is more steady, boring, andrelentless. Patients describe the pain as an intense pressurebehind the eye that feels as though it is pushing the eye for-ward out of the socket. Some patients describe the feeling asone that makes them want to pluck out the painful eye. Oth-ers describe it as a red-hot poker being thrust into the eyewith immense force and then twirled. Drooping of the eyelid,constriction of the pupil, and redness and tearing of the eye,followed by a stuffed then running nostril, may accompanythe headache, all occurring on the same side of the head asthe pain.The average duration of the pain is 45 to 90 minutes,but it may last anywhere from 20 minutes to 3 hours.Attacksmay occur several times per day, with an average of one tothree attacks in a 24-hour period. Cluster headaches oftenoccur at the same time of the day or night, almost like clock-work, usually after work. Most characteristically, theseheadaches awaken the sufferer 90 minutes after falling asleep.Patients notice that if they nap during the day, they awaken

13

with a headache. In contrast to migraine, which affects one infive women and occurs three times more frequently inwomen than in men, cluster headache occurs three times asoften in men and affects less than 0.1% of the population. Afamily history of cluster headache is much less common thanit is with migraine.The typical sufferer is a 35-year-old male,a little taller than average, who may have hazel-colored eyesand deep lines around the forehead, mouth, and chin. Clusterpain is so excruciating that it brings even the strongest ofmen to their knees. It is no wonder that cluster headache hasbeen termed suicide headache. Rather than retreat to a darkquiet room, as migraine sufferers do, cluster patients cannot sitor lie still. Rather, they pace, rock, and drive their fists into thepainful eye. Some patients may even show unusual behavior,such as hitting themselves in the head, banging their headsagainst the wall, or engaging in intense physical activity suchas push-ups or running.The word cluster describes the timingpattern of these headaches, which occur in cluster periods ofabout 4 to 8 weeks per year. Patients are free of headachebetween cluster periods.Alcohol is the most common trigger,but only during the cluster period. Frequent drinkers of alco-hol may stop drinking completely until the cluster period haspassed. Symptoms and signs of cluster headache may misleaddoctors to incorrect diagnoses, such as sinus headaches, andinappropriate treatments, such as a variety of sinus medica-tions and surgery.They may also be mistaken for dental prob-lems or TMJ dysfunction (see page 20). Many a patient withundiagnosed cluster headaches, whose pain centered aroundthe upper rear molars, has had teeth extracted unnecessarily.Fortunately, we now have effective treatments for clusterheadaches to reduce the frequency and severity of the attacks(see Chapter 11). If the diagnosis is made, effective treatmentusually follows.

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OTHER TYPES OF HEADACHE

Exer tional HeadacheAn exertional headache is brought on by physical effort of anytype, including bending, coughing, sneezing, straining, exercise,and even sex.This type of headache should always be broughtto a doctor’s attention because underlying abnormalities of thebrain, although not common, should be looked for carefully.

Jabs and Jolts (Ice Pick–Like Pains)Headache known officially as idiopathic (cause unknown) stab-bing headache is perceived as very sharp, extremely brief icepick–like pains or “jabs and jolts” at various locations in thehead. These headaches occur singly or in volleys over a fewminutes and return at least occasionally or up to several timesa day in about 40% of migraine patients.They can always be inthe same place, but most often they move around. They areusually benign, and no cause is found.A recent treatment hasbeen the use of off-the-shelf melatonin, 3 to 12 mg per day,usually given at bedtime. It is worth remembering, however,that the US Food and Drug Administration does not regulatenutritional supplements, so the ingredients and potency ofover-the-counter supplements may vary.

Sex HeadacheSex headache or coital headache is an intense headache thatoccurs primarily in men at the time of orgasm, although it canoccur in women. It is so severe that the first episode usuallycauses the patient to be taken to the emergency room.A seriesof tests should be performed to ensure that there is no under-lying brain problem. If no cause is found, the headaches oftenstop occurring after several months. Indomethacin, a non-steroidal anti-inflammatory medication, taken either beforehaving sex or on a daily basis, is frequently helpful in decreas-ing or stopping the pain (see above).

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Episodic and Chronic Paroxysmal HemicraniaEpisodic and chronic paroxysmal hemicrania is a rare type ofheadache disorder that resembles cluster headache. Unlikecluster headache, it occurs more commonly in women than inmen and is characterized by more than five brief attacks perday.The pain, which is always one sided, in and around an eye,lasts for only 5 to 10 minutes, is excruciatingly severe, and isassociated with at least one of the following autonomic signs:a red eye, tearing eye, drooping eyelid, small pupil, or stuffed orrunning nostril, all on the same side as the pain.

TREATMENT

The above headaches occur frequently in some patients. Exer-tional headaches, ice pick–like pains, and the paroxysmal hem-icranias may respond to the nonsteroidal anti-inflammatorymedication indomethacin (Indocin), 25 to 50 mg three timesper day. Indomethacin is available by prescription but, as withall medications, has some side effects that must be watched for.Ask your doctor if indomethacin would be a good medicationfor you to try.

“Ice Cream Headache”The official term for ice creamheadache is cold stimulus headachebecause it occurs after you eat ordrink something very cold, such as icecream. It lasts for fewer than 5 min-utes, is located between the eyes, andmay be prevented by eating ice creamslowly and in small amounts and byletting it melt in the mouth beforeswallowing (Figure 3-2). It may bemore prevalent in migraineurs.

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Figure 3-2: A boy aboutto experience an “icecream headache.”

Chronic Daily HeadacheStudies show that 4 to 5% of our population have chronic daily orfrequent headache.These patients have headaches that occur at least15 days per month and can be daily. Often patients say that theheadache waxes and wanes throughout the day,but that even whenit is not bothering them, it is present. It wears them down.Occa-sionally, the pain becomes sufficiently severe that it interferes withtheir ability to function.This type of headache clearly resemblesmigraine on some days, sometimes frequently. Some experts be-lieve that these patients have transformed migraine,which starts inthe teens with occasional, severe migraine attacks and transformsto daily waxing and waning pain (mild,moderate,or severe) by thetime they are in their thirties and forties.Eighty percent of peoplewith chronic daily headache seen in doctors’ offices take pain re-lievers or other acute care medications (such as triptans) on a dailybasis.This can result in rebound headache or transformed migrainewith medication overuse.The current thinking is that the overuseof these medications prevents the brain’s natural pain-fightingmechanisms from working.The result is more frequent and severeheadaches that do not respond to the usually effective medications(see Chapter 8).Intensive,carefully designed treatment can be help-ful to the majority of these patients.

Hemicrania ContinuaAnother form of daily headache is a strictly one-sided headachethat never switches sides but is present all of the time.This type ofheadache will get worse for hours to days and then return to amoderate level of pain. Patients with hemicrania continua willoften have symptoms of a red eye, tearing eye, runny nose, ornasal congestion.This type of headache also usually responds toindomethacin completely, like a key in a lock.

Post-Traumatic HeadachePost-traumatic headaches are caused by injury to the head orneck and may even develop after what seems to be only a minor

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injury. The headaches usually begin within 24 hours but, onoccasion, not for several days or weeks after the injury. Theseheadaches usually occur on both sides of the head; they are con-stant, are mild to moderate in intensity, and can continue formonths or years.The great majority of people who suffer a heador neck injury in an automobile accident or strike their heads ona low beam have a headache for 48 hours to a few weeks. Some-times the headaches become severe or even incapacitating, lastingfor months or years, and resemble migraine at times. Patientswith post-traumatic headache may be thought to be exaggerat-ing their pain or malingering, but in our experience, thesepatients have a debilitating disorder that may destroy the fabric oftheir lives and seriously impair their ability to function for years.

Some patients with post-traumatic headache also developpost–head trauma syndrome and experience impaired concen-tration, memory, and sleep, as well as irritability, decreasedenergy and interests, inability to perform sexually, personalitychanges, and decreased ability to handle even simple tasks.Although diagnostic tests such as scans of the brain or the cer-vical spine and electroencephalograms fail to reveal abnormal-ities, the injury may have caused microscopic bleeding ortearing and damage to nerve fibers in the brain, brainstem, andspine, as well as metabolic changes.The damage may disrupt thedelicate balance of the chemical messengers that control pain.Many patients develop post-traumatic headache as a result ofwhiplash (a neck injury) after a car accident in which theywere rear-ended. Sometimes they do not even strike their head.The degree of head trauma does not necessarily correlate withthe degree of pain intensity or disability. Preexisting migraineor tension-type headache may worsen after this kind of injury.

“Sinus Headache”Sinus problems rarely cause chronic headaches.The term sinusheadache was invented by advertisers to sell decongestants and

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over-the-counter antihista-mines. In fact, ear, nose, andthroat doctors do not recog-nize sinus headaches in theirlist of diagnoses. Rather,they note that headache cansometimes occur as a minorsymptom accompanyinginfections of the sinuses, thatis, acute sinusitis. Blockageof the sinus drainage systemmay cause infection, andthese infections are classifiedas acute or chronic sinusitis.Headache caused by acutesinusitis may be felt in thecheeks or below, above, orbehind the eyes or may bereferred to other areas, suchas the teeth or the top of the head (Figure 3-3).Acute sinusitisis generally associated with fever, red-hot skin over the sinus,and a yellow-green bad-tasting or -smelling discharge fromthe nostrils and back of the throat.

Any headache associated with fever or infection must betreated immediately. Chronic low-grade inflammation of anyof the sinuses in the head may rarely cause headache.The painpatterns are similar to those in acute sinusitis but are of lesserintensity and are not usually associated with fever. Dependingon the sinuses involved, pain may be increased by shaking thehead or by lying in certain positions that decrease the ability ofthe sinuses to drain. A severe sinus problem may trigger amigraine attack. However, most patients who think they havechronic sinus headache do not. A large study of over 3,000people with self-diagnosed or doctor-diagnosed headache hasbeen completed that found that 90% of these headaches were

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Figure 3-3: Diagram of sinuses inthe head and face.

migraine or probable migraine.Thus, disabling headaches thatlast for 1 to 3 days, occur several times per month, and areassociated with weather triggers, nasal stuffiness, clear drainage,tearing eyes, or postnasal drip are usually migraine.

Allergy HeadacheCommercials and advertisements to the contrary, mostheadaches are not brought on by allergies. Rarely, allergy topollen and grasses and hay fever can cause sinus pain andheadache if the sinuses fill up because of the allergic reaction.

Eye-Related HeadacheEye strain is not a common cause of chronic or recurrentheadache. Headaches that are due to eye strain are generallymild and are felt in the forehead or in the eyes themselves.Thepain is absent on awakening and worsens when the eyes areused for prolonged periods. Children with headaches are usu-ally checked early for eye problems, which often are notfound. Glaucoma (increased pressure within the eye) maycause a headache that mimics a bad migraine or tension-typeheadache, or it may cause severe pain in and around the eye orin the forehead. If you notice changes in your vision, especiallyif you see halos around lights, accompanied by pain and othersymptoms, consult an eye doctor at once.

Headache Caused by TMJ DysfunctionThe TMJ is located just in front of the ear, where the jawmeets the skull.TMJ problems may cause ear or jaw pain, ring-ing in the ears, clicking in the joint, or pain (headache) in thearea where the hinges of the jaw meet the upper face. Manypatients have been misdiagnosed as having TMJ problems andhave undergone major surgical reconstruction of the jointwithout experiencing any relief of their pain. Most “TMJheadaches” are actually migraine or tension-type headaches.Some patients do grind their teeth at night and have sore jawmuscles, and that can be a cause of early-morning headache.

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Trigeminal NeuralgiaTrigeminal neuralgia is a piercing sudden-onset severe painthat lasts for 1 second to 2 minutes and is confined to thecheek, jaw, or, rarely, the forehead on one side of the face.Thistype of pain is triggered by talking, chewing, exposure towind, or even touching the face. It can continue daily formany months and then often disappears for a while. It comesfrom a problem with the trigeminal nerve and is treated withmedication and, on rare occasions, surgery.

Spinal Tap HeadacheSpinal tap headache occurs 12 to 48 hours after a diagnosticspinal tap (lumbar puncture) in which fluid is removed from thespinal column. It is a diffuse, steady pain in the head and neckaccompanied by nausea. It gets worse on standing and disappearson lying down.The headache occurs because fluid leaks from thespinal column at the spot where the needle puncture was made.Scientific articles suggest that the smaller-size needles with a spe-cial point may lessen the chance of these headaches. Somepatients can develop a low-pressure headache spontaneously dur-ing a severe coughing spell or episode of trauma.The treatmentis to drink sufficient fluids and to lie absolutely flat for 2 days.This type of headache disappears slowly.An injection of caffeineor type of steroid tablet may be helpful. In severe cases, a minorprocedure called an epidural blood patch is performed to seal thehole and prevent further leakage of spinal fluid.This is successfulover 90% of the time if done properly.

CONCLUSION

The three primary headache disorders account for mostheadache problems. But there are other types of headache,some probably not yet discovered. After reading this chapter,you should have a good idea of what type of headache youhave. Many people have more than one type, which makes itdifficult for most doctors to determine the proper treatment.

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Our patients frequently ask us, “What causes my head-aches?” Another frequently asked question is, “If all my testsare normal, and nothing’s seriously wrong, why do I getheadaches?” Understandably, patients with unexplained symp-toms fear the worst, and when most causes of headache havebeen ruled out, they may fall back on media-driven explana-tions that attribute headache to sinus, allergy, and stress-relatedproblems. It is not surprising that when test results are normal,many patients fear that their headaches are not real but, rather,the result of a psychological process. This is not usually thecase. Unfortunately, there are no biologic markers or accuratetests to confirm the diagnosis of the most common headachedisorders. Diagnosis of headache is based on a detailed medicalhistory, neurologic and physical examinations, and appropriatetests. Most causes of headache probably do not show up onroutine tests because we do not yet have the specific means tomeasure biochemical and electrical changes in the brain, theblood vessels, and the muscles. Special testing is not alwaysnecessary; sometimes headache is diagnosable by an accuratehistory and neurologic examination.

CAUSES OF MIGRAINE

The tendency to develop migraine is inherited; up to 90% ofpeople with migraine have a close relative who gets them too.Your family history can give your doctor important informa-tion that may suggest migraine as a diagnosis. Some studiesshow that if one parent has migraine, each child has a 40%chance of developing it; if both parents have migraine, eachchild has a 75% chance. Four main theories about the cause ofmigraine have been proposed.The theories center on the fol-lowing: (1) the brain (the central theory); (2) the blood vessels

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CAUSES OF HEADACHE

CHAPTER 4

(the vascular theory); (3) inflammation (the neurogenicinflammation theory, which involves the trigeminovascularsystem) (Figure 4-1); and (4) a combination of these factors(the unifying theory), which pulls the three interrelated theo-ries together. At the beginning of a migraine attack, there islikely a “generator” that turns on subsequent events.

The Brain: Central TheoryDifferent experts in headache have different theories on thecause of migraine; these ideas are not mutually exclusive. Onewidely accepted belief is that the migraine brain is too easilyexcited.According to this theory of a “sensitive” or “hyperex-citable”brain, nerve cells in the brain fire too easily and therebystart the migraine attack.A variety of internal and external trig-ger factors cause the brain to wind up into a migraine; sometriggers are readily apparent (such as fatigue, lack of sleep, toomuch sleep, stress, the weather, and menses), whereas other fac-

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Figure 4-1: Anatomy of brain and scalp showing the trigeminovascularsystem.

tors are never found. But the critical understanding is that it isnot the triggers that cause the migraine but rather it is the irri-table nerve cells in the brain. Dr. K. M. A.Welch, president ofThe Rosalind Franklin University of Medicine and Science,and Dr. Nabih Ramadan, both neurologists and clinicalresearch scientists, observed that magnesium levels in the brainare low in migraine patients. One theory holds that low mag-nesium levels may be a cause of abnormal brain electrical activ-ity that starts in the back of the brain during the visual auraphase and spreads slowly forward.Thus, low magnesium levelsin the brain may be a cause of the abnormal brain-electricalactivity of migraine. Low magnesium increases the irritabilityof the nerves, producing electrical changes.

The Generator: BrainstemAnother area of the brain that may be hyperexcitable isthe lowest part, called the brainstem (see Figure 4-1). Nervecells in the brainstem contain a large amount of a chemicalcalled serotonin, which regulates pain. Dr. Neil Raskin, profes-sor of neurology at the University of California in San Fran-cisco, CA, believes that headache results from a disturbance ofserotonin activity in the midbrain, which is the upper partof the brainstem. This area of the brain may have a switchor generator that turns on at the beginning of a migraineattack and may cause the migraine to persist for days if notproperly treated.The fact that several medications effective inmigraine affect serotonin receptors suggests that serotonin mayplay a crucial role.

The Generator: Cor tex and Cor tical Spreading DepressionSome headache scientists believe that all migraine begins inthe cortex, the “thinking” part of the brain.The activation ofthis area in migraine is called “cortical spreading depression,” aterm that is not completely accurate because activation comesfirst, then depression! Cortical spreading depression (CSD) is

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definitely the cause of typical aura, which is described as areversible neurologic event lasting more than 5 minutes andless than an hour, and usually followed within an hour by themigraine headache. Aura, as described in Chapter 3, is oftenvisual, in the form of zigzags, flashing lights, or shimmeringblind spots, but occurs in only about one-fifth of migrainesufferers.Whether CSD happens in migraine without aura iscontroversial. CSD in the cortex may be a generator for allmigraine, but this is unresolved.

The Blood Vessels: Vascular TheoryIn the seventeenth century, Sir Thomas Willis proposed thatmigraine was caused by changes in blood vessel activity, a the-ory updated at the New York Hospital during the midtwenti-eth century by Drs. Harold Wolff and John Graham.The factthat ergotamine tartrate (contained in the medicine Cafergotused in those days) given intravenously noticeably decreasedthe painful throbbing and pulsations of swollen arteries in thescalp supported this theory. However, ergotamine and itsdescendants, the newer triptans, also work on serotonin recep-tors to turn off migraine, but this was not known at the time.It is not clear whether the blood vessel–constricting effects arenecessary for antimigraine drug action or whether the nerveeffects are sufficient. Because anti-inflammatories do not haveblood vessel effects, and because of recent studies on medica-tions that work in migraine via nerve effects without bloodvessel effects (classes such as “5-HT1F agonists” and “CGRPreceptor antagonists”), consensus is growing that blood vesselnarrowing is not necessary for turning off migraine.

Trigeminovascular System: Neurogenic Inflammation TheoryDr. Michael Moskowitz, professor of neurology at HarvardMedical School and Massachusetts General Hospital inBoston, MA, has shown that the trigeminovascular system of

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the brain is the key pathway of migraine pain. This systeminvolves 1 of the 12 cranial nerves—the trigeminal (or fifthcranial nerve)—and its connections between the arteries inthe covering of the brain (the meninges) and the nerve cells inthe brainstem. Chemicals released from the peripheral ends ofthe trigeminal nerve cause inflammation to occur aroundblood vessels. Many medicines effective in treating migraine—including the triptans and ergotamine (see Chapter 9)—act atthe interface of the trigeminal nerve endings and the vascularsystem in the meninges by reducing the release of these irri-tating chemicals and thereby decreasing the pain.

It may be useful to think of migraine as a process occurringin a “central generator” in the upper brainstem that is setincorrectly so that it fires too easily.When this switch turns on,nerves fire and activate the trigeminovascular system, causinginflammation and blood vessel dilation to occur in themeninges. From there, the pain signal goes back into thebrainstem, where it is integrated and where nausea and othermigraine symptoms are generated.

One of the chemicals released in the meninges that causesboth inflammation and blood vessel dilation is called calci-tonin gene-related peptide, or CGRP. This substance is alsocontained in areas of the brain associated with the trigeminalnerve and pain. Further, CGRP is also released by peripheralnerves of skin or muscle, and may contribute to inflammationin the face, scalp, and neck. It is present in all of the areasinvolved in the brain, head, and neck that could be involved inthe causes of migraine.

Therefore, migraine occurs as a three-step process:

1. Activation of the migraine central generator in the brainstem

2. Activation of the peripheral pain mechanism,which is causedby inflammation, and blood vessel dilation in the meninges

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3. Reentry of the pain signal into the brain for integrationand initiation of nausea and other migraine symptoms,which last until the central generator switch turns off

Recent research at the Beth Israel Hospital and HarvardMedical School in Boston by Dr. Rami Burstein from Israelshows the windup or buildup in the brain (called central sensi-tization) and suggests that the sooner a migraine attack isstopped by medication, the less severe that attack will be. Hehas also pointed out that many patients whose migraineattacks are not stopped early develop sensitivity of their skin tonormal touch, called cutaneous allodynia. They describe beingunable to comb and brush their hair, to wear a hat, glasses, ear-rings, or tight collars, or to have anyone touch their skin farinto a migraine attack because it hurts them. This correlateswith the abnormality in the brain called central sensitization andalso often correlates with the triptans not working as well tostop the migraine attack. As you can see, much progress hasbeen made that is beginning to shed more light on our under-standing of migraine as a neurologic disorder.

MIGRAINE TRIGGERS

As noted above, triggers do not cause migraine but, rather,turn on the central switch to initiate the process. Manymigraine patients are unusually sensitive to internal (withinthe body) and external (outside the body) environmentalchanges (Table 4-1).A variety of factors can trigger an explo-sive migraine attack (Figure 4-2). The menstrual cycle isclearly a major trigger in the great majority of women; a sec-ond trigger is food. Although alcoholic beverages are com-mon triggers, red wine, beer, and champagne are the drinksmost frequently mentioned by patients. The dark-coloredalcohols (scotch, bourbon, dark rum, and red wine) appearmore likely to trigger migraine attacks than the light-colored

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ones (gin, vodka, white rum, and white wine). Many foods(Table 4-2), particularly those that contain tyramine, triggermigraine, but only in some people.

Monosodium glutamate (MSG), an ingredient added to awide variety of preserved and frozen foods, can trigger mi-graine. Read food labels carefully. Look not only for MSG butfor the words hydrolyzed fat or hydrolyzed protein. Both Nu-trasweet, a food ingredient, and Equal, a sugar substitute, con-

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Table 4-1: Triggers of Migraine

IInntteerrnnaallChronic fatigue, too little sleep, too much sleepChange in sleep-wake cycle from travel or shift workEmotional stress, letdown after the stress is overHormonal fluctuations (menstrual cycle)

EExxtteerrnnaallWeather and seasonal changeTravel through time zonesAltitudeSkipping or delaying mealsSensory stimuliFlickering or bright lights, sunlightOdors, including perfume, chemicals, cigarette smokeHeat, loud noises

MMeeddiiccaattiioonnssNitroglycerinTetracycline (an antibiotic)High doses of vitamin ASome antidepressant medications (selective serotonin reuptake inhibitors

or SSRIs)Some blood pressure medicationsMonosodium glutamate (MSG) (a food ingredient)*Nutrasweet (a food ingredient),** Equal (a sugar substitute),**

possibly Splenda (an artificial sweetener) #

*MSG is added to a wide variety of preserved and frozen foods and can trigger migraine.FFoooodd llaabbeellss sshhoouulldd aallwwaayyss bbee ccaarreeffuullllyy rreeaadd.. Look not only for MSG but also for thewords hydrolyzed fat or hydrolyzed protein.

**Both contain aspartame and have been associated with headache in susceptible individuals,especially if taken in large amounts (several diet sodas or other aspartame-containing foodsper day).

#Contains sucralose, reported by some headache specialists to trigger migraine.

tain aspartame, and bothhave been associated withheadache in susceptible indi-viduals, especially if they aretaken in large amounts (sev-eral diet sodas or other as-partame-containing foodsper day).

Caffeine is a double-edged sword. Because caf-feine may help constrict thedilated blood vessels duringa migraine attack, it is usedin combination medicinesto increase relief fromheadache (eg, ExcedrinMigraine is a combinationof acetylsalicylic acid [ASA],acetaminophen, and caf-feine; Fiorinal contains caf-feine; Cafergot containscaffeine). However, habitualconsumption of too muchcaffeine can make headaches

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Table 4-2: Dietary Triggers

Chocolate, onions, Nutrasweet, Equal (aspartame), Splenda (sucralose)Nuts, pizza, canned figs, peanut butter, avocado, aged cheeseBananas, processed meats, caffeine (see also Table 4-3)Alcoholic beverages, eg, red wineHot dogs, pepperoni, sausages, bacon, ham, bologna, salamiPickled or fermented foodsYogurtSour cream

Figure 4-2: Triggers that set off theexplosion of migraine.

worse. How much caffeine is too much? Some patients aresensitive to the small amount of caffeine (approximately 100mg) in one small (5 oz) cup of brewed coffee. Many patientswho complain of headaches on Saturday or Sunday morningstake in less caffeine on weekends than during the week orsleep later and therefore drink their coffee later in the morn-ing. Headaches that occur under these circumstances could bedue to caffeine withdrawal and are more likely to occur inpeople who are accustomed to drinking more than 300 mg ofcaffeine per day (about three cups of coffee). At 500 mg perday or above, caffeinism, with symptoms that include disturbedsleep, anxiety, nervousness, rapid or irregular heartbeat, andirritability, may occur. Table 4-3 lists the caffeine content ofvarious products and foods.

StressAlthough stress is high on the list of migraine triggers, it doesnot usually cause migraine headaches in those who are notbiologically predisposed to migraine.When stress does cause aheadache, it is usually a tension-type headache and shoulddecrease as soon as the stress lessens. Migraine is likely to occurduring letdown periods, such as after the stress has come andgone, or during a period of unwinding or relaxing.This mayexplain why many patients have migraine attacks on weekendsor on vacations.

MensesThe most frequent trigger of migraine in women, after stress, ismenstruation. Presumably, the drop in estrogen just before flowis the trigger.The predictability of this trigger allows for certainspecial treatments for menstrual migraine (see Chapter 16).

CAUSES OF TENSION-TYPE HEADACHE

Early theories of causes of tension-type headache attributedthe pain to contraction of muscles around the head and neck,

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which explains why this type of headache was originallytermed muscle contraction headache. It is true that tension-typeheadache may occur in people who—for one reason oranother—unconsciously tighten up the muscles around thehead, neck, and shoulders. All of the following may also betriggers of tension-type headache: poor posture, tense jaw,temporomandibular joint problems, arthritis, disk disease inthe neck, and occupational factors, such as sitting for longperiods at computer terminals, typing, or cradling the tele-

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Table 4-3: Caffeine Content of Common Foods and Drugs (in mg)

CChhooccoollaattee,, CCooffffeeee,, aanndd TTeeaaChocolate candy bar 25Cocoa beverage (175 mL mixture) 10Coffee

Decaffeinated (150 mL) 2Drip (150 mL) 146 (This would be one to two 8 oz cups)Instant, regular (150 mL) 53 (This would be about one 8 oz cup)Percolated (150 mL) 110 (This is about one 8 oz cup)Starbucks regular grande 320

Tea 3-Minute brew (150 mL) 22–46 (This is about one 8 oz cup)

OOffff--tthhee--SShheellff DDrruuggssAnacin 32Extra-Strength Excedrin 65Excedrin Migraine 65 (2 tablets contain 130 mg)No-Doz tablets 200Vanquish 33Vivarin tablets 200

PPrreessccrriippttiioonn DDrruuggssDarvon Compound 65, 32Esgic 40Fioricet 40Fiorinal 40

SSoofftt DDrriinnkkss ((335500 mmLL)) 7-Up/Diet 7-Up 0Coca-Cola 34 (One can)Diet Coke 45 (One can)Dr. Pepper 41(One can)Mountain Dew 55 (One can)

phone between the ear and the shoulder. It is easy to under-stand how tight muscles could be related to tension-typeheadache, but factors within the brain may be involved as well;tension-type headache may have nothing to do with musclesor tension in some patients.

POSSIBLE CONNECTIONS BETWEEN TENSION-TYPEHEADACHE AND MIGRAINE

Because some of the symptoms of tension-type headacheand migraine overlap, and because many people suffer fromboth types of headache, several headache specialists believethat these two conditions are related. Many patients maydevelop an acute tension-type headache that, over a periodof hours, evolves into a clear-cut migraine. It is not surpris-ing that one group of headache specialists believes thatheadaches represent a continuum that includes tension-typeheadache and migraine, which share similar underlyingmechanisms. Another group considers the two headachetypes to be completely distinct disorders. A third and newertheory is that tension-type headache that occurs in migrainesufferers is really just low-level migraine, whereas tension-type headache in people who do not get migraine is a dis-tinct and separate type of headache. Dr. Roger Cady, familypractitioner and director of the Primary Care Network inSpringfield, MO, and Prof. Richard Lipton, professor of neu-rology and public health at the Albert Einstein College ofMedicine in the Bronx, NY, have provided recent evidencethat supports this third hypothesis. Depression and anxietyare often associated with chronic daily headache, tension-type headache, and migraine and should be addressed as partof a patient’s entire headache picture. Some patients withdepression and anxiety need behavioral treatment from apsychologist, and some may need medication.

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CAUSES OF CLUSTER HEADACHE

The causes of cluster headache are complex.According to Dr.Lee Kudrow, a well-known retired internist and headache spe-cialist in Beverly Hills, CA, a tiny nerve bundle that regulatesbody rhythms deep within the hypothalamus of the brain isresponsible for bringing on cluster headaches with clocklikeregularity each day. It may also bring them back the same weekthe following year. Further evidence for involvement of thisdeep area of the brain was provided by Dr. Peter Goadsby, pro-fessor of neurology now at the Umniversity of California, SanFrancisco and his colleagues by means of specialized brainscanning (positron emission tomography scanning) when theyfound the “central generator” for cluster headache to be in thehypothalamus. Lithium carbonate has provided effective treat-ment for some patients, perhaps because it is believed to regu-late the hypothalamus, which houses the body’s biologic clock.Cluster headache also involves certain blood vessels and causeshyperactivity of the parasympathetic nerves, which results inthe red and tearing eye and the stuffed or running nostril thatare associated with the pain. Exciting new experimental treat-ment of cluster headache has been investigated by two neurol-ogist-headache specialists in Milan, Italy. Drs. Gennaro Bussoneand Massimo Leone suggested that an electrical stimulator beplaced in the brain deep into the hypothalamus in their 14toughest patients with cluster headache who did not respondto any therapy.They all had a cessation of pain some time afterthe electrical simulation began. Further research may be bene-ficial for cluster sufferers. Further clarification of the biologicmechanisms will help doctors understand more aboutheadache and will yield more specific treatments. The nextdecade should bring answers as to how migraine is inheritedand, hopefully, how to prevent it from starting.

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More than 95% of headaches are primary headaches thatare not caused by serious underlying medical conditions.Youshould, however, be aware of the “red flags” or danger signalslisted below because these are signs that you should seek med-ical attention.

Consult a doctor if you experience any of the following:

• You rarely get headaches and suddenly develop a severeone.

• You often get headaches and develop a new type or onethat comes on suddenly and remains severe.

• You develop the worst headache you have ever had.• You are over 40 years old and start to develop headache for

the first time.• You develop a headache that gradually worsens over a

period of days or weeks.• You get headaches when you exercise, cough, sneeze, strain

while having a bowel movement or during other strenuousactivities, have sex, or bend over. (They could be exertionalmigraine or benign exertional headaches, but you may havesomething more serious.)

• You get a “bug” or virus, and you develop a severeheadache accompanied by nausea and vomiting and a neckso stiff that you cannot put your chin on your chest with-out pain.You must seek medical attention right away torule out meningitis or hemorrhage.

• You get a headache accompanied by any of the followingneurologic symptoms: trouble with coordination, doublevision, weakness or numbness in any extremity or on oneside of the body, drowsiness, inability to stay awake, confu-sion, impaired speech, or a change in personality.

DANGER SIGNALS

CHAPTER 5

• You have a serious underlying disease already, includingcancer, auto-immune disease such as lupus, or a chronicinfection such as human immunodeficiency virus (HIV).With significant underlying illness, headache can be asymptom of a life-threatening problem.

• You have a change in the pattern of your headaches, interms of frequency, severity, or duration.This includes thenew onset of daily headache.

DANGER SIGNALS

In general, these should be medically evaluated as soon as possible:

• A new-onset headache in someone who does not usuallyget headaches

• A headache that is much more severe than usual • A significant change in a typical headache • A headache that escalates in severity more rapidly than

usual or steadily over many days.

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When you visit your own physician or a neurologist orheadache specialist, you should be questioned carefully aboutyour headaches. The doctor should ask about each type ofheadache you have and request details, such as the following:When did it start? How frequently do you get this type ofheadache? How long does it last? How does it impact on yourlife? Where is the pain located? How severe is it? Are thereother symptoms associated with it, such as nausea, vomiting,and sensitivity to light and sound? What brings it on (triggersit)? What makes it better? What is your behavior like during theheadache? Your doctor will then do a physical and neurologicexamination and evaluate your mental alertness; cranial nervefunction, including vision and hearing, and strength and sensa-tion of the face; strength, coordination, and walking; reflexes;and ability to perceive different sensations. In addition, yourblood pressure, pulse, neck motion, and the state of the arteriesin your head and neck will be evaluated (Figure 6-1).

Although the histories of migraine sufferers are dramatic,most people usually turn out to have basically normal neurologicexaminations. In fact, people with migraine and tension-typeheadache should have normal examinations; if the examination isabnormal, the doctor will become concerned that anotherprocess may be causing the headaches. Even if your examinationis normal, your doctor may order blood tests to check for infec-tion and inflammation,metabolic problems, liver or thyroid dys-function, and perhaps Lyme disease, anemia, and other conditionsthat might contribute to your headaches. Do not be surprised ifyour doctor sends you for a computed tomography (CT) scan,magnetic resonance imaging (MRI) of your head, or even mag-netic resonance angiography (MRA) because these are the bestways to rule out serious structural problems in the brain. CT,

THE DOCTOR’S ROLE

CHAPTER 6

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MRI, and MRA are painless. CT involves the use of x-rays; aniodine-containing dye may be injected into an arm vein toincrease the contrast of the images. Be sure to tell your doctor ifyou are allergic to iodine. MRIs and MRAs do not use x-rays;rather, they are done in a strong magnetic field.Another type ofdye may be injected into an arm vein. Most MRI machinesresemble a small tunnel, open at both ends (Figure 6-2). MRIsusually cost more than do CT scans, but they provide moredetailed information about more areas of the brain. Pregnantwomen should not undergo either scan, but an MRI is prefer-able to a CT scan when imaging is necessary.Be sure to tell yourdoctor if you are going for an MRI and you had any metal hard-ware placed in your body during previous surgery. For patientswho are claustrophobic,open MRI scanners are less threatening.Health maintenance organizations and managed care companiessometimes try not to cover some of these expensive tests, but ifthey are essential, your doctor should be able to convince thecompany of their importance.

Figure 6-1: The neurologic examination should include listening forabnormal sounds (bruits) in the neck.

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A spinal tap (lumbar puncture) may be indicated if yourheadaches are severe and are associated with a stiff neck, fever,vomiting, and signs of increased or decreased pressure in the brain.The most important abnormal findings from a spinal tap are evi-dence of bleeding, infection, or increased or decreased pressure.Patients are often told to lie flat for several hours after a spinal tapto avoid an increase in headache pain.An electroencephalogram,during which many wires are attached to the scalp, can be usefulwhen evaluating headache patients whose histories include faint-ing, loss of consciousness, seizures, head trauma, or dizziness.

The most important part of your evaluation is the historyyour doctor obtains from you. It alone can point to an accu-rate tentative diagnosis that can be confirmed by appropriateexamination and testing. So prepare your history in advanceby writing down all of your symptoms, the tests you have had,and the medications you have tried. Bring in calendars youhave kept, lists of medications, and reports of tests. Be sure totell your doctor the impact that your headaches have on yourlife. If there are times that, because of your headaches, you areunable to work, go to school, do household chores, or partici-pate in family and social activities—or can only do these activ-ities at a decreased level of efficacy—discuss these issues withyour doctor early in your visit. Most of the time, if the historyand examination are complete and detailed at the first visit, atreatment plan can be begun immediately.

Figure 6-2:Patient await-ing CT scan.

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Until recently, the biologic basis of head pain was poorlyunderstood, and many headache sufferers were thought tohave psychological problems as the basis of their headaches.Some still view psychiatric disorders as the primary causes ofchronic pain and headache.This may be why headache is stillnot always considered a legitimate complaint and why somepatients with headache are not taken seriously.

We do not have all of the answers, but we do know thatheadache has a firm basis in the neurobiology of the brain.Although psychological factors such as personality style,depression, anxiety, and stress can influence headache, they arerarely the cause of it. All medical disorders, however, areaffected by psychological factors.We cannot completely sepa-rate our minds from our bodies.

Psychological factors fall into three categories: (1) thosethat do cause headache (they are the least common cause), (2)those that contribute to it, and (3) those that coexist with it.

FACTORS THAT CAUSE HEADACHE

Psychogenic FactorsThe term psychogenic suggests that the pain is either not real orthat it is somehow different from real pain.The patient is notmaking it up, but there is no obvious physical cause of the pain.

MalingeringMalingering is the intentional production of false symptoms—inother words, conscious lying or faking. It may occur in drug orsubstance abusers or when people are trying to avoid situationsthey do not like, such as school, work, jail, or combat duty.However, malingerers are rare, despite the misconception thatpeople often fake head pain after experiencing trauma. Patients

PSYCHOLOGICAL FACTORS

CHAPTER 7

who have headache after car accidents usually have physiologiccauses of the headache, not psychological ones.

Migraine PersonalityThe term migraine personality has generated much confusion.The origin of the term is attributed to Dr. Harold Wolff, aneurologist working at The New York Hospital, NY, in theearly 1960s, who noticed that a large percentage of hismigraine patients seemed to have strikingly similar personalitycharacteristics. However, according to Dr. Randall Weeks,director of The New England Institute for Behavioral Medi-cine in Stamford, CT, and a long-time colleague of ours, weknow that the personalities of migraine sufferers differ very lit-tle from those of the rest of the population.There are peoplewithout headache who appear to have the migraine personal-ity, and there are those with migraine who do not have it.

FACTORS THAT CONTRIBUTE TO HEADACHE

We believe that the common primary headache disorders areneurobiologic in origin and are genetically determined. Once apatient has the biologic vulnerability to develop headache,behav-ioral changes and stress may trigger one or make one worse.

StressThe body is subject to stress when called on to react tochanges in the environment.When stress is overwhelming orconstant, physical or emotional symptoms may occur.Areas ofstress include difficulties at the workplace, marital problems,illness, financial problems, difficulty at school, and caring for asick relative. Stress is not always negative, however. Positiveevents such as purchasing a house, getting married, having achild, moving, or changing jobs can be stressful too.

Migraine patients often do well when they are going at“full speed.” They may, however, develop migraine after thestress is resolved and they begin to relax; this explains why

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some patients experience attacks on weekends, during vaca-tions, and when projects are completed. Patients suffering fromcluster headaches tend to get their headaches after a nap orduring the letdown time after work, when they are relaxingafter a hard day.This is not a psychological phenomenon butone that can be explained by changes in brain chemistry.

PSYCHIATRIC DISORDERS THAT COEXIST WITH HEADACHE

Migraine and related disorders do not protect an individualfrom developing psychiatric problems or other physical prob-lems.The prevalence of depression, anxiety disorders such aspanic attacks, phobias, and sleep disorders is higher in patientswith migraine and chronic daily headache.Although the exactrelationship between head pain, anxiety, sleep disorders, anddepression is not completely understood, we do know thatserotonin, a chemical that occurs naturally in the brain, plays arole.The “serotonin connection” suggests that all of these dis-orders share an underlying biologic cause.There is some evi-dence that migraine, depression, and anxiety are sometimesinherited together.

Studies by Dr. Naomi Breslau at the Henry Ford Hospitalin Detroit, MI, show that migraineurs experience moredepression and that depressed patients have more migraines.Table 7-1 lists some common symptoms of depression andanxiety disorders. If you experience symptoms of anxiety ordepression, you may want to consider the possibility that youhave a treatable psychological problem. Head pain is thedepressed patient’s most frequent physical complaint. Patientswith chronic daily headache may also have depressive symp-toms that include difficulty sleeping, decreased interest ineverything they formerly enjoyed, decreased energy, anddecreased concentration.

If depression or anxiety coexists with your headache disor-der, it is difficult to treat one without addressing the other. Do

not be upset if your doctor suggests that you may be anxiousor depressed. He or she is trying to manage all of the factorsthat may contribute to your headache.You may be surprised tolearn that headache specialists frequently prescribe antidepres-sant medications, even if the patient is not depressed. Thesemedications raise your serotonin levels and can work againstheadache, depression, anxiety, and sleep problems.

CONCLUSION

Psychological factors may contribute to your headaches, butthey are rarely the cause.A variety of psychological tests may

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Table 7-1: Common Symptoms of Depression and Anxiety

DepressionDepressed moodDecreased ability to experience pleasure and decreased interestsSignificant changes in weightPersistent difficulty in falling asleep or staying asleepSleeping too muchOthers have observed that you are markedly slowed down or agitatedDecreased energy or increased fatigueFeelings of worthlessness, guilt, decreased concentration, and inability to make

even simple decisionsRecurrent thoughts of death

AnxietyShortness of breath or a feeling of smotheringDizziness or feelings of unsteadinessPalpitations or rapid heartbeatTrembling or shakingSweatingChoking or trouble swallowingNausea or abdominal distressA feeling that you are not real or that your environment is somehow not real

or has changedNumbness or tingling sensationsChills or flushingChest painFear of dyingFear of going crazy or doing something that you cannot control

help to identify depression and anxiety. Other disorders, suchas alcoholism and other forms of drug or substance abuse, mustbe identified as well. Although many headache patients mayoveruse medication, they are not often substance abusers;rather, they use medications in an effort to remain functionaland to decrease their pain.The end result is not usually good,however. Overuse of pain medication, caffeine, and other acutecare headache medications, such as ergots and triptans, canlead to analgesic rebound headache, a condition in which theoverused medications result in daily or near-daily headache.More information about analgesic rebound headache is pre-sented in Chapter 8.

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Headaches can be made more severe, more constant, andmore difficult to treat by overuse of off-the-shelf and prescrip-tion pain relievers such as ASA and acetaminophen, barbitu-rates, opiates, caffeine, ergotamine tartrate, and even thetriptans. Overuse often results in analgesic rebound headache.In addition, some medications prescribed for medical condi-tions other than headache may worsen or produce headache. Ifyou have headache and take a lot of medication, ask your doc-tor if any of them could be contributing to your headacheproblem.We have patients who were taking a medication forother medical conditions, such as heartburn and allergies, whodeveloped severe, difficult-to-treat headaches and who gotbetter only when the offending medications were stopped.

MEDICATION-OVERUSE HEADACHE (ANALGESIC REBOUNDHEADACHE)

Increasing your consumption of pain medication not only usu-ally fails to relieve headache, it may perpetuate and intensify it.This is known as medication-overuse headache, analgesic reboundheadache, or transformed migraine with medication overuse becausethe headaches “transform” from discrete episodes into a daily ornear-daily pattern. Most headache specialists agree that takingeither off-the-shelf or prescription pain medications more than3 days per week greatly increases the risk of developingrebound headache. Many patients who develop reboundheadache take more than one kind of pain reliever. Headachemedicines are often a combination of products (see Chapter 9)that include a variety of pain relievers, caffeine, and other sub-stances that affect blood vessels.Almost every medication takenacutely for headache used more than 3 days per week can causerebound. Even ASA and acetaminophen, and possibly the non-

MEDICATION-OVERUSE HEADACHE

CHAPTER 8

steroidal anti-inflammatory medications—alone or in combi-nation, with or without caffeine—cause rebound.

Two of the more common ingredients, in addition to caf-feine, that are included in acute care medications and thatcause rebound headache are butalbital, which is in Fiorinal,Fioricet, Phrenilin, and Esgic, and codeine, which is in Fiorinalwith codeine, Fioricet with codeine,Tylenol with codeine, andsimilar preparations sold under various brand and genericnames. Other sedatives and tranquilizers may also causerebound headache. Additionally, overuse of these medicationstends to reduce the usual effectiveness of daily preventive med-ications, “designer” migraine-specific acute care medicationssuch as triptans, relaxation techniques, and biofeedback train-ing. Daily caffeine intake from beverages and mixed analgesicsmay also contribute to the headache problem (see page 46).

So how does overuse of pain medications come about?Let’s say you often wake up in the morning with a mildheadache that you are afraid will get worse.To be on the “safeside,” you take a small dose of an off-the-shelf pain relieverevery morning. Before long, you are taking two pills every 4hours—or 6 to 12 tablets a day.

Over time, your headaches seem to get worse; this leadsyou to increase the number of pills you take. Before you knowit, you are taking large amounts of medication and, instead offeeling better, you feel much worse. Not only do you havemore headache, but you develop side effects from the medica-tion such as nausea or stomach pain. Rebound can also resultfrom use of an ineffective prescription medication for disablingmigraine. If you have disabling migraine, it is better to treatyour attacks with migraine-specific medication such as triptansright from the start of your therapy. If your physician gives youa low-level nonspecific medication and instructs you to take itwhen you get a migraine, the low-level medication is unlikelyto make you pain free or even better. If you are not pain free

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with the nonspecific medication, your migraine is likely torecur; this leads to re-treatment with the low-level medication.

Soon a cycle of treatment, medication wear-off, with-drawal, headache, and re-treatment sets in.This is the basis ofanalgesic rebound. Rebound headaches often occur in theearly morning after the medication has worn off through thenight. Patients may become anxious and depressed, may havedifficulty falling asleep, or, even more commonly, may awakenbetween 2:00 and 4:00 am and be unable to get back to sleep.They may also be irritable, have trouble concentrating, andexperience other neurologic and psychological symptoms.

Patients with analgesic rebound who have tried to stopoverusing pain relievers know that their headaches usuallyworsen before they get better.Their headaches may intensifywithin 4 to 6 hours after stopping the medication, becomingmost intense within 1 to 2 days.This withdrawal period maylast for 2 to 3 weeks.Withdrawal symptoms can sometimes beeased by the use of steroids, triptans, or nonsteroidal anti-inflammatory medications as a bridge to get through theuncomfortable period.

After gradually stopping their use of analgesics, mostpatients notice an improvement in their headache symptomsand in their general sense of well-being within 2 to 3 weeksand even more so within 2 to 3 months.They note that theirheadaches are less frequent and less severe. They feel better,sleep better, are less depressed, and worry less about gettingheadaches. Once overuse of pain relievers is under control,patients find that they respond to daily preventive medications,such as b-blockers, calcium channel blockers, antidepressants,and antiseizure medications, as well as to migraine-specificmedications such as triptans. Response to nondrug therapysuch as biofeedback training, vitamin B2 (riboflavin), and mag-nesium also improves. None of these treatments are effectiveduring analgesic rebound headache.

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HOW TO RECOGNIZE MEDICATION-OVERUSE HEADACHE

A typical rebound headache lasts between 4 and 24 hours.Thepain is mild to moderate, dull, nonthrobbing, and steady. It canoccur in any part of or all over the head and is usually felt onboth sides of the head rather than on one side. Frequently,rebound headaches occur with a great deal of neck pain ordiscomfort. In most cases, patients do not experience frequentmigraine-type symptoms, such as throbbing, nausea, increasedsensitivity to light and sound, or pain worsening with mildexertion. Sometimes, however, rebound headache does inten-sify into a severe migraine episode.The bottom line is if youhave headaches on average 4 days per week or more, and youtake acute care medications 4 days per week or more, you area prime candidate for developing rebound headache.

ERGOTAMINE MEDICATION-OVERUSE HEADACHE

Although ergotamine tartrate is effective in relieving acutemigraine, its overuse results in ergotamine rebound syndrome.Because it relieves migraine headache quickly when it works,patients with rebound are often tempted to use ergotamine foreach headache, even mild ones, and they soon find that theirergotamine-responsive headaches occur more frequently.Ergotamine rebound can occur with use as infrequent as 2days per week.Therefore, we limit our patients to 1 to 2 daysper week of using Cafergot-type medications.

CAFFEINE REBOUND HEADACHE

Many headache preparations contain caffeine, a stimulant andblood vessel constrictor that, when combined with analgesics,boosts headache relief. But caffeine can produce headacheboth when overused on a regular basis and when it is stoppedabruptly (see Chapter 4).

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At The New England Center for Headache in Stamford,CT, patients are questioned carefully about their caffeineintake. If it is high—over 100 to 300 mg per day, equivalent toabout one to three cups of coffee—we ask them to reducetheir coffee consumption slowly by one cup per week over aperiod of 2 to 3 weeks to avoid worsening of their headaches.Remember that a mug (depending on its size) can be equal totwo to three cups! Patients who abstain from caffeine for amonth or two can resume drinking one cup of regular coffeeper day and as much decaffeinated coffee as they like withoutbad results.Although patients often do not believe it, caffeine isoften part of their headache problem.

TREATMENT OF MEDICATION-OVERUSE HEADACHES

Treatment of rebound syndromes begins with a careful assess-ment of exactly what the patient is doing and a prescriptionfor appropriate medication and a behavioral wellness program.Patients should be given a detailed explanation of the syn-drome, help in withdrawing from the overused medications,and tips on avoiding the syndrome in the future. Biofeedbacktraining and relaxation techniques can be helpful, particularlywhen incorporated in a comprehensive behavioral program.

The key to treatment is to discontinue the overused med-ications and to break the cycle of daily headache. Off-the-shelf medication can be withdrawn gradually over a few days,but prescription medications should be discontinued moreslowly. Medications such as narcotics (opiates), butalbital-con-taining medications (such as Fiorinal), and caffeine-containingmedications should be reduced over a period of several weeks.Patients using large amounts of barbiturates, narcotics, or ergo-tamine for a significant period of time may require hospital-ization to enable them to receive effective doses of medicationto prevent severe worsening of headache and other symptomsas they withdraw from the offending medication. Outpatients

should have frequent office visits until withdrawal has beencompleted and improvement begins. They may need to taketime off from work or have help around the house until theyimprove.

The most effective in-hospital treatment is the administra-tion of intravenous dihydroergotamine (D.H.E. 45), to whichintravenous steroids, antinausea medications, and valproatesodium (Depacon) may be added. Several other intravenousmedications can also be used.After detoxification is complete,appropriate combinations of preventive medication can beprescribed. Then triptans are usually resumed in appropriateamounts for severe headaches. Detoxification does not meanthat one cannot use medications for occasional bad migraineattacks.The triptans can be used up to 2 to 3 days per week formigraine without causing rebound.

The follow-up behavioral wellness program should includevery detailed instructions on which medications to use andhow to take them to stay out of trouble with rebound, self-help techniques, dietary instruction, an exercise and fitnessprogram, and appropriate counseling.

NONHEADACHE DRUGS THAT MAY CAUSE HEADACHE

Some nonheadache medications used for other conditions cancause headache. Indomethacin (Indocin), a potent nonsteroidalanti-inflammatory medication, is very effective in someheadache syndromes. Some patients who take it for non-headache reasons may develop excruciating headaches, whichoften send them to an emergency room for evaluation. Once aserious problem has been ruled out and indomethacin hasbeen discontinued, the headache promptly resolves.

Nifedipine (Procardia), an effective calcium channelblocker used to treat high blood pressure by dilating bloodvessels, may induce a severe throbbing headache, even in non-headache patients. A similar headache may occur in patients

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who take nitroglycerin for chest pain. Some bloodpressure–lowering medications contain nitrates, which dilateblood vessels and cause headache. Sildenafil citrate (Viagra),vardenafil (Levitra), and tadalafil (Cialis), used by men forimpotence, dilate the blood vessels of the penis and can causedilation of head arteries and, consequently, headache.VitaminA and tetracycline in large doses can sometimes cause head-ache. Women who take estrogen cyclically notice headachewhen they stop their estrogen. Some women have an increasein headache when they start to take the birth control pill.Some of the new medications that stop heartburn and ulcers,the proton pump inhibitors, can induce headache. Finally,some of the newer selective serotonin reuptake inhibitor anti-depressants, such as Paxil (paroxetine hydrochloride), Prozac(fluoxetine hydrochloride), and Zoloft (sertraline hydrochlo-ride), can occasionally increase migraine.

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A t The New England Center for Headache, in Stamford,CT, patients are treated with both pharmacologic and non-pharmacologic methods (as described in Chapter 12). Ourphilosophy is to use as few medications as possible for theshortest feasible period of time. Overuse of medicationdesigned to treat acute headache can lead to rebound syn-dromes and dependency. Our major concern is with the num-ber of days per week that patients take the acute caremedication rather than the amount taken on any given day.Welimit use of acute care medication to a maximum of 2 to 3days per week because even small amounts taken daily mayinduce analgesic rebound headache. Sometimes it is beneficialto take two different types of medication for 2 or 3 days eachrather than 6 days a week of just one type.

Each patient’s medication program is based on that indi-vidual’s needs. All patients, however, are asked to accuratelyrecord on a headache calendar how much medication theyuse on a daily basis (see Chapter 12).

Headache medication falls into the following threecategories:

1. Symptomatic treatment. Medications in this category aredirected at symptoms such as pain, nausea, or vomiting;they may also help patients to relax and possibly sleep.

2. Specific (abortive) treatment. Medications in this categoryinterfere with the process that causes the headache, therebystopping pain and its associated symptoms, such as nausea,vomiting, and sensitivity to light and sound.

3. Preventive (prophylactic) treatment. Medications in thiscategory are taken daily to reduce or prevent frequentlyoccurring headache. They may also be prescribed forpatients who experience three or more migraine attacks

ACUTE TREATMENT OF ATTACKS WITH MEDICATION

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per month associated with considerable disability or thosewho have not experienced adequate relief from specificmedications, such as triptans.

Additionally, they are used when specific medications haveto be avoided, as when patients have heart disease or highblood pressure.The beneficial effects of these medications areusually not evident for 3 to 6 weeks and only at proper doses.Patients should not discontinue such medications withoutmedical advice because stopping them abruptly could result inserious side effects or an increase in headache.

Warning: All medications have side effects. Patientsshould understand the desired effects of medications, howthey work, and the side effects that may occur.Whenever weprescribe medication, we give our patients a list of side effectsso that they can watch out for them.To avoid side effects, westart medications at low dosages and build up slowly to theoptimal dosage.

DECIDING ON TREATMENT: STRATIFICATION OF CARE

Many health care providers believe that it is always best tostart with gentle inexpensive symptomatic medication forheadaches and to prescribe a more specific medication onlywhen the lower-level treatment has failed.This is referred toas step care because the patient has to step from lower-rungtreatments up to a specific treatment after failure. Givinglower-level treatment first makes sense only if the patienthas not tried low-end treatment already, and most peoplegoing to a doctor for headache have tried a variety of symp-tomatic treatments, both over the counter and prescription,without success.

The other approach for selecting medication is called strat-ified care, which is the matching of the type of treatment to thepatient or headache characteristics. One way to do this is to

ask how bad the headache attacks are; how quickly they getbad; whether there is nausea, vomiting, or sensitivity to light,noise, and movement; and if the headache impacts on thepatient’s activities of daily living. If a patient has quick onset ofsevere pain with vomiting, then migraine-specific medication,probably in an injection or nasal spray form, is appropriate. Itwould not make sense to prescribe a nonspecific symptomaticmedication to someone so disabled.

Another approach, championed by Prof. Richard Lipton,professor of neurology and public health at Albert EinsteinSchool of Medicine in the Bronx, NY, is to ask how much losttime is caused by the headache. In this approach to stratifiedcare, the time loss serves as a marker for the severity of theheadache. Prof. Lipton has shown in a scientific study compar-ing step care with stratified care that using a migraine-specificmedication such as a triptan from the beginning of treatmentof someone with more than 10 days of some time loss fromtheir migraine attacks over 3 months works better than start-ing with low-end medication and gradually working up.

HOW TO EVALUATE THE SEVERITY OF MIGRAINE

If you have moderate to severe migraine attacks that producedisability, it has been shown that treating with a triptan first,instead of starting with one low-end medication after another,is more reasonable because it saves you time and money in thelong run. Before initiating treatment of your migraine, con-sider two issues: first, how bad your headaches are, and, second,how much time you are losing from them. Ask yourself howsevere the headaches are at their peak intensity, how quicklythey reach peak intensity, whether you have nausea and vom-iting, and how quickly you develop the nausea and vomiting.

Doctors and other health care providers primarily evaluateheadache using intensity of headache pain, headache fre-quency, and the presence of nonheadache symptoms, such as

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nausea; sensitivity to light, sound, and movement; fatigue; andlethargy. Additionally, some patients are asked to keepheadache calendars or diaries, which help them to identifytriggers to migraine and to track headache frequency. How-ever, this type of information does not assess the impact thatheadaches have on your life. Headaches vary among patients,and the impact of migraine may be severely disabling in manypatients. Disabling migraines affect work attendance, workquality, household and family responsibilities, and leisure andsocial activities. Therefore, consideration of the effect thatheadaches have on your life is critical in designing a treatmentplan to reduce migraine disability. Several tools for measuringthe impact of migraine have been developed. The MigraineDisability Assessment Scale (MIDAS) was developed by Prof.Lipton, in New York, with Dr.Walter Stewart, an epidemiolo-gist at the Johns Hopkins Medical School in Baltimore, MD.This questionnaire measures how migraine affects work,home, school, and recreational activities (Figure 9-1).

The following are some distinct benefits of using MIDAS:

• It is easy to use because you can complete the question-naire independently in just a few minutes.

• It is meaningful because disability is measured as days lostin a 3-month period.

• It is valid and reliable.• It improves communication between you and your physician.• It improves the understanding of the burden of migraine.• It helps identify treatment need.• It establishes how much time you are losing to migraine.

The MIDAS questionnaire can be summarized as a way todetermine how many days in the past 3 months you haveoperated at 50% or less capacity at work, school, home, andsocial and recreational activities. If the total is 11 days or more,you have a moderate to high treatment need or moderate to

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MIDAS QUESTIONNAIRE

INSTRUCTIONS: Please answer the following questions about ALL yourheadaches you have had over the last 3 months.

Write your answer in the box next to each question.Write zero if you did not dothe activity in the last 3 months.

1 On how many days in the last 3 months did you miss work orschool because of your headaches?

2 How many days in the last 3 months was your productivity atwork or school reduced by half or more because of yourheadaches? (Do not include days you counted in question 1where you missed work or school.)

3 On how many days in the last 3 months did you not do house-hold work because of your headaches?

4 How many days in the last 3 months was your productivity inhousehold work reduced by half or more because of yourheadaches? (Do not include days you counted in question 3where you did not do household work.)

5 On how many days in the last 3 months did you miss family,social or leisure activities because of your headaches?

Total

A. On how many days in the last 3 months did you have aheadache? (If a headache lasted more than 1 day, count each day.)

B. On a scale of 0–10, on average how painful were these headaches? (Where 0 = no pain at all, and 10 = pain as bad as it can be)

© Innovative Medical Research 1997

Once you have filled in the questionnaire, add up the total number of days fromquestions 1–5 (ignore A and B).

Score range Description Grade0 to 5 Little or infrequent disability Grade I6 to 10 Mild or infrequent disability Grade II11 to 20 Moderate disability Grade III>21 Severe disability Grade IV

DAYS

Figure 9-1: The MIDAS questionnaire. Reproduced with permissionfrom Richard Lipton, MD.

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high disability and should probably use triptans as a first med-ication in treating your acute migraine attacks.

A second test for evaluating the effect of migraine on a per-son is the Headache Impact Test (HIT). HIT uses a computertest available on the Internet at <www.amihealthy.com> and<www.headachetest.com> to describe the impact and severityof your headaches.You can go to the Web site, take the test, andthen download and print the results for your doctor. HIT isnow available as a paper tool as well, the HIT-6 (Figure 9-2).

OPTIONS FOR ACUTE TREATMENT OF LOW-LEVEL MIGRAINE

If you have low treatment need for your headache, that is, ifyou have less than 11 days of at least 50% time loss in the past3 months, simple or combined analgesics may work on yourheadache.

Option 1: Simple AnalgesicsIf caught early in its course, a low-level acute migraine attack canbe treated in much the same way as an episodic tension-typeheadache,with single-agent analgesics such as acetylsalicyclic acid(ASA; Aspirin), acetaminophen (Tylenol), ibuprofen (Motrin,Advil), ketoprofen (Orudis KT), or naproxen sodium (Aleve).

Option 2: Combination AnalgesicsIf you have low treatment need and single-agent analgesics arenot effective, combination medications that contain ASA, acet-aminophen, and caffeine (Excedrin Migraine, Anacin) can betried. If a caffeine-containing combination product is notavailable, try drinking a cup of coffee (which contains 50–100mg of caffeine) to constrict blood vessels and enhance thepain-relieving effect of the analgesic.

Option 3: Stronger Combination MedicationsFor attacks of low treatment need that fail options 1 and 2,treatment is the same as for episodic tension-type headache.

Nonsteroidal anti-inflammatory drugs (NSAIDs),Midrin,orbutalbital-containing medications (Fiorinal, Fioricet,Esgic) maybe helpful. Remember that these lower-level treatments shouldbe used only for low-level migraines that do not cause impactor time loss and that if you have moderate to severe migraines,

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Figure 9-2: Sample Headache Impact Test. Reproduced with permissionfrom GlaxoSmithKline.

you will probably get a better effect with more potentmigraine-specific treatment, such as a triptan.Also, triptans usu-ally work if lower-level treatment does not work for low-levelmigraine because in migraine patients, low-level headaches areprobably low-intensity migraines that resemble tension-typeheadaches but behave like migraine in terms of response totreatment. Finally, these low-level compounds are more likely tocause daily headache, and, in the case of Midrin and Fiorinal-like compounds, are habituating.Because butalbital is so likely tobe overused, it has been banned in Europe and is unavailable inmost of the world.We try very hard to avoid prescribing thesemedications for our patients, and spend large amounts of timetapering people off them due to overuse.

MIGRAINE-SPECIFIC TREATMENT

TriptansThe introduction of sumatriptan (Imitrex in North America,Imigran in Europe) in the early 1990s represented the mostsignificant advance in migraine therapy of all time. Sumatrip-tan rapidly terminates a migraine attack while eliminatingassociated symptoms such as nausea, vomiting, and light andsound sensitivity. It is associated with minimal side effects, hasbrought relief to millions of migraine sufferers worldwide, andhas greatly enhanced their quality of life owing to its effec-tiveness and rapid restoration of ability to function. Sumatrip-tan has, in effect, become the standard against which newerantimigraine drugs are measured.

As a result of sumatriptan’s resounding success, other phar-maceutical companies have developed newer triptans in thehope of offering alternatives for people who do not receiveoptimal results from sumatriptan. As a class, the triptans con-strict blood vessels in the head and reverse inflammationaround blood vessels in the meninges (the brain covering).They may, however, partially constrict other blood vessels on

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occasion and thus should not be given to patients with coro-nary artery disease, stroke, other blood vessel or vascular dis-ease, uncontrolled high blood pressure, and two rare forms ofmigraine known as hemiplegic migraine (migraine with paralysison one side) and basilar-type migraine (associated with poorcoordination and fainting). Those patients with several riskfactors for coronary disease (men over 40 years, women pastmenopause, obese patients, patients with high cholesterol orhigh blood pressure, diabetics, smokers, or those with a familyhistory of coronary disease in a close relative at an early age)should be evaluated by their doctor as to the safety of usingtriptans. The doctor may do tests to ensure that there is nocoronary artery constriction and may even administer thetriptan for the first time in the office. Blood pressure may bemeasured and an electrocardiogram performed prior to andfollowing administration, in addition to monitoring for sideeffects.Any patient reporting chest pain or pressure should becarefully evaluated before continuing to use these drugs,although usually these are benign side effects. Properly pre-scribed for appropriate patients with migraine, the triptansare safe and effective. The side effects of the triptans aregenerally mild and short-lived and include a tingling sensationin the fingers, increased sensitivity to warmth and other stim-uli, generalized warmth, flushing, chest and/or neck pressure,dizziness, drowsiness, and, rarely, chest pain (Table 9-1).

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Table 9-1: Potential Triptan Side Effects

Nuisance Tingling of hand and fingersFlushingWarmthParesthesiaChest and neck pressureDrowsiness or dizziness

Important to tell your doctor Chest pain

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Patients who experience lightheadedness and fatigueshould rest for a short time after dosing.Triptan side effectscan be reduced by taking the medication early in amigraine attack, when the pain is mild. Also, many peopleadjust to the side effects, infrequent as they are, and tell usthat they lessen with time.Although these medications mayeliminate the attack, about 35% of the time the headachemay return within 24 hours with sufficient severity torequire a repeat dose.

What Your Doctor Needs to Know about How Well Your Triptan WorksIn reporting the usefulness of these medications to your doc-tor, you should include the following information:

• How long it takes before you first begin to feel the drugdecreasing the pain

• How much time passes before you feel significant reliefand can return to your usual activities

• How much the pain improved, for example, a 50% or100% improvement (pain free)

• What percentage of the time the drug works well, forexample, 9 of 10 times or less

• In what percentage of attacks the headache returns within24 hours (a recurrent headache)

• If the headache recurs, how long it takes to return• How many of your attacks are treated with a single dose of

medication and no further medication of any kind (this issustained relief)

• If there any side effects

As with any medication prescribed by your doctor, triptansshould be taken only as directed. Maintaining good control ofmigraine can help reduce the need for emergency departmentand physician visits and may improve overall quality of life.Abrief review of information available for each of these medi-cines appears in Table 9-2.

Because several effective triptan medications are available ina variety of delivery systems (tablets, injections, nasal sprays,and preparations that dissolve instantly on your tongue with-out the need for water), do not lose hope if you do notrespond to one preparation or have uncomfortable side effects;you may do well with a different triptan or different deliverysystem—or even the same triptan—for your next attack.

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Table 9-2: Description of the Triptans

Maximum Comes Generic Brand Dose Quantity in in Box Name Name Form (mg) 24 H (mg) of

Group I

Sumatriptan Imitrex Subcutaneous 6 12 2injection

Tablet 25, 50, 100 200/24 9(100 is hoursbest dose)

Nasal spray 5, 20 (20 40 6is best starting dose)

Zolmitriptan Zomig* Tablet 2.5 10 6 (2.5 mg)5 10 3 (5 mg)

Zomig Melt 2.5 10 6 (2.5 mg)ZMT* 5 3 (5 mg)

Zomig* Nasal spray 5 10 6 (5 mg)Rizatriptan Maxalt Tablet, melt 5, 10 (10 is 30 (15 if on 12

best dose; propranolol)5 if on propranolol)

Almotriptan Axert Tablet 12.5 25 6Eletriptan Relpax Tablet 20, 40 (40 is 80 6

best dose)Naratriptan Amerge Tablet 1, 2.5 5 9Frovatriptan Frova Tablet 2.5 7.5 9Dihydroergotamine: Migranal nasal spray 4 sprays,

totaling2 mg

*quick-acting; **slow-acting

Types of tr iptans. Triptans can be divided into two groups:group I, the fast-acting, higher-powered oral triptans, andgroup II, the slower-onset, lower-powered triptans, with possi-bly lower recurrence.The group I triptans includes sumatrip-tan (Imitrex), zolmitriptan (Zomig), rizatriptan (Maxalt),almotriptan (Axert), and eletriptan (Relpax).All are marketedin the United States, and most, but not all, are marketed inother countries.

Sumatriptan (Imitrex/Imigran) is available in three dosageforms: injection, tablet, and nasal spray. Each injection delivers6 mg via an autoinjector, called a Statdose; this is the mostrapid-acting form. Injection can be repeated once after 1 hourif the headache returns with sufficient severity.The maximumdosage is two injections in 24 hours. Seventy percent of thetime, patients feel relief within 1 hour, and over 80% of thetime, within 2 hours.The chance of a headache coming back(recurrence) within 24 hours is 30 to 40%, with an averagetime to recurrence of 14 hours.

In a study conducted by our group at The New EnglandCenter for Headache in Stamford, CT, and published in thejournal Headache, we reported an 84% success rate in the first100 patients who tried this medication in the injectable form.Eighty-one percent of the patients said that it worked betterthan anything they had tried previously for migraine, andmany termed it “a miracle drug.” Forty-six percent of ourpatients had a recurrent headache between 8 and 15 hoursafter the first dose; this was treated effectively with a seconddose. No patient stopped using the drug because of sideeffects. Sumatriptan is available in the United States andCanada in a tablet form at 25, 50, and 100 mg doses.The max-imum dosage is 200 mg in 24 hours. Recently, the formula forthe tablets was changed to a form that rapidly disperses in thestomach, which replaced the old tablets.When a patient takesthe new 100 mg Imitrex tablet early in a migraine attack,

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when the pain is still mild, within the first hour of the onset ofthe attack, the likelihood of being completely pain free at 2hours is 75%.The 100 mg tablet is now considered the bestdose. Sumatriptan nasal spray is available in 5 and 20 mg sin-gle-dose units; the dose is one spray in one nostril. Mostpatients will respond to the 20 mg dose, which works fasterthan a tablet.We recommend spraying it in one nostril withthe head in a neutral position or bent slightly forward andpointing the tip of the sprayer up and in or out but not straightback.When you spray it, do not sniff it in to the back of yourthroat; try to keep it in your nose. Taste disturbance (oftendescribed as a “bad taste”) is the most common side effect, fol-lowed by nausea, vomiting, fatigue, and flushing.

The advantage of sumatriptan is that you can switch fromone form to another in the same day. For example, if youvomit and start out using the shot and need to redose later,you can switch to the tablet or nasal spray.We call this flexibil-ity of form.

Zolmitriptan (Zomig) is available in tablet form in 2.5 and 5mg doses in the United States and some other countries. ZomigZMT 2.5 and 5 mg doses are also available as rapidly melting anddissolving orange-flavored pills or melt tablets that are placed onthe tongue and dissolve within 30 seconds. Up to 67% ofpatients who waited to take the medication until the pain was atleast moderately severe achieved pain relief in 2 hours with the2.5 mg pill. It is safe to take 2.5 or 5 mg to treat the initialmigraine attack and repeat either 2.5 or 5 mg at 2 hours if themigraine persists.With one to two doses, people who respond tozolmitriptan are able to successfully treat 95% of attacks over ayear—a very high consistency.The 5 mg zolmitriptan is morelikely to make a patient pain free than is the 2.5 mg dose, and itis used as a starting dose for many patients.

The orange-flavored Zomig ZMT and orally dissolvablemelt tablets in general are designed to encourage patients to

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take the medication early in an attack because of the conven-ience of the melt formulation. Orally dissolvable tablets arenot absorbed in the mouth or under the tongue; they dissolvein the saliva and go through the gastrointestinal tract, wherethey are absorbed in the small intestine. But because they donot need to be taken with liquid, which can trigger or worsennausea for some, many patients take them earlier in an attackand find them more convenient than and preferable to con-ventional tablets.

Zolmitriptan nasal spray was released in the United States atthe end of 2003 but has been available in Sweden for several years.It is available as a 5 mg unit dose spray, which should be taken atthe start of a headache when it is mild and can be repeated in 2 hours if needed. As with all nasal sprays, it is rapidly absorbedfrom the nasal mucosa right into the bloodstream and then entersthe brain, bypassing the entire gastrointestinal tract. Special studiesusing radioactive-labeled zolmitriptan documented the speed ofabsorption and the distribution in the body and brain. Zomig isfound in the blood in 2 to 5 minutes and in the brain in 5 minutesand begins to work as early as 10 minutes to relieve headache insome patients. Seventy percent of those who waited to takeZomig until their headache was at least moderately severe weresignificantly better by 2 hours. Forty-nine percent of patientsobtained sustained headache relief (the headache did not recur inthe next 24 hours, and no other medications were necessary).Weare always looking for medications that work quickly but keep thepatient better for long periods of time.

Zolmitriptan works well in all migraine types, includingmenstrual migraine and migraine present on awakening. Asnoted above, all of the triptans must be used cautiously inpatients with cardiovascular risk factors. The most commonside effects of zolmitriptan are nausea, dizziness, drowsiness, andtingling in the fingers; these effects are infrequent, mild, andtransient.The recurrence rate for zolmitriptan tablets is about

30% and much less for the nasal spray (about 16%), meaningmost patients take one dose and have relief for the entire day. Inthe United States, the maximum amount of zolmitriptan thatyou should take in 24 hours is 10 mg. Zolmitriptan is the onlyoral triptan found to be effective in aborting cluster headache.Zomig nasal spray looks promising as a treatment for cluster,and we await the results of planned studies.The advent of theZomig nasal spray gives flexibility of form (matching the formof the drug to patient need) to Zomig.

Rizatriptan (Maxalt) is a fast-onset triptan and comes in 5and 10 mg pills and rapidly dissolving tablets (Maxalt MLT—mint-flavored melts). Over 70% of attacks are relieved with the10 mg dose in 2 hours, and many studies have found that riza-triptan is a very rapidly active oral triptan. The maximumamount that you should take in 24 hours is 30 mg. Most ofour patients stop at 20 mg if there is no beneficial effect. Formost patients, 10 mg rizatriptan works better than does 5 mgand is the proper starting dose.There is some evidence that, fortreating migraines that have reached a moderate to severeintensity, rizatriptan is the most likely oral triptan to work aftera single dose, that is, most likely to achieve a sustained pain-free response. If you are taking propranolol (Inderal) formigraine prevention or other reasons, such as high blood pres-sure, you need to use the 5 mg dose of rizatriptan. In thatcase, the maximum amount that you can take in 24 hours is 15 mg, and 10 mg may be enough.

Almotriptan (Axert) is available in a dose of 12.5 mg.Pain relief at 2 hours occurs in about 61%, similar to reliefwith sumatriptan tablets, and its recurrence rate is identicalto that with sumatriptan. However, almotriptan is differentfrom sumatriptan in that it shows slightly fewer nuisanceside effects, so some patients tolerate it better than othergroup I fast-acting oral triptans.The maximum dose per 24hours is 25 mg.

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Eletriptan (Relpax) 20 mg and 40 mg tablets were intro-duced in the United States in 2003. One of the fast-actingtriptans, it has a headache response rate at 2 hours of about65%.The maximum daily dose is 80 mg. Owing to its specificmetabolism, Relpax may not be used within 72 hours of hav-ing stopped seven different medications: two fungal antibiotics(itraconazole and ketoconazole), two acquired immune defi-ciency syndrome (AIDS) drugs (ritonavir, nelfinavir), twoantibiotics (troleandomycin, clarithromycin), and an antide-pressant (nefazodone).

Group II triptans, naratriptan (Amerge) and frovatriptan(Frova), are slower-onset triptans. Naratriptan is available as1 mg and 2.5 mg tablets. It should be used for differentheadaches from those treated with sumatriptan, zolmitriptan,rizatriptan, almotriptan, and eletriptan.These latter five trip-tans are fast acting and can be used at almost any time in theheadache but work better when taken early, when theheadache is mild.The group I fast-acting triptans have a recur-rence rate of 30 to 40%, that is, the headache recurs after suc-cessful treatment about one-third of the time.

Naratriptan is slower in its onset than the five fast-actingtriptans, with 66% of people obtaining headache relief at 4hours. (In general, the triptans of group II take twice as long asthe group I triptans to take effect.) However, if you take nara-triptan early in a migraine (in the first 30 minutes), recurrencecan be low or even zero, and it should be more effective thanwhen taken late in a migraine.When directly compared withsumatriptan and rizatriptan, naratriptan is associated with alower likelihood of the treated migraine recurring.

In addition, the side effects of naratriptan are so minimalthat it is difficult to tell its side effects from placebo (those of asugar pill). It is referred to as the gentle triptan because of its lownuisance side effects. However, as with all triptans, it cannot beused by people with vascular disease.

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Consequently, naratriptan is a good choice if you are sensi-tive to medications, develop your migraines slowly over hours,have long-duration or menstrual migraine, or do not wake upwith a migraine but develop it gradually during the day.Themaximum amount you should take in 24 hours is 5 mg.

Frovatriptan (Frova) is available as a 2.5 mg tablet with aslow onset of action, similar to that of naratriptan, and a 2-hourlikelihood of pain relief of 36 to 46% that increases to 66% at 4hours.Thus, as with naratriptan, it takes about twice as long asdo group I triptans to take effect. It may be a good medicationto try in long-duration or slow-onset attacks or menstrualmigraine and in similar situations as described above for nara-triptan.When taken very early in an attack, it can work quickly.

Although one study found no difference in the recurrencerate of frovatriptan in direct comparison with sumatriptan, inmany other studies the recurrence rates with frovatriptan werevery low—in the teens and even below 10% in one study.These are the lowest rates for recurrence of all of the triptans.The other special attribute of the drug was noticed in one studyin which people were given frovatriptan to use over a year. Itwas found that the one-third of patients who achieved headacherelief by 2 hours maintained this quick response over the entireyear, coupled with a very low (6%) likelihood of the headacherecurring. These lucky patients get a quick “one and done”response from frovatriptan. Thus, frovatriptan may be a usefulmedication for the subset of people who demonstrate both thequick headache relief and the remarkably low recurrence rate.

Summary. Because of the importance of the triptans in treatingthe acute migraine attack, it is worth summarizing how eachone has its own characteristic place in treatment of an individ-ual. Sumatriptan has the highest potency (as an injection),quickest onset (injection and nasal spray), and greatest flexibil-ity of form.Zolmitriptan has the highest consistency over time,has two oral dose forms, has extremely fast-onset (starting in 10

minutes in some patients in double-blind, controlled trials) andlong-lasting relief (as the new 5 mg nasal spray), can be success-fully used in cluster headache, and also demonstrates flexibilityof form. The easy-to-use ZMT or melt form is likely to betaken earlier in an attack. Rizatriptan has a slightly quickeronset of effect than the other available conventional oral triptantablets (although it has not yet been compared with the newrapidly disintegrating tablets, Imitrex), with the greatest likeli-hood of one tablet terminating a moderate to severe attack.Almotriptan has the effectiveness of the old conventional oralsumatriptan, with a slightly more favorable side-effect profile.Eletriptan has a very high effectiveness rate and is another fast-onset alternative. Naratriptan has the gentlest nuisance side-effect profile of them all and a low recurrence rate. Frovatriptaneffectively treats a subset of people, producing consistentlyquick headache relief and very low recurrence rates.

Remember that triptans should not be taken if you haveheart disease or untreated high blood pressure or have had astroke or any type of blood vessel problem. If you have any car-diac risk factors, such as heart disease, obesity, high cholesterol,diabetes, a smoking history, lack of exercise, or age over 40, orhave a family member who has heart disease at a young age, youneed to be evaluated by your doctor before taking a triptan.

Remember, the best triptan for you is the one that worksthe best.A failure to respond to one triptan does not predict afailure to respond to another, nor do side effects from one pre-dict side effects from another. So if your triptan is not doingeverything you want for your migraine, ask your doctor to tryanother one.

ErgotsErgotamine tartrate (Cafergot) has been in use for over 50years as a specific migraine agent.The rectal suppositories arebetter absorbed and more effective than are ergotamine tabletsin the treatment of headache.

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We recommend that one to two ergotamine tablets betaken at the start of a migraine attack, followed by one moretablet in an hour if needed. Ergotamine works best in a non-nauseating dose; if you cannot tolerate a full-coated tablet, youshould use a suppository. Initially, use one-quarter of the sup-pository and repeat in an hour if needed.

Most patients need to pretreat with an antinausea medica-tion before use of either form of ergotamine. Refer to anti-nauseants for recommendations about pretreatment to preventnausea.We instruct patients to use ergotamine preferably only1 day per week and no more than 2 days per week.The onlyexceptions are for women who may need to use it for 3 or 4consecutive days during menstrual periods and for clusterpatients, who may need to use it more frequently.

The side effects of ergotamine include nausea, vomiting,and diarrhea, and some patients experience tingling in the fin-gers and toes, chest pain, and muscle cramps.

DihydroergotamineDihydroergotamine (D.H.E. 45) is chemically related to ergo-tamine tartrate but is more effective and less likely to causenausea. Originally available only as an injectable solution, it isalso available in the nasal spray form, Migranal. The initialinjectable dose is 1 mg, which may be repeated in 2 hours ifneeded. The headache is not likely to recur once it disap-pears.When given intravenously, the dose should be lower tostart—0.25 or 0.5 mg—and should always be preceded by anantinausea medication. For the nasal spray, we recommendone spray in each nostril as an initial dose, to be repeated in15 minutes.These four sprays contain 0.5 mg each for a totaldose of 2 mg. D.H.E. 45 is less likely to cause recurrent orrebound headache than is ergotamine and can be used severaldays per week.The most frequent side effects from the D.H.E.45 nasal spray are occasional stuffiness of the nose, musclecramps, and diarrhea.

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Warning: Patients who take macrolide antibiotics (eryth-romycin, azithromycin [Zithromax], and clarithromycin[Biaxin]) and/or have coronary artery disease, untreatedhypertension, or peripheral vascular disease, or who could bepregnant, should not take D.H.E. or ergotamine. All of theprecautions that apply to triptans also apply to ergots.

Treatment for People Who Cannot Take TriptansFor those with vascular disease or those types of migraine forwhich the US Food and Drug Administration prohibits the useof triptans (basilar-type and hemiplegic migraines; see above),we prescribe a medication that does not affect blood vesselsstrongly, such as an NSAID in prescription-strength doses,(more rarely) or a combination medication. Midrin containsisometheptene,which only very mildly constricts blood vessels,combined with acetaminophen to relieve pain and dichlo-ralphenazone, which is a mild tranquilizer. Fiorinal contains abarbiturate (butalbital), a pain reliever (ASA), and caffeine.Wetry to avoid its use.

Prescription NSAIDs can be helpful in treating a tension-type headache, a mild migraine, and, occasionally, a significantmigraine, especially in those who cannot take a triptan. Referto Table 9-3 for a listing of NSAIDs. Prescription NSAIDsmay work better than those available off the shelf.At The NewEngland Center for Headache, we usually prescribe the fol-lowing: naproxen sodium (Anaprox), ketoprofen (Orudis),meclofenamate (Meclomen), and flurbiprofen (Ansaid).

The standard dosage for prescription NSAIDs is two tabletsor capsules initially, followed by two more in 1 hour if necessary,with a maximum of four per day, 3 days per week. NSAIDsshould be taken with food. Patients taking NSAIDs may expe-rience stomach pain, heartburn, kidney problems, elevatedblood pressure, and gastrointestinal bleeding (watch for dark ortarry stools) and sometimes eye problems and occasionaldrowsiness (with use of indomethacin). Celecoxib (Celebrex)

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Table 9-3: Nonsteroidal Anti-inf lammatory Drugs CommonlyUsed in Migraine and Tension-Type Headache

Generic Name Brand Names Dose (mg) Side Effects CommentsNaproxen Naprosyn 250, 375, 500 Can cause

stomach ulcers,kidney problems,elevated blood pressure, and excessive bleeding

Naproxen sodium Anaprox 275, 550 See aboveNaprelan 375, 500Aleve 220

Diclofenac Cataflam 25, 50, 75, 100 See aboveVoltarenVoltaren-XR

Indomethacin Indocin 25, 50 See above,Indocin SR plus eye

75 SR only problems and occasional drowsiness

Etodolac Lodine 200, 300, 400 Can cause Lodine XL 400, 500, 600 stomach ulcers,

kidney problems,elevated blood pressure, and excessive bleeding

Ibuprofen Advil 200 See aboveMotrin 400, 600, 800

Fenoprofen Nalfon 200, 300 See aboveKetoprofen Orudis KT 12.5 See above

Orudis 25, 50, 75Oruvail 100, 150, 200

Flurbiprofen Ansaid 100 See aboveMefenamic acid Ponstel 250 See aboveNabumetone Relafen 500, 750 See aboveMeclofenamate Meclomen 100, 200 See aboveKetorolac Toradol 10 mg pill, See above, Limited to

30 or 60 mg plus higher max of 5 ampoule for incidence days use;injection of ulcers 1st dose

should beIV or IM,then switchto oral

Celecoxib Celebrex 100, 200 See above, A new but lower cyclo-incidence oxygenase 2 of stomach (Cox-2) problems inhibitor

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100 and 200 mg may cause fewer gastrointestinal problems thando traditional NSAIDs, and may be effective in many types ofheadache. It is taken only once per day.The dose of the combi-nation medicine Midrin is one or two capsules at the start of aheadache, followed by one or two more in 1 hour if theheadache persists. Patients should take no more than five cap-sules in a day, and use of Midrin should be limited to 3 days perweek.The side effects of Midrin include occasional dizziness,drowsiness, or gastrointestinal symptoms. Midrin may be effec-tive early in a mild migraine attack, and it has so few side effectsthat we prescribe it on occasion for older children.

Warning: Dangerous drug interactions can occur ifMidrin is taken with a monoamine oxidase inhibitor (MAOI)antidepressant (see page 85) such as phenelzine (Nardil) ortranylcypromine (Parnate).

If the NSAIDs or Midrin do not provide adequate relief,we sometimes prescribe medications that contain the short-acting barbiturate butalbital. See Table 9-4 for the names,ingredients, and recommended doses of butalbital-containingmedications. If used frequently, any of these medications cancause dependence and rebound headache.Those that containacetaminophen instead of ASA are easier on the stomach buttougher on the liver; combinations that contain codeine aremore potent pain relievers, but they are more likely to producedependency. One or two tablets of butalbital-containing med-ications are the initial dose, and one or two more tablets maybe taken 4 hours later if necessary. Exceeding the daily limitslisted in Table 9-4 may cause rebound headache, dependency,or a “drugged” feeling.

Patients should limit intake to no more than 2 days perweek. Butalbital-containing medications may cause drowsi-ness, poor coordination, and slurred speech.

Warning: Do not drink alcohol, drive, or operate machin-ery after taking medications containing butalbital.

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RESCUE MEDICATIONS

When all else fails, it is sometimes necessary to take medica-tions to dull the pain and help you sleep.These medicationsare not as effective as triptans, which restore you to normalfunction.

OpiatesWe prescribe opiates (narcotics) for our patients as backup res-cue medication only when absolutely necessary.We prefer touse gentle low-level opiates, but even these can cause drowsi-ness and nausea. The low-level opioids include tramadol(Ultram), propoxyphene (Darvon), codeine, and hydrocodone-acetaminophen (Vicodin). Sometimes it is necessary to pre-scribe stronger, more sedating opiates, such as oxycodone(OxyIR, Roxicodone), hydromorphone (Dilaudid), morphine(MSIR), and butorphanol tartrate (Stadol nasal spray).Whenappropriate, we prescribe hydromorphone (Dilaudid) suppos-itory or butorphanol tartrate nasal spray (Stadol NS) becausethey are easy for patients to use, even when vomiting is pres-ent, and permit home treatment of severe pain.We give onlylimited amounts of these medications to prevent overuse anddependency.

Table 9-4: Combination Analgesics Containing Butalbital

Drug/Components Size (mg) Recommended DosageFiorinal 1–2 tablets every 4 hours as needed;

Butalbital 50 no more than 6/day, no more ASA 325 than 2 days/weekCaffeine 40

Fioricet/Esgic 1–2 tablets every 4 hours as needed;Butalbital 50 no more than 6/day, no more Acetaminophen 325 than 2 days/weekCaffeine 40

Phrenilin 1–2 tablets every 4 hours as needed;Butalbital 50 no more than 6/day, no more Acetaminophen 325 than 2 days/week

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Drowsiness is a well-known opiate side effect, so plan tostay home after taking a dose. Because opiates may help yousleep, they are particularly useful for nighttime headaches.Other side effects include nausea, vomiting, and dizziness.

Warning: Butorphanol may inactivate other opiates.Therefore, do not use it if you are on other opiates. Use thismedication with caution if you are taking other medicationsthat cause drowsiness. Overuse of any opiate can causedependency and a drugged feeling. Dosing recommendationsmust be followed carefully, and use must be limited to onedose per week or less.

Antianxiety AgentsMigraine patients with anxiety may feel relief when usingbenzodiazepine minor tranquilizers such as lorazepam (Ati-van), alprazolam (Xanax), diazepam (Valium), and clorazepate(Tranxene).Although these drugs may relieve anxiety and pro-mote relaxation, they can cause dependency and worsenheadache syndromes. Buspirone (Buspar) does not causedependency and can be used daily for treatment of anxiety.

SteroidsDexamethasone (Decadron) and prednisone, which aresteroids, can be used if all else fails.They should be used onlyonce or twice per month because frequent use of steroids canproduce serious side effects.We prescribe a single 4 mg tabletof dexamethasone, which may be repeated in 3 hours if thefirst dose is not effective. Up to 70% of our patients get reliefof their headache from the use of dexamethasone, even after atriptan has failed to help. Occasional use of dexamethasonemay cause reddening of the face, sleeplessness, and a slightincrease in blood pressure. Excessive use should be avoidedbecause it may produce multiple side effects, including loss ofbone strength, ulcers, and joint deterioration.

Warning: Patients with uncontrolled high blood pressure,osteoporosis, diabetes, psychiatric illness, active ulcer disease, oracute infection should avoid the use of steroids.

Antinausea MedicationMigraine can cause nausea, and sometimes antinausea medica-tions (antiemetics) must be used as rescue. Other times, anti-nausea medication taken with antipain medication yields abetter response than does either alone. Antiemetics combatnausea occurring because of migraine or as a side effect of aspecific medication such as ergotamine tartrate (Cafergot).

Antiemetics that may help include promethazine (Phener-gan),metoclopramide (Reglan), prochlorperazine (Compazine),trimethobenzamide (Tigan), chlorpromazine (Thorazine),hydroxyzine (Vistaril), and an off-the-shelf liquid preparation,Emetrol. Emetrol can be added to any of the previously men-tioned antinauseants and can be repeated every 15 to 30 min-utes. The newer antinauseants, ondansetron (Zofran) andgranisetron (Kytril), are also extremely effective.

The antinausea medications we prefer to prescribe arepromethazine (Phenergan), taken by mouth or as a supposi-tory, and oral metoclopramide (Reglan). Promethazine is morelikely than is metoclopramide to make you drowsy and helpyou sleep; metoclopramide keeps you alert but can occasion-ally cause mild agitation. If you need to be alert so that youcan go to work, we recommend that you use metoclopramideabout 15 minutes before taking an ergotamine-type medica-tion. If you prefer to sleep and can remain at home, prome-thazine is the preferred choice. Prochlorperazine (Compazine)may be helpful, but some patients may experience musclespasms when using it. Of all of the traditional antinausea med-ications, promethazine is the most useful for rescue and sleep,and metoclopramide is the most useful to add to other med-ications during the day. Ondansetron (Zofran) is a differenttype of antinausea medication that is helpful in treating the

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nausea of migraine, and it almost never causes drowsiness. Itis available as a tablet, a melt, and an intravenous injection.Granisetron (Kytril) is available as a 1 mg tablet and by intra-venous injection.

Miscellaneous TreatmentsOther medications for headache include muscle relaxants suchas carisoprodol (Soma), methocarbamol (Robaxin), cycloben-zaprine hydrochloride (Flexeril), and metaxalone (Skelaxin).Diazepam (Valium) and clonazepam (Klonopin) are also usedas anticonvulsants and may be beneficial for patients whoseheadaches are associated with neck pain, muscle spasm, andanxiety. Baclofen (Lioresal) and tizanidine (Zanaflex) arehighly potent antispasticity drugs typically used in patientswith cerebral palsy and multiple sclerosis.They may be helpfulin some patients with tension-type headaches and musclespasm. Tizanidine has been tested recently in patients withchronic daily headache and is helpful when sleeping is diffi-cult, but it does require blood tests periodically for safety.

The problem with all of these medications is that they arenonspecific, create drowsiness, and can be habituating. Patientswith neck pain and headache usually have migraine and arebetter off using triptans than any of the long list of “muscle-relaxing” medications.

TENSION-TYPE HEADACHE VERSUS MIGRAINE: HOW TO KNOW WHICH TO TREAT

For many years, headache specialists thought that we shouldtreat tension-type headaches one way and migraine another.Now we know that most people with migraine have a spec-trum of headaches, from those similar to tension-type headacheto those that are obviously migraine. About 75% of attacks oflow-level migraine initially seem to be tension-type headachebut end up being disabling migraine. It is the wrong approach

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to treat them with low-level or over-the-counter medicationsand rescue with triptans when the attacks become very bad.For this reason, we have stopped recommending treating thelow-level tension-type attacks in migraine patients with low-level treatment; most of the attacks end up moderate to severeand disabling, and triptans work better if taken when the pain ismild (see the following section). Also, if the triptan is takenlater, there is a lower likelihood of becoming pain free and agreater likelihood that the headache will recur. Finally, whenthe triptans are taken early, the nuisance side effects are less.

So, our recommendation to patients with disablingmigraines is to take the triptan early in the attack, at mild pain,and not to wait or treat with a lower-end medication first. Ifyou become pain free with a triptan and the migraine doesnot recur, you will actually use fewer, not more, triptan tabletsover time.

Why Treat Early?The concept of allodynia has been well known in the field ofpain and has been introduced to the world of headache andstudied extensively and elegantly by Dr. Rami Burstein atHarvard in Boston. First, let us understand and define twobasic concepts: sensitization and allodynia.

SENSITIZATION

This occurs when a nerve cell that carries sensory informationabout the environment from the periphery such as the skin ofthe head or the coverings of the brain sends its signal into thebrainstem. Here a connection is made with a second neuron,which, in turn, carries the information to the major pain-per-ceiving part of the brain, the thalamus.There another connec-tion (synapse) is made to a third neuron carrying informationto the top of the brain, where pain finally reaches conscious-ness, the cortex.

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“Sensitization” means that a nerve cell fires too easily whenit receives a stimulus from the environment. Think about asunburn. Because of tissue damage and inflammation from thesun, our skin is more sensitive to touch, and normal touchbecomes painful.

Now back to migraine: instead of skin, we are dealing withthe coverings of the brain, the meninges, which becomeinflamed during the migraine process.The nerves that tell thebrain that the meninges are inflamed become sensitized. If amigraine patient shakes her head between attacks, this is notpainful. But a migraine patient would not dare do this duringan attack because it would hurt too much.The nerves carryingthe signal into the brain, as well as the nerves within the brain,have become sensitized to all stimuli—touch, movement, light,almost everying.Therefore, mild stimuli are uncomfortable tothe migraine patient.

ALLODYNIA

Allodynia is the state that occurs when nonpainful stimuli areexperienced as painful.The longer a migraine attack goes on,the more the nerves are activated in the brainstem.At the peakof a migraine, everything hurts—light, noise, touch, smells, andmovement. Patients experience pain with a variety of normalstimuli, even a shower or combining their hair, and they maynotice this sensitivity even beyond the head, in the arms or legs.

As noted above, all of the triptans appear to work better iftaken during the mild phase of a migraine attack. Once all ofthe nerves are activated and sensitized, and once allodyniaoccurs with the sensation that everything hurts, the triptans donot work as well in terminating a migraine attack. Dr. Bursteintells us that 80% of migraine patients develop allodynia, andthose who do will not do well unless they take their medica-tion before the development of this sensitivity to light, noise,and touch. He states that it is best to take the triptan in the first

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20 to 30 minutes of a migraine attack. Early treatment of anattack with a triptan improves outcomes and prevents disability.

The exception to this is when migraines are too frequent totreat early or when a person has many different intensities ofattacks. For this reason, we recommend restricting triptan useto no more than 2 or 3 days per week. If the migraine fre-quency is higher than that, a preventive daily medicationbecomes necessary to reduce the frequency of attacks and allowfor early treatment again with the triptan. The use of dailymedications to prevent migraine is discussed in Chapter 10.

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When two or more severe migraine attacks occur per week,and if each attack lasts for more than 24 hours or if attacks aredifficult to treat with the symptomatic and specific acute caremigraine medications mentioned in Chapter 9, then daily pre-ventive medications should be taken to decrease or blockmigraine attacks. Other reasons to use preventive medicationsare when there are contraindications to using triptans, too manyside effects from triptans or patients using acute care medica-tions like triptans or analgesics more than 3 times per week.There are no rules as to which preventative medications to startwith, but we tend to look at what other problems a patient hasand choose a drug to help both the headache and the otherproblem (antidepressants work on headache and depression, betablockers work on headache and hypertension, etc). Several cat-egories of medications can be used (Table 10-1); some patientsdo better with one type of medication than with another.

BETA-BLOCKERS

Beta-blockers (b-blockers) may work by stabilizing arteries orpreventing the central generator of migraine in the brainstemfrom firing. Of the many b-blockers, propranolol (Inderal),atenolol (Tenormin), metoprolol (Lopressor, Toprol XL),nadolol (Corgard), and timolol (Blocadren) are the most effec-tive for prevention of migraine.Those we prescribe most fre-quently are metoprolol, atenolol, nadolol, and propranolol.

Our patients take metoprolol (Toprol XL) 50 mg oncedaily, increasing to 100 mg if necessary, or propranolol 10 to 20mg twice a day, increasing by 10 to 20 mg every 5 days up to adose of about 60 to 120 mg. If a patient does well on short-act-ing propranolol in divided doses, we may then switch to the

PREVENTIVE TREATMENT OF MIGRAINE WITH MEDICATION

CHAPTER 10

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Table 10-1: Preventive Treatment of Migraine

Dosage Generic Trade Range Name Name (mg/day) Side Effects

b-BlockersPropranolol Inderal 20–360 Fatigue, depression, weight

gain, asthma, impotence,reduced blood pressureand pulse rate, dizziness,reduced tolerance tophysical activity, cold hands

NOT for use by diabetics or asthmatics

Metoprolol Toprol XL, 50–100 Fatigue, depression, weight Lopressor gain, asthma, impotence,

reduced blood pressureand pulse rate, dizziness,reduced tolerance tophysical activity, cold hands

NOT for use by diabetics or asthmatics

Nadolol Corgard 20–160 Fatigue, depression, weight gain, asthma, impotence,reduced blood pressureand pulse rate, dizziness,reduced tolerance tophysical activity, cold hands

NOT for use by diabetics or asthmatics

Timolol Blocadren 10–40 Fatigue, depression, weight gain, asthma, impotence,reduced blood pressureand pulse rate, dizziness,reduced tolerance tophysical activity, cold hands

NOT for use by diabetics or asthmatics

Atenolol Tenormin 25–100 Fatigue, depression, weight gain, asthma, impotence,reduced blood pressureand pulse rate, dizziness,reduced tolerance tophysical activity, cold hands

NOT for use by diabetics or asthmatics

Continued

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Table 10-1: Continued

Dosage Generic Trade Range Name Name (mg/day) Side Effects

Calcium channel blockersVerapamil Calan, 80–480 Reduced blood pressure and

Covera, pulse rate, constipation,Isoptin, altered heart rhythm,Verelan foot swelling

Diltiazem Cardizem, 60–360 Reduced blood pressure and Tiazac pulse rate, constipation,

altered heart rhythm,foot swelling

Amlodipine Norvasc 2.5–10 Reduced blood pressure and pulse rate, altered heartrhythm, foot swelling

Nisoldipine Sular 10–40 Reduced blood pressure and pulse rate, altered heartrhythm, foot swelling

Flunarizine Sibelium 5–10 Weight gain, depression(available only CAUTION with use inin Canada patients with cardiac diseaseand Europe)

AntidepressantsSee Table 10-2

Antiepilepsy drugs None are for use by women who are or may be pregnantDivalproex Depakote 500 – 1,500 Drowsiness, hair loss, tremor,sodium diarrhea, weight gain,

foot swelling, inflammationof liver, bone marrow, or pancreas

Not for use in people with liver disease or in combination with barbiturates

Gabapentin Neurontin 600 – 2,700 Drowsiness, dizziness,weight gain

Topiramate Topamax 45 – 200 Weight loss, confusion,kidney problems and stones, glaucoma, loss of sweating, tingling of arms and legs

Zonisamide Zonegran 25 – 400 Weight loss, drowsiness,kidney problems and stones, tingling of arms and legs, lack of sweating

Continued

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longer-acting form.Atenolol is usually started at 25 mg in themorning and can be slowly raised to 50 to 100 mg. Potentialside effects of b-blockers include fatigue, asthma, depression,impotence, reduced blood pressure and pulse rate, weight gain,reduced tolerance to physical activity, and dizziness on standing.

Warning: b-Blockers should not be given to people withasthma, diabetes, low blood sugar (hypoglycemia), slow heartrate, low blood pressure, or severe depression.They should alsonot be used in severe cases of migraine accompanied by weak-ness on one side of the body or other evidence of focal braindysfunction. Patients who need to stop taking b-blockersshould taper the dosage gradually over several days to prevent

Table 10-1: Continued

Dosage Generic Trade Range Name Name (mg/day) Side Effects

Tiagabine Gabitril 8 – 48 Drowsiness, nauseaPregabalin Lyrica 150 - 600 Drowsiness, dizziness,

peripheral edema, weight gain, xerostomia, tremor,myoclonus

Lamotrigine Lamictal 100 - 200 Rash, nausea, Stevens Johnson Syndrome (SJS) associated with rapid dose escalation, starting dose of 25 mg recommended

Serotonin2 antagonistsCyproheptadine Periactin 4–16 Drowsiness, dry mouth,

constipation, weight gainMethylergonovine Methergine 0.2–1.2 Drowsiness, stomach upset,

cold limbsNOT to be used longer than

6 months and not to be usedin people with vasculardisease, inflammation in legveins, or stomach ulcers or inpeople taking triptans

Nonsteroidal anti-inflammatory drugsSee Table 9-3

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a withdrawal reaction, including a rapid heartbeat. Patients onpropranolol who use the triptan rizatriptan (Maxalt) shoulduse only a 5 mg dose of rizatriptan.

ANTIDEPRESSANTS

Antidepressant drugs,which increase serotonin levels, are amongthe best medications to treat migraine preventively. Drugs from

Table 10-2: Antidepressants

Generic Name Brand Names

TTrriiccyycclliicc AAnnttiiddeepprreessssaannttssAmitriptyline ElavilDoxepin Sinequan,AdapineNortriptyline PamelorDesipramine NorpraminTrazodone DesyrelImipramine TofranilAmoxapine AsendinProtriptyline VivactilMaprotiline LudiomilClomipramine Anaframil

SSeelleeccttiivvee SSeerroottoonniinn RReeuuppttaakkee IInnhhiibbiittoorrssCitalopram CelexaEscitalopram LexaproFluoxetine ProzacFluvoxamine LuvoxSertraline ZoloftParoxetine Paxil

SSeerroottoonniinn NNoorreeppiinneepphhrriinnee RReeuuppttaakkee IInnhhiibbiittoorrssVenlafaxine EffexorDuloxetine Cymbalta

MMiisscceellllaanneeoouussBupropion WellbutrinMirtazapine RemeronNefazodone Serzone

MMoonnooaammiinnee OOxxiiddaassee IInnhhiibbiittoorrssPhenelzine NardilIsocarboxazid MarplanTranylcypromine Parnate

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each of the three major categories, the tricyclic antidepressants(TCAs) and tetracyclic antidepressants, the selective serotoninreuptake inhibitors (SSRIs), and the monoamine oxidaseinhibitors (MAOIs), may be effective for these headaches.Anti-depressants (Table 10-2) should be chosen both for their abilityto increase serotonin levels and for other effects, such as drowsi-ness or stimulation, that may be helpful for some patients.

TRICYCLIC ANTIDEPRESSANTS

Amitriptyline (Elavil) has been the gold standard for treatmentof chronic headache, but its use may be limited by some of itsside effects.

We prescribe antidepressants for patients with migraine(and also for chronic tension-type headache) as follows:

• For patients who have trouble sleeping through the night,awaken early in the morning, and who may be depressed:amitriptyline, doxepin (Sinequan), or trazodone (Desyrel),which is neither a TCA nor an SSRI

• For patients who require less sedation:TCAs including nor-triptyline (Pamelor), desipramine (Norpramin), imipramine(Tofranil), and protriptyline (Vivactil), the last two of whichhave the least sedating effects and can be given in the morning

Two to 4 weeks of treatment may be required before patientsnotice an improvement in their headaches. Amitriptyline, nor-triptyline, and doxepin are started at 10 mg, 1 to 2 hours beforebedtime, and are raised 10 mg every week, until a total of 50 mgor five capsules or tablets is reached.This is an average dose; itmay have to be adjusted up or down.All medications are startedat low doses and raised gradually to avoid side effects.

All TCAs have possible side effects, the most distressing ofwhich are increased appetite, weight gain, drowsiness in themorning, dry mouth, and constipation. Blurred vision, sexualdysfunction, and urinary hesitancy occur less frequently.

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Warning: Do not use TCAs if you have heart problems,heart rhythm irregularities, or glaucoma or experience diffi-culty urinating.

SELECTIVE SEROTONIN REUPTAKE INHIBITORS

The most frequently prescribed SSRIs are fluoxetine (Prozac),sertraline (Zoloft), paroxetine (Paxil), escitalopram (Lexapro),and citalopram (Celexa). SSRIs tend to have fewer side effectsthan the TCAs and are less likely to cause drowsiness andweight gain.They work well in chronic tension-type headachebut, unfortunately, are rarely effective in preventing or reduc-ing the frequency of migraine. Rarely, they can actuallyincrease migraine.

A patient taking fluoxetine would start with 10 mg eachmorning for 1 to 2 weeks, after which the dose could beraised to 20 mg if no side effects occurred. Maximum benefitbegins to occur between 3 and 6 weeks, and few peopleexperience significant side effects. Higher doses may be nec-essary. Fluoxetine is long acting and remains in the body fordays after it has been discontinued. Prozac has recentlybecome available in a 90 mg pill that lasts for a week, calledProzac Weekly.

Mild agitation or hyperactivity shortly following themorning dose is the most common side effect associated withthe SSRIs; this effect usually stops occurring within 2 weeks.Insomnia, tremor, and difficulty having an orgasm or othersexual dysfunction may occur. On rare occasions, SSRIs canmake patients feel “off ” psychologically or may cause depres-sion or an increase in headache. Patients who notice drowsi-ness should take SSRIs at night.Weight loss is more commonthan is weight gain, although either may occur.

Warning: SSRIs should be used cautiously in severelydepressed patients and must not be used with MAOIs (see thefollowing section).

SEROTONIN NOREPINEPHRINE INHIBITORS

There are two SNRIs available in the US, venlafaxine (Effexor)and duloxetine (Cymbalta).There is scientific evidence for effec-tiveness of venlafaxine in the prevention of migraine.Venlafaxinecan cause the same side effects as SSRIs, with a greater risk ofincreased blood pressure, but the fact that there are data support-ing its use in migraine gives it an advantage over the other non-tricyclic antidepressants in migraine prevention.

Divalproex sodium (Depakote in the United States, Epival inCanada) effectively reduces the frequency of migraine in manypatients and has been approved by the US Food and DrugAdministration (FDA) as safe and effective in the prevention ofmigraine. It is also available in the United States in a convenientlong-acting form, Depakote ER. Other anticonvulsants, such asphenytoin (Dilantin) and carbamazepine (Tegretol), have notbeen as effective.

Divalproex SodiumIf started at low doses and increased slowly over time, dival-proex sodium is less likely to cause side effects. It is safer foruse in adults than in young children. We have adult patientsstart with 125 mg of divalproex sodium once per day andslowly increase the dose until they switch to Depakote ER(extended release), which is taken in a single daily dose of 500or 1,000 mg. Some physicians start patients on Depakote ER250 mg at night.This form of Depakote may cause fewer sideeffects than the short-acting form. At the doses necessary totreat epilepsy or manic-depressive illness, divalproex sodiummay frequently cause significant side effects.At the lower dosesused for preventing migraine, the side effects are far less fre-quent.The high-dose side effects include the breakage of hairshafts on brushing (which could lead to slight thinning ofhair), drowsiness, tremor, weight gain, nausea, diarrhea, andfoot swelling. Occasional blood tests should be performed to

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make certain that liver, pancreatic, and kidney function andcomplete blood count remain normal.

Warning: Women who are pregnant or who may becomepregnant should not take divalproex sodium because it cancause serious spinal cord defects in the fetus.This drug shouldnot be used in anyone with liver disease and should be givencautiously to young children. It should be used cautiously incombination with barbiturates such as phenobarbital andbutalbital-containing medications (such as Fiorinal). Finally,because of the concern over the effects of divalproex on thefetus, before prescribing this drug to a woman of childbearingage, a serious discussion should occur between doctor andpatient.The patient should be given daily folic acid.

GabapentinGabapentin (Neurontin) is also an effective migraine preventiveagent. It has a safer side-effect profile than does divalproexsodium,but it is less convenient to use because it must be takenat least three times a day.The main side effects are drowsiness,dizziness, and, occasionally, weight gain. No blood tests arerequired with use of gabapentin. Gabapentin should also bestarted at a low dose, at 100 to 300 mg at night, although stud-ies suggest that a total of 1,800 to 2,400 mg per day in divideddoses three times per day is optimal for prevention of migraine.

TopiramateTopiramate (Topamax) has been established recently as effectivein preventing migraine, and the FDA is set to approve its useofficially as safe and effective in migraine prevention.Topiramateis often sought by patients because of its association with weightloss. However, the likelihood of side effects with topiramate usemay increase with the likelihood of weight loss.Topiramate sideeffects include tingling of hands and feet, kidney problems, kid-ney stones, glaucoma, weight loss, decreased sweating, and, mosttroublesome, memory loss or speech problems.We have found

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in our headache center that we can reduce the likelihood ofmost side effects by using a very small dose initially and increas-ing the dose very slowly.Tingling of hands and feet often occursand then disappears. We begin patients with half of the adultdose, 12.5 mg, and increase by 12.5 mg per week until achiev-ing a dose of 50 to 100 mg.We may see the patient at about 1month into treatment, when the dose is around 50 mg. Recentstudies suggest that a dosage of 100 mg per day is clearly effec-tive. If the dosage of 75 to 100 mg per day is reached withoutsignificant side effects, then higher doses are not usually a prob-lem.The FDA has suggested blood tests for kidney function atthe beginning of treatment, at 1 month into treatment, and sev-eral times per year.These tests are to make sure that patients donot develop significant acidosis, a condition that is associatedwith severe fatigue and confusion and that can be dangerous.Most patients tolerate topiramate well.

Other AnticonvulsantsLevetiracetam (Keppra), zonisamide (Zonegran), and some oth-ers have shown some promise and are being studied currently.

CALCIUM CHANNEL BLOCKERS

Calcium channel blockers prevent calcium from entering cer-tain cells in the brain and muscles. Calcium may disrupt nervecells, causing them to fire, inducing aura and migraine.The mostwidely used calcium channel blocker for migraine in the UnitedStates is verapamil (Calan, Isoptin), followed by amlodipine(Norvasc) and diltiazem (Cardizem). Others, such as nisoldipine(Sular), nicardipine (Cardene), and flunarizine (Sibelium, avail-able only in Canada and Europe), may also be used.

Verapamil is usually started with a slow-release form of 120to 240 mg per day.Constipation and fluid retention are the mostcommon side effects of calcium channel blockers; heart effects,low blood pressure, drowsiness, and dizziness may also occur.

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Warning: Patients with significant cardiac problems shouldnot use calcium channel blockers; those who take other bloodpressure medications—especially b-blockers—should usethem with caution.

BOTULINUM TOXIN INJECTIONS

Botulinum toxin (Botox, Myobloc) recently has been reportedas helpful in preventing chronic daily headache. Small dosesare injected in the head and/or neck every 3 months, and theeffect of the drug on migraine frequency or severity usually isobvious by 2–4 weeks.

The only side effect of botulinum toxin injection is a raredroopy eyelid; this effect is dependent on where the injectionsare placed and lasts only a week or two if it occurs.Thus, theadvantages of botulinum toxin injection in preventing chronicdaily headache are that it does not require daily dosage and hasvery few side effects. In fact, botulinum toxin injection is sosafe that the FDA recently approved it in the cosmetic treat-ment of wrinkles.The disadvantage is that it requires injectionsabout every 3 months.

SEROTONIN2 ANTAGONISTS

CyproheptadineCyproheptadine (Periactin) is an antihistamine that blocks sero-tonin2 receptors. It is somewhat effective in preventing migraineattacks in children but less so in adults.Cyproheptadine is availablein tablets and liquid form.The starting dose is one-quarter of a 4mg tablet (1 mg) 1 to 2 hours before bedtime; the dose can beslowly increased to a total of two to four tablets.Children toleratecyproheptadine well and experience few side effects.Adults,how-ever,may become drowsy or have increased appetite with weightgain.Drowsiness may be beneficial for patients who sleep poorly.Some people with nasal problems appreciate its drying effect.

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Warning: Patients who take MAOIs (see page 85) or whohave glaucoma, an enlarged prostate, or obstruction of thebladder should not take cyproheptadine. Cyproheptadine maynegate the beneficial effects of the antidepressants, and it isnot to be used in breast-feeding women, although it appears tobe safe in pregnancy.

Methysergide (Sansert) was recently taken off the market.Ametabolite, methylergonovine, is described below.

MethylergonovineMethylergonovine (Methergine) is an ergot that works bothby blocking serotonin2 receptors and by constricting bloodvessels and can be taken daily for prevention of migraine.Thestarting dosage for methylergonovine is a 0.2 mg tablet onceper day; this is slowly increased to three times per day. Themaximum dosage is usually two tablets three times per day.Possible side effects include muscle aches (cramps in women),hallucinations (rarely), and signs of constricted blood vessels(such as chest pain).

Warning: Methylergonovine should not be used by any-one with heart disease, arterial disease, vein disease, high bloodpressure, or the possibility of pregnancy; it should not be takencontinuously for more than 6 months without a “drug holi-day.” It should not be used in the same day as a triptan.Thus,for patients on methyergonovine for prevention, as-neededtreatment is more limited.

NONSTEROIDAL ANTI-INFLAMMATORY DRUGS

The nonsteroidal anti-inflammatory drugs (NSAIDs) can betaken up to three times a day with food to help decrease thefrequency of migraine (see Table 9-3). They may be highlyeffective, even when other drugs have not worked. Patientsshould be alert for stomach pain because they can cause ulcersor exacerbate reflux. These medications may work well for

women whose migraines increase during menstrual periodsor ovulation because the drugs inhibit the production ofprostaglandins, which cause inflammation and pain. A newform of anti-inflammatories, the cyclo-oxygenase 2 (Cox-2)inhibitors, is being studied in the acute and preventive treat-ment of migraine. The Cox-2 inhibitors, including the newanti-inflammatory medication celecoxib (Celebrex), are lesslikely to cause stomach problems, such as ulcers, than the olderNSAIDs (see page 71).

HORMONAL TREATMENT

Hormonal regulation and other techniques have been tried inwomen whose headaches occur mostly around their menstrualperiods or when they ovulate. For a further discussion ofheadache and the menstrual cycle, see Chapter 16.

LEUKOTRIENE ANTAGONISTS

Leukotriene antagonists are antiasthma medications.The mostcommonly used are montelukast (Singulair) and zafirlukast(Accolate). A study performed at The New England Centerfor Headache suggests that these safe medications may alsoprevent migraine, especially in children.

ATYPICAL ANTIPSYCHOTIC MEDICATIONS

Do not let the word psychotic put you off.These medicationsintervene with another important chemical messengerinvolved in migraine, dopamine.There is anecdotal evidencethat they can be helpful in chronic daily headache unrespon-sive to the usual agents.These medications include quetiapine(Seroquel), olanzapine (Zyprexa), risperdal (Risperidone), andziprasidone (Geodon). Each has advantages and disadvantages,depending on the clinical picture. Quetiapine is very helpful asa sleeping aid in headache patients who do not sleep well.

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Dr. David Dodick, a neurologist and headache specialist atthe Mayo Clinic in Scottsdale, AZ, has divided treatment ofcluster headache into four categories: acute, transitional, pre-ventive, and surgical.

ACUTE TREATMENT

OxygenA cluster headache attack is best treated by breathing pure oxy-gen for up to 20 minutes at a rate of 7 L per hour through aloosely fitting mask that covers the mouth and nose. Relief canbe dramatic! We recommend that patients sit on comfortablefurniture, bending forward at the waist.This is often referred toas the Rodin Thinker position, after the famous sculpture.Thecluster attack usually breaks in 20 minutes or less. The treat-ment can be repeated. In some cases, the oxygen lessens thepain, but the pain recurs when the oxygen is stopped. Oxygenworks better when preventive treatment is being taken.

TriptansA cluster headache can be stopped rapidly with a self-admin-istered injection under the skin of sumatriptan (Imitrex) 6 mg,the only triptan formally studied and approved by the USFood and Drug Administration as safe and effective.The injec-tion generally works in under 15 minutes and occasionally asquickly as 5 minutes, faster than oxygen. Recently, sumatriptannasal spray 20 mg has been found to be effective in stopping acluster attack acutely. It works at the same rate as does oxygen.The maximum approved number of sumatriptan shots orsprays per day is two shots or two sprays, or one of each. SeeChapter 9 for details about side effects.

TREATMENT OF CLUSTER HEADACHE WITH MEDICATION

CHAPTER 11

Zolmitriptan tablets 5 to 10 mg have been shown to stopcluster pain in 30 minutes or less.So far, this is the only oral tabletthat has been found to stop a cluster attack.The study proving itseffectiveness was done in people whose cluster attacks lasted forat least 45 minutes. There are ongoing clinical studies ofzolmitriptan nasal spray that look promising. ery recently, Dr.Alan Rapoport, Professor of Neurology of the David GeffenSchool of Medicine at UCLA in Los Angeles, California, andseveral other authors demonstrated that 5 mg of zolmitriptannasal spray was effective in cluster headache. In the study, somepatients were pain free in 10 minutes if they used 10 mg.

ErgotsErgotamine tartrate can be given by mouth or as a rectal sup-pository (Cafergot) to stop an attack. An injection of dihy-droergotamine (D.H.E. 45) is often helpful, and some patientsuse the D.H.E. nasal spray Migranal. D.H.E. 45 works rapidlyintravenously to terminate almost all cluster attacks.

Other Options Use of opiates is not recommended, first because they do notwork very well in cluster and second because of the risk ofdependency in cluster because the attacks occur daily. Arecent report cites the effectiveness of olanzapine (Zyprexa), anantipsychotic medication, in relieving nighttime attacks.

TRANSITIONAL TREATMENT

Treatment of cluster headache with a steroid is a means torelieve pain while establishing longer-acting preventive treat-ment. Steroids work rapidly to terminate cluster attacks, butthey cannot be used long term because of side effects. Pred-nisone is started at 60 mg per day and tapered gradually tonothing over a period of 10 days to 3 weeks. If, however, thecluster period has not ended when the steroid dose has

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decreased to a critically low level and traditional preventivemedications have not been started, the cluster headaches usu-ally return. Thus, the steroids and the preventive treatmentshould be started simultaneously.We have decreased the lengthof our steroid treatment from 3 weeks to 7 to 10 days todecrease the likelihood of the patient developing one of theserious side effects of long-term steroid use called aseptic necro-sis of bone.This problem affects large joints such as the shoulderor hip and may necessitate a joint replacement.This is a veryrare but serious side effect that can be decreased by shorteningthe treatment time.

Warning: Long-term use of prednisone (or any steroid)may cause the above or numerous other side effects and shouldbe avoided.

PREVENTIVE TREATMENT

Verapamil, a calcium channel blocker, appears at present to bethe most effective preventive treatment for cluster headache.The dosage is an 80 mg tablet taken three times per day; fourto six such tablets (and rarely more) per day are occasionallyrequired. Some patients are able to take the long-acting formof the pill twice per day, but we always start with the short-acting form. See Chapter 10 for details about the side effects.

Ergotamine tartrate, one tablet once or twice per day forseveral weeks, may prevent attacks from occurring; keep inmind that this treatment is not used as a daily treatment inmigraine because it increases the frequency of migraine attacksby causing a rebound syndrome.Also, if a patient takes ergota-mine, he or she cannot take sumatriptan or zolmitriptan in thesame 24 hours. See Chapter 9 for details about side effects.

Lithium carbonate may also prevent cluster headache; 300mg two or three times per day usually brings relief. Lithiumcan cause dry mouth and kidney and thyroid problems andrequires blood monitoring.

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Divalproex sodium (Depakote) prevents cluster headachein some patients.We start our patients on 250 mg two or threetimes daily; then, if possible, we switch them to Depakote ER500 mg in a once-daily dose, increasing to 1,000 mg if neces-sary. See Chapter 10 for details about side effects.

Topiramate (Topamax) appears to be effective in prevent-ing cluster. Doses higher than 75 to 150 mg are rarely neces-sary. See Chapter 10 for details about side effects.

Gabapentin (Neurontin) is another anticonvulsant that maybe effective in preventing cluster at dosages of 1,800 mg perday or higher. See Chapter 10 for details about side effects.Methylergonovine (Methergine) 0.2 mg three times per daycan be taken daily to prevent cluster headache for up to 6months. On rare occasions, the dosage must be doubled.

Once again, if a person is taking methylergonovine, he orshe cannot take a triptan. See Chapter 10 for details about theside effects of methylergonovine.

Other OptionsOne important feature of preventing cluster is that preventivemedications for cluster often work better when combined.Werefer to this treatment combination as verapamil plus.We beginour patients on verapamil and then add some combination oflithium and/or an antiepilepsy drug (anticonvulsant).

When no other medications have worked, indomethacin(Indocin), a nonsteroidal anti-inflammatory drug, can occa-sionally be helpful in some patients with cluster headache.Patients start at 25 mg three times per day with meals;indomethacin must be used with caution to reduce the risk ofulcer.We therefore add an acid-decreasing medication called aproton pump inhibitor, such as omeprazole (Prilosec), lansopra-zole (Prevacid), pantoprazole (Protonix), or esomeprazole(Nexium), to protect the stomach from daily use ofindomethacin. There are headaches that are very similar in

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symptoms to cluster, the paroxysmal hemicranias, that alwaysrespond to indomethacin (see Chapter 3).

Some patients respond to acetazolamide (Diamox), whichis related to topiramate, starting at 250 mg three times per day.

Capsaicin, an extract of red peppers, was investigated as acluster headache preventive medicine by Dr. David Markswhen he worked at The New England Center for Headache.The results suggest that it can help reduce pain after about 5days of daily application inside the nostril on the side of thepain. It is available without prescription as Zostrix HP(0.075%) but should be used only under a doctor’s direction.

Civamide, a synthetic compound that is chemically relatedto capsaicin, may also be effective in preventing cluster. Ongo-ing studies of a civamide nasal spray given in both nostrilsappear promising.

Melatonin levels have been found to be low in patientswith cluster headache, and there are some reports that takingup to 15 mg of melatonin daily may be helpful.

Patients with severe cluster headache who do not respondto outpatient therapy should be admitted to a specialized inpa-tient headache unit for more aggressive care, which usuallyincludes intravenous D.H.E. 45. It almost always works. Anolder, sometimes effective therapy is intravenous histaminedesensitization. It must be given cautiously because intra-venous histamine can precipitate a severe cluster attack.

SURGICAL TREATMENT

Two surgical approaches to an intractable cluster headache thatdoes not respond to any therapy show promise. The first iscalled radiofrequency trigeminal ablation (gangliorhizolysis). Thisinvolves destroying the branches of the trigeminal nerve thatcarry the pain of cluster. It is done while the patient is awake.A long needle is inserted in the cheek or mouth and is

advanced to an area just outside the brainstem.This treatmentusually works, but it necessitates making the cornea of the eyeon the treatment side permanently numb.This can lead to dis-comfort in that eye as a mild side effect.

The second approach, which is newer and more exciting,involves placing a radiostimulator deep into the brain at thesite of the cluster generator in the hypothalamus. This hasworked in 14 patients treated in Milan, Italy, by Drs. MassimoLeone and Gennaro Bussone.There have been dramatic resultsfrom this procedure, without any complications in their hands.Given the high rate of success with preventive medications,thankfully, few people require consideration for surgery.

Chronic cluster headache is at times more difficult to treat;patients with this condition are the ones who occasionallyneed a surgical approach.

CONCLUSION

There are several effective treatments for the acute care andprevention of cluster headache.We often use them in combi-nation. Only a few severe cases of chronic cluster need to beconsidered for surgical intervention.

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A t The New England Center for Headache, we share thebelief of many clinicians that an appropriate combination ofpharmacologic and nonpharmacologic (without medication)treatments can be more effective than either alone. Nonphar-macologic treatment techniques can be classified as active andpassive.Active techniques require patient involvement, respon-sibility, and participation, focusing on such activities as keepingheadache calendars, making nutritional changes, exercising,practicing relaxation techniques, and modifying behavior thatmay contribute to headache.With passive techniques, patientssimply receive treatments without modifying their behavior.

ACTIVE TECHNIQUES

The underlying concept that patients’ behavior is key to thecontinuation or relief of any illness is the basis of behavioralmedicine. Doctors and patients should review issues that mightstand in the way of successful treatment. Because we recognizehow difficult it can be to make changes in lifestyle, we provideour patients with clear instructions and initiate discussionsabout potential pitfalls.This chapter reviews important activetechniques that may help you deal with your headaches.

Headache CalendarHeadache calendars or diaries are daily logs of anything thatmight relate to your headaches and are vital to appropriatetreatment.As we discuss how to use a headache calendar, referto Figure 12-1.

A headache calendar helps a patient record ongoing infor-mation about the frequency, intensity, and duration ofheadaches. It can also help patients monitor how and when totake medication, track its effectiveness, and document potential

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HEADACHE TRIGGERSHormones

1. Menses2. Ovulation3. Hormone Replacement

Diet4.Alcohol5. Chocolate6.Aged Cheeses7. Monosodium Glutamate (MSG)8.Aspartame (Nutrasweet)9. Caffeine

10. Nuts11. Nitrites, Nitrates12. Other

Changes13.Weather14. Seasons15.Travel (Crossing Time Zones)16.Altitude17. Schedule Changes18. Sleeping Patterns19. Diet20. Skipping Meals

Sensory Stimuli21. Strong Light22. Flickering Lights23. Odors

“Stress” 24. Let-Down Periods25.Times of Intense Activity26. Loss (Death, Separation, Divorce)27. Moving28. Job Loss/Change29. Crisis30. Other

BIOLOGY

Figure 12-1: A, Thefront of the headachecalendar used at ourcenter. B, The back of the calendar.

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B

headache triggers.The calendar helps to show any relationshipbetween headaches and a woman’s menstrual cycle. Each cal-endar represents 1 month of headache activity.

We ask our patients to record headache intensity, timing,medications used, and triggers. Both preventive and acute caremedications must be listed. When listing acute care medica-tions, patients record the degree of relief obtained, rangingfrom 0 for no relief to 3 for complete relief. Under the head-ing Nonmedication, patients record exercise, relaxation activities,and other recommended techniques. Figure 12-1B shows thereverse side of our calendar, which lists potential headachetriggers. Patients record these elements under Triggers on thefront of the calendar.

To record the days of menstrual flow, women enter Xs inthe boxes labeled Periods. Finally, all medications—both pre-scription (from us and from other physicians) and off-the-shelfmedications—must be recorded accurately.

These calendars help doctors monitor their patients’progress.The first calendar is used as a baseline, and at follow-up visits, the doctor reviews any changes in the calendar andrecords them as percent change from the baseline. Patientswho take frequent doses or large quantities of pain relievers orergotamine use the calendars to follow a specific program, thegoal of which is to decrease and eliminate daily use of thesemedications.

Relaxation TechniquesThe goal of relaxation techniques is to reduce the intense“fight or flight” response and also the levels of substances thebody produces in response to stress. Deep rhythmic breathingtechniques are the basis of all relaxation strategies.To try deeprhythmic breathing, sit in a comfortable chair in a quiet envi-ronment; loosen your collar and belt, and close your eyes.Breathe in deeply and slowly, making sure that your abdomenmoves more than your chest. At first, inhale to a count of 3,

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working your way up to 10 as you master the technique.When you reach your peak inhalation, hold it for a second orso and then let it out slowly to the same count. It may behelpful for you to focus on “inhaling relaxation” and “exhalingtension” as you do the exercise.

Progressive re laxat ion. Tense your toes slowly as youinhale to a slow count and then relax them as you exhale.Then move up your body, alternately tensing and relaxing themuscles of your calves, thighs, buttocks, abdomen, back, fin-gers, arms, shoulders, neck, and—finally—the muscles of yourhead and jaw.

Autogenic training. Try repeating a series of phrases toyourself to suggest changes such as feeling warmth and heavi-ness.You might, for example, repeat, “My legs are warm andheavy” while associating this with a pleasant feeling. Move upthe body as described for progressive relaxation.

Visual imagery. Help relax the head and neck muscles byvisualizing them as tight, scrunched, uneven, crooked, andcrossing lines. Then focus on making the lines smoother,straighter, and evenly spaced. Visualize yourself on a sandybeach with your hands under the hot sand. Now feel the sandwarm your hands. Exercises that focus on warmth may helppatients with migraine, many of whom tend to have coldhands and feet. Done successfully, visualization can divertblood flow from the head to the hands and/or feet whilebringing on a state of relaxation (Figure 12-2).

Body scan. Our colleagues Steven Baskin and RandallWeeks at The New England Institute for Behavioral Medicinein Stamford, CT, teach their patients how to perform a “bodyscan.”They suggest that their patients remain alert for signs oftension in the head, neck, shoulders, arms, or legs throughoutthe day.Without realizing it, many people hunch their shoul-

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ders; this creates muscle tension in the shoulders, neck, andhead. Or they may contract muscles around the neck or heador clench their jaws or fists. People who check for these signsof tension throughout the day may be able to reduce muscletension and decrease the effects of stress on the body.This typeof body scan can be accompanied by deep breathing and otherrelaxation techniques. Get in the habit of stopping what youare doing once every hour to check for signs of muscle tensionand to take a quick deep-breathing/relaxation break. Relaxwith gentle neck rolls: allow your chin to fall to your chest,then gently rotate your head right and left 5 or 10 times (Figure 12-3).

If you work at a computer for hours at a time, take a fewminutes every hour or so to cup your hands over your eyes,giving your eyes a chance to rest.

Biofeedback. Biofeedback is commonly used in the treat-ment of both tension-type headache and migraine. It has notbeen found useful in cluster headache. Biofeedback may be

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Figure 12-2: Visual imagery: visualize yourself in a relaxing, beautifulplace.

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administered by a clinical psychologist trained in the tech-nique or by a trained biofeedback technician. More effectivein children but also helpful in adults, the goal is to reduce thesymptoms and, ultimately, to eliminate the need for feedback.

Biofeedback is a “return of information” about biologicprocesses. It works because electronic equipment senses infor-mation such as temperature or muscle tension and gives youauditory or visual feedback over time. The combination offeedback and reinforcement helps you to control muscle ten-sion, hand temperature, and other functions.

Cognitive TherapyCognition means thinking. Many people have negative feelings,and they translate these into such statements as, “I will neverget rid of my headaches.” Cognitive therapists believe that ifyou can change your thoughts, you can change the feelingsassociated with these thoughts. Cognitive therapy has provensuccessful in treating anxiety disorders and depression. It hasalso proven useful in treating headache disorders. Psychologistsand other health care professionals who practice cognitivetherapy can help you challenge these negative thoughts,change your thinking, and, ultimately, change the way you feel.

Figure 12-3: How to do a neck roll: flex your chin to your chest, thengently roll your head to either side 5 to 10 times.

This can give you a more positive, optimistic, and less destruc-tive way to think, feel, and be.

PsychotherapyPsychotherapy alone has not been found useful as a headachetreatment. If, however, headaches are accompanied by psy-chological difficulties, marital problems, job-related difficul-ties, depression, anxiety, and other problems, psychotherapycan help. Group therapy, particularly in the form of supportgroups, has been useful for headache sufferers and patientswith a variety of chronic illnesses. Headache groups areoffered in cities throughout the United States by the AmericanCouncil for Headache Education (ACHE) and the NationalHeadache Foundation (NHF).

Lifestyle ChangesAll of the techniques described in this chapter require you toreview and modify various aspects of your lifestyle. Calendarscan be useful in helping you identify potential headache-provoking or stressful situations and trigger factors, includingfood. Remember to eat a healthful balanced diet at regulartimes each day. Exercise is vital for reducing headache andmaintaining good health (Figure 12-4).

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Figure 12-4: Lifestyle changes: eat healthful foods and exercise regularly to feel good and reduce headaches.

Because many patients focus on others’ needs but leave lit-tle time for themselves, we suggest that our patients use anappointment book to schedule time for themselves—“mytime”—and to keep to the schedule (Figure 12-5).

PASSIVE TECHNIQUES

AcupunctureAcupuncture, an ancient Asian healing art, involves placingneedles in the skin at specific points. Acupuncture correctswhat are termed imbalances between the two parts (yin andyang) of a life force known as ch’i.Applied correctly, the nee-dles cause minimal or no pain or discomfort. If you have noresponse after six to eight sessions, acupuncture probably willnot work for you. Most patients say that acupuncture elimi-nates any pain they are having at the time but that it is not ableto prevent pain in the future.

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Figure 12-5: Use an appointment book or personal digital assistant toschedule “my time” regularly.

AcupressureAcupressure is a technique based on acupuncture. Some havefound using the thumb and forefinger to squeeze the webbetween the thumb and forefinger of the other hand effectivein aborting migraine. For tension-type headache, pressure canbe applied to the small indentations approximately midwaybetween the outer border of the eye and the inner border ofthe ear and also at the back of the head.

Chiropractic TherapyChiropractic therapy is based on the theory that most diseasesof the body are a result of misalignment of the vertebral col-umn. The goal of the treatment is to realign the vertebraethrough the use of manual techniques called adjustment. Manyneurologists question the validity of chiropractic therapy andare concerned that aggressive manipulation, or adjustments, ofthe neck may injure important structures, such as the bloodvessels that supply the brain.

Physical and Occupational TherapiesPhysical therapy has been used in headache disorders and, inparticular, in tension-type headache, in which the neck andshoulder muscles may be involved. Heat and massage havebeen used as muscle relaxants since antiquity, and newer tech-niques, such as ultrasonography, that deliver deep heat to mus-cles have been shown to be helpful in reducing spasm andtenderness.

Some patients get relief by taking a warm shower. Electri-cal stimulation may also be beneficial. Many patients may ben-efit from improvement in posture and gait, and these patientsmay be given appropriate exercises to do at home. Other treat-ments, such as active and passive stretching, increase the rangeof motion about the neck.

Some patients’ occupations contribute to muscle tension.Administrative personnel, telephone representatives, and those

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who use computers may all develop tense muscles in theirbacks and necks and postural problems that contribute to ten-sion-type headache. Frequent breaks and professional atten-tion to posture may help.

Application of cold to the head may help constrict dilatedblood vessels, override pain transmission, numb the skin, andreduce metabolic activity in muscles, contributing to the reliefof pain. Studies have shown, and many of our patients agree,that the “headache ice-pillow” is useful.The molded pillow fitscomfortably at the back of the head and neck and holds afrozen gel pack that ices the neck. Ice applied to the forehead,eyes, and temples can also be helpful.

Massage TherapyMassage can reduce muscle tension in various parts of thebody, and it can reduce headache.A variety of techniques arepracticed by licensed massage therapists.

Trigger Point InjectionsLocated in various parts of the body, trigger points are smallareas that feel like knots of muscle tissue; they are tender totouch and may refer pain to various areas of the head. Theexact cause of trigger points is not fully understood. However,an injection of local anesthetic into these tender points can behelpful.

Transcutaneous Electrical Nerve StimulationTranscutaneous electrical nerve stimulation (TENS) blocks thetransmission of pain with electrodes placed on the skinbetween the pain and the brain.This therapy has proven suc-cessful in treating other types of chronic pain, but, at this time,the results of TENS therapy for headache have been some-what disappointing. A new type of low-intensity stimulationto the ear lobe has been tested but is not widely used. Magnetsalso have been tried, sometimes with beneficial results.

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NATUROPATHY AND HOMEOPATHY

Naturopathy and homeopathy represent alternatives to tradi-tional medical treatments and are attractive to some patientswho want to avoid pharmacologic therapy. Naturopathy usesonly natural physical forces such as air, sunshine, water, andheat. Homeopathy uses natural substances and minute amountsof the active ingredients in some medications. Traditionalphysicians would consider the amounts of these medicationsused to be far too small to produce a therapeutic response andattribute any effects to a placebo response.All the same, somepatients state that they have benefited from these approaches.

HERBAL, MINERAL, AND VITAMIN THERAPIES

Do not use any of the following substances without first check-ing with your doctor.

FeverfewA variety of herbal therapies have been used to preventmigraine, the most popular of which has been feverfew, whichis derived from the chrysanthemum family of plants.A recentlarge review of all of the studies on this herb was inconclusiveas to its benefits. Feverfew is available in several forms anddosages and is usually found in health food stores.

MagnesiumMagnesium is a trace element found in the body. Some sci-entific evidence suggests that magnesium levels are lower inthe brains of migraine patients. Use of magnesium to treatmigraine is under study. We recommend using 400 to 600mg per day of magnesium or chelated magnesium as long asit does not produce diarrhea. The evidence for the effec-tiveness of magnesium in headache prevention seems to bestrongest for menstrually associated migraine and migrainewith aura.

Vitamin TherapiesDr. Jean Schoenen, professor of neurology in Liege, Belgium,has reported that vitamin B2 (riboflavin) fares significantly bet-ter than does placebo in preventing headache when taken in adose of 400 mg per day for 3 to 4 months. He also believesthat riboflavin is more likely to be helpful in people who havemigraine with aura.

Recently, Dr.Todd Rozen, when working at the JeffersonHeadache Clinic in Philadelphia, PA, published an open trialof 150 mg of coenzyme Q10 each day in recurrent migraine,with promising results. Dr. Peter Sandor of Zurich, Switerland,has just completed a double-blind trial showing that 300 mgper day is effective in reducing migraine attacks.

Petasites (or butterbur) was studied by Prof. Richard Lip-ton, and doses of 50 to 75 mg twice daily were helpful in pre-venting migraine.We suggest the brand name Petadolex at adose of 50 mg three times per day.

We sometimes recommend 400 IU of vitamin E daily.High doses of vitamin A are not only potentially toxic, theymay also cause headache. Doses of 150 mg or greater of vita-min B6 can cause harm to peripheral nerves, so we havestopped recommending this therapy. Some claim that vitaminC helps headache; however, the results are inconsistent.

Garlic and GingerGinger clearly reduces nausea for some people and can betaken during pregnancy and for frequent nauseating migraines.Some patients have found that garlic has properties that mightbe useful in migraine.

GinsengGinseng is said to decrease tension and relieve headache. It isavailable as a tea and in capsules, tablets, and dried root pow-der. Ginkgo biloba and valerian root have been touted aseffective by patients.

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GuaranaIn Brazil, guarana is a popular headache remedy (it is evencontained in pop drinks). Guarana contains caffeine.

CoEnzyme Q 10The supplement CoEnzyme Q 10 has recently been shown tobe helpful in the prevention of migraine in two scientific stud-ies.When given every day in a dose of 150 to 300 mg, it worksbetter than placebo in lowering migraine frequency. It maywork by increasing the energy production in the nerve cell.Time will tell if this turns out to be a helpful treatment.

CONCLUSION

A number of treatments alternative to pharmacologic therapyare available. Some of these techniques may be helpful to you,and others may not. Keep in mind, however, that an immediateand permanent cure for migraine has not yet been discovered.

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We feel that an educated patient is a patient who has thepotential to experience optimal headache relief. You shouldknow as much as possible about your headaches, your treat-ment plan, and the medications you take. Sometimes theamount and type of information a patient receives are definedby the doctor-patient relationship. Roter and Hall, in theirbook Doctors Talking with Patients/Patients Talking with Doctors,*describe a number of different types of doctor-patient rela-tionships.We feel that the mutual doctor-patient relationshipyields the most positive treatment outcome.Thus, we urge youto find a physician who is open to this style and who will takethe time to listen to you, hear your concerns, educate you, andgive you feedback about your condition, treatment options,and medications (Figure 13-1).

Your doctor should accept the validity, reality, intensity, andquality of your pain. He or she should do the following:

• Accept your complaints, not dismiss them as unimportant.• Take the time to listen to you.• Understand headache. It is all right to ask if he or she sees

many headache patients and what the success rate is.• Seem compassionate and understanding.• Seem flexible about exploring a variety of treatment

options.• Take the time to discuss findings, diagnosis, and treatment

plan, as well as alternative treatments.• Answer your questions to your satisfaction.• Tell you what to expect from treatment (prognosis).

PATIENT-DOCTOR RELATIONSHIP

CHAPTER 13

*Roter DL, Hall JA. Doctors talking with patients/patients talking with doctors.Westport (CT):Auburn Health; 1992.

• Tell you what medication isbeing prescribed, how itworks, how frequently to takeit and when, and what sideeffects it may cause.Your doc-tor should note significantdrug interactions (includingalcohol) and tell you whichoff-the-shelf medications toavoid. He or she should sayhow long you will need totake the medication, how andwhen to reduce or increasethe dosage, and how or whento discontinue it.

• Describe to you any tests ordered and their purposes andexplain how the results will be used.

• Discuss with you nonpharmacologic interventions relatedto changes in your lifestyle (sleep habits, diet, exercise, andwork conditions). In addition, your doctor should expressinterest in how you plan to make these changes.

It is a good idea to write down all of your questions beforea visit to any doctor.These questions should include how tocontact the doctor when the office is closed and who the con-tact is when your doctor is not on call. Be sure to ask whetheryour doctor has a specific “telephone time” for taking calls;many do.

Remember, taking a cooperative active role in the treatmentof your headache improves your chances of success. Gooddoctor-patient communication is an important beginning.

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Figure 13-1: A good doctor-patient relationship is basedon trust and leads to moreeffective therapy.

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Your treatment plan should include several levels of inter-vention for home care to decrease the likelihood of yourneeding emergency care. Backup or rescue medication may beneeded for occasional headache attacks. If you have to go to anemergency room, go with someone who can take you home;the staff might otherwise be reluctant to give you strong painor antinausea medications, which might sedate you.Althoughsome emergency rooms are set up for headache patients, mostput patients with headache in noisier, colder, brighter roomsthan are ideal.You may have a long wait because the staff willnot consider you as sick as some of the more critically illpatients.With this in mind, we suggest that you take with youa sweatshirt, dark glasses, and patience.

Because emergency room staff may suspect headachepatients of drug-seeking behavior, we provide our patientswith cards that identify them as migraine sufferers, suggestappropriate treatment to the emergency room nurse andphysician, and list our telephone number if the staff wants toverify information with us. In a “headache-friendly emer-gency room,” you can expect to be ushered into a dimly lit,quiet room where you receive a blanket to keep you warmand a basin in case you vomit. The staff will evaluate youappropriately, and if you say you are having pain typical of oneof your migraine attacks, you will probably be treated quickly,with little testing. If, however, you raise any of the red flags (seeChapter 5), you may undergo further evaluation.This can bevery helpful if there is something new going on, but it can berepetitive, costly, and time consuming if you are experiencinga typical severe migraine.

EMERGENCY DEPARTMENT AND HOSPITAL TREATMENT

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MIGRAINE TREATMENT

If you have intermittent migraine and need acute care, you maybe lucky enough to receive injectable dihydroergotamine (DHE45), subcutaneous sumatriptan (Imitrex), or intravenous treat-ments, including steroids, ketorolac (an anti-inflammatory med-ication), and/or valproate (Depacon), which are the bestinjectable medications currently available to stop a migraineattack. Zolmitriptan (Zomig) nasal spray can also be used.Antinausea medications may be administered, and these areexcellent as well. Far less helpful are the opiates. Injections ofmeperidine (pethidine), hydrochloride (Demerol), and promet-hazine hydrochloride (Phenergan) or other antinausea medica-tions are the most common cocktail used in US emergencyrooms, although they are often not that effective in stopping themigraine process or getting the patient functioning.

D.H.E. 45D.H.E. 45 (see Chapter 9) has been available for half a centuryand can be injected intramuscularly, intravenously, or under theskin (subcutaneously). Given alone, D.H.E. 45 gets rid ofheadache for a long time and often reduces nausea.When ourpatients go to the emergency room, we recommend that theyreceive three intramuscular injections: D.H.E. 45, 1 mg; dexam-ethasone (Decadron), a steroid, 4 mg; and promethazine (Phen-ergan), 50 mg for nausea. The anti-inflammatory ketorolac(Toradol), 60 mg, can be substituted for the steroid or D.H.E.45.

SumatriptanSumatriptan (Imitrex) is a 6 mg injection given under the skin(see Chapter 9); it can be self-injected at home to avoid the emer-gency room visit, but it is sometimes given in the emergencyroom as well.More than 80% of people treated with sumatriptanreport significant relief and are usually free of headache after 1hour. If less than 100 mg of sumatriptan has been taken earlier at

home, an injection can be given. If any other triptan has beentaken earlier that day, sumatriptan cannot be given.

Miscellaneous MedicationsAntinausea medications. Prochlorperazine (Compazine), 10mg given intravenously, is effective in stopping a migraine and con-trolling nausea.Twenty-five to 50 mg can be given intravenouslyover 10 minutes and may help knock out a headache.Sometimes itcauses tightening of the muscles as a side effect, which usuallyresponds to a small intravenous dose of diphenhydramine(Benadryl). Metoclopramide (Reglan), 10 mg given intravenously,can block nausea and headache, often without sedation. It can alsocause tightening of muscles and, occasionally, some irritability.Other related medications given intravenously include droperidol(Anapsine).Recently,droperidol has been associated with significantcardiac problems so that cardiac monitoring and electrocardiogramsare required when it is administered.Chlorpromazine (Thorazine),which is in the same group of medications, can be given eitherintravenously or by rectal suppository and tends to make patientssleepy and/or lower their blood pressure.When given intravenously,it is often preceded by intravenous fluids to prevent the lowering ofblood pressure. Finally, ondansetron (Zofran) and granisetron(Kytril) given intravenously stop nausea rapidly and do not causedrowsiness or other side effects. (See Chapter 9 for more details.)

Valproate. Intravenous valproate sodium (Depacon), anantiepilepsy medication, and the injectable form of divalproexsodium (Depakote), used for epilepsy, migraine, and psychiatricproblems (see Chapter 10), appear to be useful in stoppingmigraine pain rapidly. Depacon appears to have fewer sideeffects when given intravenously than when taken orally.

Opiates. Rarely do we prescribe opiates (narcotics), bothbecause they usually do not work well to stop migraine andbecause they can cause dependency.These powerful painkillerscan be tried if all else fails, if the patient has already taken a trip-

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tan or an ergot, or if the patient has vascular disease and cannottake medication that affects blood vessels (see Chapter 9).Injectable opiates such as meperidine (Demerol) or morphineshould be used no more than once per month and tablet formsno more than one day per week. Some emergency rooms havetaken meperidine out of the pharmacy because it can causemany side effects, including making people irritable or drowsy,and the beneficial effect often does not last very long.An opiateis often given with an antinausea agent such as promethazine(Phenergan) or a combined antinausea agent/antihistamine,hydroxyzine (Vistaril). Butorphanol (Stadol) can be given byinjection or nasal spray. It rapidly relieves pain,may cause drowsi-ness or dizziness, and does not usually produce euphoria (a“high”). It is probably the most habit forming of all of the nar-cotics. It can be helpful when used occasionally in small doses.When not used properly, it causes side effects and dependency.

ConclusionAt-home medication is better than emergency room medica-tion. If you can avoid going to the emergency room for treat-ment by having medication that is powerful enough for hometreatment, you will be better off. This almost always meansusing a triptan, sometimes with a rescue or backup medication.

CLUSTER HEADACHE TREATMENT

If you must go to the emergency room during an attack ofcluster headache, chances are that the attack will be breakingby the time you get treatment. Oxygen inhalation is the mosteffective and safest treatment. Patients who receive oxygenshould be seated, bending slightly forward; the oxygen maskshould fit loosely over the nose and mouth and should deliver7 to 10 L per minute.

Ergotamine tartrate by mouth can be helpful, but D.H.E. 45by injection works faster. Sumatriptan (Imitrex) injection usu-

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ally aborts a cluster attack within 5 to 10 minutes. Zolmitriptannasal spray can stop a cluster headache attack quickly. Painmedication is not specific for cluster headache, but it maydecrease the intensity of the pain if nothing else has worked.Cluster patients should not use opiates (narcotics). See Chapter11 for a detailed discussion of cluster headache treatment.

SPECIALIZED INPATIENT THERAPY

When headaches occur daily,are severe and incapacitating,and areassociated with disability,decreased quality of life,or rebound syn-dromes from analgesic and/or ergotamine or triptan overuse,aggressive therapy with intravenous medication and cautiouswithdrawal of the offending medications must begin.

Although treatment can be attempted on an outpatientbasis, many patients with severe withdrawal symptoms must behospitalized, and a well-staffed, properly designed, interdisci-plinary hospital program directed by headache specialists mayyield marked improvement and long-lasting benefits. Patientswho take butalbital-containing medications, ergots, tranquiliz-ers, or opiates every day are usually best detoxified in a hospi-tal setting to ensure that serious withdrawal symptoms such asepileptic seizures, tremors, insomnia, anxiety, diarrhea, andincapacitating rebound pain do not occur; if they do occur,appropriate medical support is available.

CONCLUSION

Several levels of migraine treatment should be provided topatients in an attempt to avoid trips to the emergency depart-ment. Although we agree that it is preferable to treat patientsappropriately on an outpatient basis, our experience has shownus that this is not always possible.Thus, we are convinced thatunder certain circumstances, inpatient headache treatment isappropriate and necessary and, ultimately, cost effective.

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Children are not immune to headache; the youngest patientto visit our center was only 3 years old when she first came tosee us. Her mother reported that the child seemed to experi-ence severe headaches since the age of 6 months. Three orfour times per year, the little girl would become distraught,vomit, and cry inconsolably.The mother related that the childpressed the same side of her head to her mother’s chest eachtime she had an attack (Figure 15-1).All medical examinationsand tests were completely within normal limits. Betweenepisodes, the child was happy and content.

When the child was old enough to describe her pain, itbecame clear that she was experiencing headache. Headachesare less common in children than in adults. Studies show that39% of 6 year olds get occasional headaches, as do 70% of 15year olds and 90% of adults.Approximately the same numberof boys get headaches as do girls. Migraine occurs slightlymore often in 8- to 11-year-old boys than in girls of the sameage range. From puberty on, migraine occurs three times moreoften in girls and women than in boys and men.

DESCRIPTION OF HEADACHE TYPES

The majority of headaches in children are migraine and/or ten-sion-type headaches rather than headaches owing to a seriousunderlying medical problem. Migraine in children tends tooccur more frequently on both sides of the head than on oneside, and attacks are usually shorter than are those in adults,sometimes lasting for only 1 to 2 hours.The headaches may notthrob but, rather, are steady and squeezing or pressure-typeheadaches. Children’s attacks can come on rapidly and becomeintense in a short period of time. A child suffering fromheadache almost always appears pale and ill and may complain

HEADACHE IN CHILDREN

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of nausea and then vomit.A child may also exhibit a strong urgeto sleep.Although sleep brings migraine relief throughout life, itseems to be especially effective for children, who can awakenafter 1 or 2 hours and go out to play feeling absolutely fine.

Children often describe tension-type headache as a mildheadache on both sides of the head or as a steady, nonthrob-bing, squeezing, pressing, or aching in the forehead or at thetop of the head. Headaches such as these should not causeconcern; they usually respond to relaxation techniques, bio-feedback training, altered diet, or small amounts of off-the-shelf medication. We recommend, however, that children

Figure 15-1: A small child with an occasional severeheadache presses his head to his mother’s chest.

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under the age of 15 years avoid using acetylsalicylic acid (ASA)because it has been associated with Reye’s syndrome. Of off-the-shelf medication, we recommend anti-inflammatory med-icines such as ibuprofen (Advil or Motrin), naproxen sodium(Aleve), or ketoprofen (Orudis KT). Acetaminophen (such asin Tylenol) can also be helpful. Of prescription medicine, weprefer Midrin, which contains a mild blood vessel constrictorcalled isometheptene.We prefer not to use butalbital-contain-ing medication such as Fiorinal or any of the opiates. Childrenmay develop daily chronic tension-type headache, which canbe very difficult to treat.The overuse of pain medication canlead to analgesic rebound headaches in patients, worsening theproblem and making it harder to treat.

WHEN TO WORRY

Although most headaches in children are not serious, parentsshould watch for the following danger symptoms and signs,which should prompt them to seek medical attention promptly:

• Headache with fever. This may be due to an infection,which could involve the brain or sinuses.

• Stiff neck and vomiting, with or without fever.This may becaused by meningitis (an inflammation of the covering ofthe brain and spinal cord) and requires immediate medicalattention.

• Fever, confusion, and drowsiness. Immediate medical atten-tion is needed to rule out a viral infection of the brain(encephalitis). It is uncommon, but it does occur.

• Fever, bull’s-eye rash, history of a tick bite, joint pains, backpain, and weakness on one side of the face or in one armor leg. These symptoms can indicate Lyme disease andshould be evaluated immediately because Lyme disease canbe cured if treated early.

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• Slowly progressive headache. If a child has a headachethat steadily worsens over a period of days or weeks, espe-cially if the headache is present early in the morning andis associated with drowsiness, visual complaints, weakness,numbness, incoordination or speech problems, nausea, orvomiting, the child should be evaluated immediately.Although it is unlikely for a child to develop a brain tumoror blood clot, it must be ruled out if these symptoms arepresent.

• Headaches brought on by exertion. Some children com-plain that they get headaches when they participate inphysical exercise.This is usually a benign (not serious) exer-tional headache or migraine triggered by exercise. Onlyrarely is this caused by a neurologic problem, but it shouldbe evaluated.

• After head trauma (injury), most children develop briefheadaches that disappear within 1 to 2 days. If the head-aches are intense and associated with nausea, vomiting,drowsiness, or any other neurologic symptoms, the childshould be seen by a doctor immediately.

EVALUATION

Although medical conditions may play a role in childhoodheadache, they do not commonly cause recurrent headaches.See Chapter 6 for information about appropriate examina-tions and testing. Children should be told what to expect fromdiagnostic tests; this helps to reduce anxiety and encouragesthem to cooperate.

“MIGRAINE EQUIVALENTS”

Unexplained symptoms that some consider migraine relatedmay be more common in children than in adults. Some chil-dren experience unexplained episodes of abdominal pain asso-

ciated with nausea and vomiting but no headache. Some doc-tors believe that these episodes may be caused by the samebrain mechanisms that cause migraine and term these painsabdominal migraine. Other migraine equivalents may includecyclic vomiting, in which children vomit profusely from timeto time but for which no cause can be found. Finally, we notethat our adult migraine patients are much more likely to havehad motion sickness and car sickness as children than peoplewho do not suffer from migraine.

PSYCHOLOGICAL FACTORS

Although psychological factors are not a major cause ofheadache in most children, they do contribute in some cases. Ifheadaches are chronic or do not respond to the usual treat-ments, it is appropriate to evaluate the role of stress and socialand psychological factors. Children often express their reactionto family conflict through physical complaints. If they arealready prone to migraine, they may complain of an increasedfrequency of headaches. A small percentage of adolescentsexperience chronic daily headache. Some studies have shownthat adolescents with chronic daily headache who do notrespond well to treatment show evidence of depression, whichmust be treated. A few children have chronic daily headachethat responds neither to headache therapy nor to psychother-apy.Although this pattern is not yet well understood and is dif-ficult to treat, most “outgrow” their chronic headache by thetime they complete high school or college.Anxiety may play arole in some children’s headaches, and our goal is to make thechildren’s lives as normal as possible. The majority of thesechildren become disabled and must be tutored at home whentheir condition becomes severe.Therefore, we ask school offi-cials for flexible programming and to make arrangements for arest area for timeout as needed, along with any other measuresto keep them in school for as many hours as possible. Some

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school systems are much more cooperative than others, andthe patients reap the benefits.

Families and doctors should cooperate with school officialsto help them realize that these children suffer from a neurobi-ologically based disorder and need understanding and psycho-logical and medical help if they are to overcome it.

TREATMENT

Pharmacologic TreatmentWith some exceptions, the medications used to treatheadaches in children are similar to those given to adults.Wetend to use an absolute minimum amount of medication—justenough, no more—and rely as much as possible on nonphar-macologic interventions.As with adults, pharmacologic treat-ments fall into three categories: symptomatic, specific (acutecare), and preventive.

Symptomatic therapy. These measures address the pain andnausea and may include off-the-shelf medication, in appropri-ate dosages and frequency. Children, too, can develop reboundheadache and should not take medication on a daily basis forextended periods.

Because of the risk of Reye’s syndrome, we recommendthat acetaminophen (Tylenol), ibuprofen (Advil, Nuprin,Motrin), naproxen sodium (Aleve), or ketoprofen (Orudis KT)be used instead of ASA. For more severe headaches, Tylenolwith codeine may be used safely on an occasional basis.Anti-nausea medication should be used as appropriate in smalldoses.We favor promethazine (Phenergan) 12.5 or 25 mg bymouth for those who are not vomiting and by suppository forthose who are vomiting. Emetrol is an effective off-the-shelfliquid antinausea medicine with no side effects.

Specif ic acute care agents. No specific medication formigraine is approved by the FDA for children, although

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ibuprofen, which often works, is approved for children forgeneral use. When prescription medications are needed forchildren over the age of 6 years, our first recommendation isfor a combination of isometheptene, dichloralphenazone, andacetaminophen (Midrin), which can be given with or withoutantinausea medication. Children tolerate this combinationwell, and the capsule contents can be mixed into a tablespoonof applesauce for those who cannot swallow capsules.The doseis one capsule at the start of a headache; this may be repeatedin 1 hour if the headache persists.When stronger medicationsare needed, we sometimes (but rarely) prescribe butalbital,acetaminophen, and caffeine (Fioricet or Esgic) or the samewithout caffeine (Phrenilin).The dose is one tablet at the startof a headache.We prefer to work in cooperation with pedia-tricians and family doctors to determine what might be bestfor a given child.

When prescription nonsteroidal anti-inflammatory agentsare appropriate,we often prescribe ibuprofen, naproxen sodium(Anaprox, available off the shelf as Aleve), or meclofenamate(Meclomen). In more severe cases and on rare occasions inchildren who are 10 years or older, we sometimes prescribesmall doses of ergotamine if we do not want to use a triptan.

When migraine is persistent and unresponsive to treat-ment, some headache specialists give small doses of dihydroer-gotamine (DHE 45) intravenously or by injection to break thecycle. Sumatriptan (Imitrex) 20 mg nasal spray has been foundto be safe and effective in adolescent migraine, and US Foodand Drug Administration (FDA) approval is expected for usein adolescents down to age 12 years.

Although not yet approved by the FDA for use by thoseunder the age of 18 years, all of the available triptans are pre-scribed in small doses for children on a regular basis by pedi-atric neurologists and headache specialists. Evidence is best forsumatriptan (Imitrex) nasal spray, which has been proven effec-

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tive and safe for use in adolescents, and, although not approvedby the FDA, has been approved by the European Union forprescription to adolescents.There is also evidence of effective-ness for zolmitriptan (Zomig) nasal spray in teens withmigraine, and we prescribe either for our adolescent patientsoff label when they need a triptan.Triptan tablets are not asclearly effective, because pediatric migraine is often short-lived, and is often associated with vomiting, both of whichexplain the usefulness of nasal spray formulations.

Prevent ive medicat ion. When children have frequent,severe headaches that interfere with their lives, one of our firstlines of defense is cyproheptadine (Periactin), an antihistamineavailable in both liquid and tablet forms, given at bedtime.Thedosage is 2 to 12 mg daily.The majority of children respondwell to this regimen, which we decrease or discontinue after 3to 6 months of successful treatment.We generally reserve useof the tricyclic antidepressants (nortriptyline [Pamelor],amitriptyline [Elavil], doxepin [Sinequan],or imipramine[Tofranil]) for adolescents, and we prescribe them only in smalldoses. b-Blockers such as propranolol (Inderal), nadolol (Cor-gard), and atenolol (Tenormin) may be effective, as may anti-seizure medications such as gabapentin (Neurontin). Recently,we have found that topiramate (Topamax) is very effective forchildren and does not cause many side effects, but it must bemonitored carefully. It is not yet approved for migraine treat-ment but is approved for epilepsy, even for 2 year olds. Wesometimes prescribe divalproex sodium (Depakote; Epival inCanada) for adolescent boys but not for younger children, toavoid liver problems, and preferably not for girls past menarche,due to its potential for ovarian problems and birth defects.Wehave seen excellent results with topiramate or zonisamide inadolescent migraine prevention, but teens are particularly sus-ceptible to the side effect of not sweating, which can endangerthem during vigorous exercise during hot summers and which

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must be watched for. Most children with migraine have fewerattacks during the summer, perhaps because their schedules aremore flexible without the pressures of school, and their pre-ventive medication can be discontinued.

Nonpharmacologic InterventionsWe try as much as possible to treat headache, especially in chil-dren, with nondrug alternatives. Chapter 12,“Treatment with-out Medication,” reviews many of these techniques. Inchildren, as in adults, we evaluate the role of diet, daily exer-cise, appropriate rest, and regulation of the sleep-wake cycle;we also look for potential trigger factors. Children who are oldenough should maintain their own headache calendars torecord their headache frequency and intensities, medicationuse, and triggers.We try to avoid having the calendars viewedas more “homework” and encourage parents to let their chil-dren keep their own calendars. Parents should not focus onone type of trigger or another because undue emphasis, forexample, on dietary triggers, may cue some children tobecome “dietary cripples.” Children respond very well tobiofeedback and seem to enjoy working with the biofeedbackcomputers and caregivers.When we notice clear-cut psycho-logical issues or unhealthy family situations, we refer patientsand their families for appropriate therapy, but we continue tofocus our efforts on the biologic aspects of headache disorders.Children’s headaches are not imagined any more than areadults’ headaches.

CONCLUSION

Many children experience headache, and most of theseheadaches are not signs of serious disease. In most cases, acombination of pharmacologic and nonpharmacologic treat-ments helps to relieve headache while enhancing children’squality of life.

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Migraine is three times more common in women than inmen, which is why we have devoted a chapter specifically towomen and migraine.Prior to puberty,migraine occurs slightlymore frequently in boys than in girls, but after menarche (agirl’s first period), its prevalence among women increases dra-matically, suggesting that it may be related to fluctuating femalehormones, specifically estrogen. Women’s susceptibility tomigraine increases at the stages in life outlined in Table 16-1.

The menstrual cycle represents a finely tuned balancebetween hormones produced by the brain’s pituitary glandand the hypothalamus and those released by the ovaries.Theuterus itself produces hormones called prostaglandins, whichcan cause premenstrual cramps, painful menstruation, andheadache. Marked by a rise in estrogen and progesterone lev-els, ovulation (when eggs are released from the ovaries) occursat midcycle, usually between the eleventh and fourteenth daysof the cycle. Hormone levels begin to rise after midcycle andthen fall before menses, as shown in Figure 16-1.

When progesterone levels fall, the lining of the uterus shedsand bleeding—menses—occurs. The first day of bleeding isconsidered day 1 of the cycle.

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HORMONES AND HEADACHE IN WOMEN

CHAPTER 16

Table 16-1: Times at which Women’s Susceptibility to Migraine Increases

Menarche (onset of periods)Start of each menstrual cycleUse of oral contraceptivesEarly pregnancyPostpartum periodPerimenopause (time entering menopause)Postmenopause (time after menopause)Use of hormone replacement therapy such as estrogen and progesterone

MENARCHE

Girls become more susceptible to migraine after they havetheir first menstrual period; one-third of all women withmigraine experience their first attack within the year aftertheir first period. It appears that the normal cycle of hor-mones, especially falling estrogen levels, affects brain, nerve,and blood vessel mechanisms involved in producing migraine.

MENSTRUAL MIGRAINE

As noted in Chapter 3, menstrual migraine is defined as thatoccurring only between 2 days before a period and 3 daysafter it starts. Headaches that occur then and also at othertimes are often called menstrually related migraine. Others definemenstrual migraine more loosely as any headache that occursat predictable times during the menstrual cycle. Sixty percentof women with migraine have more headaches just before orduring their periods.These headaches can be the longest last-ing and worst attacks of the month and can be the most diffi-cult to treat. Some women report an increase in headache atmidcycle when they ovulate (day 13 or 14).

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Figure 16-1: The monthly female hormonal cycle (variations of hormonelevels during the month).

0 14 30Days of the Month

Plas

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Con

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ratio

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mon

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ary

units

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Estrogen

Progesterone

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Occasionally in the past, some of our patients have success-fully used estradiol-17 (Estrace)—a synthetic estrogen—whichis placed under the tongue (sublingually) when a migraineoccurs during a period. The estradiol may stop the attack,reduce its intensity, or make it more responsive to the usualmedications. However, the strategy does not always work, andtriptans stop menstrual migraines more reliably and rapidlyand have, for the most part, replaced this treatment.

Menstrual Migraine TreatmentTreatment of menstrual migraine involves previously discussedpharmacologic and nonpharmacologic interventions. Theseheadaches differ from other migraines only in their timing inrelation to the menstrual cycle and in that they are triggeredby falling estrogen levels just before menstruation.They maylast longer than migraines at other times in the cycle, be moresevere, and be more difficult to treat. For women whoseheadaches occur mostly around the time of menses, we pre-scribe daily preventive medications, but only for those daysleading up to, or during, the projected headache period ratherthan throughout the entire month. This approach is calledshort-term prevention, pulsed therapy, or miniprevention. Refer toChapter 10 for a description of preventive medications. Werecommend that patients start preventive medication 2 to 3days before the expected menstrual headache or 5 days beforethe expected period and continue the medication until men-strual flow stops. The nonsteroidal anti-inflammatory drugs,such as naproxen sodium (Anaprox or Aleve), meclofenamate(Meclomen), flurbiprofen (Ansaid), ketoprofen (Orudis), andibuprofen (Motrin, Nuprin,Advil, and Medipren), have provenespecially useful and should be taken two to three times perday with meals. Some patients respond well to once-a-daydosing with the new cyclo-oxygenase 2 inhibitor anti-inflam-matory medication celecoxib (Celebrex), 200 mg, which maycause fewer gastrointestinal side effects. Sometimes we pre-

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scribe other preventive medications such as the antihistaminecyproheptadine (Periactin), b-blockers, antidepressants, cal-cium channel blockers, and methylergonovine (Methergine).Daily use of bromocriptine (Parlodel) has been prescribed toincrease brain levels of the chemical dopamine, but we havefound it difficult to use and not very beneficial.

Dr. Larry Newman, director of the St. Luke’s-RooseveltHeadache Clinic and clinical associate professor of neurologyat the Albert Einstein College of Medicine in New York, stud-ied the use of sumatriptan (Imitrex). He found that sumatrip-tan 25 mg taken three times a day beginning 2 days before theexpected onset of menstrual migraine and maintained for 5days was effective in preventing the attacks. He and his col-leagues then published a large scientific study that showed thatnaratriptan (Amerge) 1 mg twice daily used in the same wayalso prevented or significantly reduced the frequency of themenstrual migraines. Studies on frovatriptan 2.5 mg twicedaily beginning 2 days before the menstrual migraineheadache and used for 5 days also showed this medication tobe highly effective.A loading dose of 10 mg was given 3 daysbefore flow as a “kick-start” to the short-term prevention.Zolmitriptan used at the same dose in the same way, but with-out the loading dose, also worked.

Hormonal manipulation may be helpful because migraine isoften induced by falling estrogen levels prior to menses. Boost-ing estrogen levels with small doses starting 5 days beforemenses may prevent or decrease the severity of attacks.We pre-fer the use of an estrogen skin patch (Estroderm 0.5 mg) to thetablets. Small doses of estrogen given for this purpose generallydo not affect periods.Other, stronger agents can totally suppressmenses and help headache, but this more powerful treatment isusually reserved for women who are significantly disabled for aweek each month from migraine associated with menses.However, a study by Dr.Ann MacGregor of the City of Lon-

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don Migraine Clinic found that while estradiol skin patchessuppressed migraine while they were on the skin, the migrainesoccurred at an even worse severity when the patches wereremoved. This raises the question whether the hormone wasjust delaying the migraine. This has cut down on our use ofestrogen for short-term prevention.

Progesterone should probably not be given for headachecontrol because it can worsen headache. When given alongwith estrogen to postmenopausal women, instead of beingprescribed in high doses (10 mg) for 10 days, it should bestarted in low doses (2.5 mg) daily. Injections of long-actingprogesterone (Depo-Provera) should be avoided because theymay increase headache and will do so for a full 3 months untilthe progesterone wears off. It is a good idea to have the doctorwho treats your headaches consult with your gynecologist ifhormonal strategies are contemplated.

Migraine attacks should be treated with standard therapiesto abort migraine or lessen the pain (as described in Chapter9).The focus should be on the triptans, which work faster andmore completely than the ergots, but ergotamine with caffeine(Cafergot) or dihydroergotamine (D.H.E. 45, Migranal) can betried if the triptans fail. Migraine attacks in women who takeoral contraceptives (“the pill”) generally occur during estrogenwithdrawal, just prior to or at the start of menses. Sometimesthe pill needs to be stopped if headache becomes more severeor frequent or is associated with neurologic symptoms such asweakness or numbness on one side.There is no evidence in theliterature that hysterectomy is a reasonable treatment for men-strual migraine. In fact, it often worsens headache.

ORAL CONTRACEPTIVE USE

The effect of oral contraceptives on migraine is controversial.We believe that if migraine increases in frequency or becomes

more severe when a woman takes oral contraceptives, then it iswise to discontinue their use. If the migraine is stable in apatient who already takes oral contraceptives, we do not sug-gest that they be discontinued. Patients who experiencemigraine with aura have a slightly increased chance of havinga stroke than do women without migraine.Women who havemigraine with long visual auras (greater than an hour inlength) or auras with weakness, double vision, fainting, andvertigo (hemiplegic and basilar migraines) should not take oralcontraceptives because of a possible greater increase in the riskof stroke. Smoking, of course, is associated with a much moresignificant risk of stroke than are oral contraceptives. Smokersface a risk of stroke 10 times that associated with migraine andoral contraceptives. So, if you smoke and have migraine, par-ticularly migraine with aura, ask your doctor about the use ofthe pill, and stop smoking now!

When oral contraceptives are implicated in migraine,women who discontinue them may not notice improvementfor 6 to 12 months. Each woman must decide for herselfwhether a potential improvement in migraine is counterbal-anced by the risk of pregnancy or a return of gynecologicsymptoms that oral contraceptives were prescribed to relieve.

If avoiding pregnancy is an issue, other forms of contracep-tion can be considered.

MIGRAINE AND PREGNANCY

As many as 75% of women experience a decrease in the fre-quency of their migraine attacks during the last 6 months ofpregnancy. Our experience suggests that migraine withoutaura (the most common type of migraine) is more likely todecrease during pregnancy than is migraine with aura and thatwomen with menstrual migraine are more likely to show adecrease in headache during pregnancy than are those withouta clear menstrual association.The frequency of headaches may

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decrease as pregnancy progresses and estrogen levels stabilize ata high level. Many women get an increase in headaches duringthe first 3 months of pregnancy, sometimes before they evenknow they are pregnant. This can be a problem if they takemedications that should not be taken during pregnancy.

We take a conservative position regarding the use of med-ication during pregnancy; we advise our patients to discontinueall medication prior to attempting to get pregnant. Preventivemedications should be discontinued 2 to 4 weeks beforeattempting to conceive. Because medications that stop migraineacutely (such as the triptans or ergots) should not be used dur-ing pregnancy, the only safe time to use them if a patient isplanning to conceive is during the first 10 days of the cycle aftera true period. Medications that contain ergotamine (Cafergot)may cause uterine contraction and terminate a pregnancy. Insuf-ficient information is available about the effect of the triptanson the uterus or the fetus to justify their use in pregnancy.

We prefer that patients do not smoke and use no caffeine,alcohol, or any medication during pregnancy, including any ofthe standard nonprescription off-the-shelf medications. How-ever, when medication must be used during pregnancy, weurge our patients to fully discuss possible ramifications withtheir obstetrician and pediatrician. If medication is necessary,we recommend acetaminophen (Tylenol) over acetylsalicylicacid (ASA), particularly during the first 3 months. If a morepotent medication is required, opiates may be permitted forsevere pain.When severe and protracted vomiting occurs, wesuggest the use of an antinausea medication such as metoclo-pramide (Reglan) or ondansetron (Zofran). Steroids (dexam-ethasone or prednisone) can be prescribed for severe headache.If attacks occur frequently and preventive medication isabsolutely necessary, cyproheptadine (Periactin) has been ratedby the US Food and Drug Administration as Category B foruse in pregnancy—“no evidence of risk in humans.” Unfortu-

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nately, it may not be thathelpful. Some calciumchannel blockers, b-blockers, and antidepres-sants can be used withcaution. As with anyother medications, use ofpreventive agents mustbe discussed thoroughlywith your physician(Figure 16-2).

POSTPARTUM PERIOD

After delivery, migraine may return with a vengeance, andquickly; in some women, it may occur for the first time afterdelivery. Migraine and menstrual periods tend to be delayed inbreast-feeding women because estrogen levels remain high aslong as nursing continues.We prefer to avoid the use of med-ication in women who are breast-feeding. Recently, the Amer-ican Pediatric Association declared sumatriptan safe duringbreast-feeding, which is a tremendous relief for new motherswith migraine. See Table 16-2 for medications that should notbe used when breast-feeding.

PERIMENOPAUSAL PERIOD

As women approach menopause, they may begin to noticesubtle changes in the frequency, timing, duration, and amountof flow of their menstrual bleeding. Many women with preex-isting migraine may notice that they get more headaches, per-haps owing to fluctuating levels of estrogen and progesterone(Figure 16-3). A small percentage of women may get theirfirst migraines at this time—whether menopause occurs natu-rally or because of removal of the ovaries. If you are approach-

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Figure 16-2: During pregnancy it isimportant to discuss use of any medications with your doctor.

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ing menopause, be sure to mention your migraine history toyour doctor; it may influence whether hormone replacementtherapy (HRT) is implemented.A large controversy has devel-oped over the benefits and risks of HRT.The Women’s HealthInitiative investigators reported in a major study in 2002 thatcombined HRT appeared to raise the risk of heart attack andstroke rather than lower it.The reasons for use of HRT have

been reduced to control ofhot flash–type symptomsand to treat osteoporosis. IfHRT is necessary, it shouldbe given on a continuousbasis rather than cyclically.If progesterone must beused (it helps to preventcancer of the uterus if youhave not had a hysterec-tomy), a low daily dose ispreferable to a high dosetaken 10 days per month.If you notice that you getmore frequent migraineafter starting estrogenreplacement therapy, youmay find that a different

Table 16-2: Medications Not To Be Used during Breast-feeding

Generic Name Brand NameErgotamine tartrate CafergotLithium LithotabsAmphetamine DexedrineChlorpromazine ThorazineAcetylsalicylic acid (ASA) AspirinPhenobarbital —Cyproheptadine Periactin

Figure 16-3: Headache during theperimenopausal period may be dueto fluctuating levels of estrogen andprogesterone.

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estrogen preparation, especially one with a lower dose of estro-gen, causes fewer headaches. We recommend nonpharmaco-logic techniques of headache treatment during menopause(especially considering the new information about HRT), aswell as vitamin supplements such as 400 IU of vitamin E.

Recent studies have shown that the use of 400 mg ofchelated magnesium may be beneficial. We also suggest theuse of 400 mg of vitamin B2 (riboflavin) (see Chapter 12).Many off-the-shelf products are available that may decreasesymptoms of low estrogen.Women have reported benefit fromuse of evening primrose oil, Vitex (chasteberry), and blackcohosh, among other natural remedies, but their true effec-tiveness and long-term safety have not been established.

CONCLUSION

Because women are more susceptible to migraine than aremen, their unique needs require special consideration whenmigraine treatment plans are implemented. All hormonalissues need to be taken into account—menarche, menses, ovu-lation, pregnancy, and menopause.An interested physician willplay a critical role in weaving these hormonal aspects intoyour care.

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A lthough holidays are usually associated with goodtimes, family reunions, and happy memories, they some-times bring loneliness, depression, anxiety, and overcom-mitment—all of which can result in headache in those withthe biologic vulnerability. Headache sufferers may also havemore headaches when they travel, especially to high alti-tudes or damp rainy areas.

HOLIDAY HEADACHES

At The New England Center for Headache in Stamford, CT,we often receive up to three times more telephone calls duringthe holiday season between Thanksgiving and New Year’s Daythan at other times of the year.We attribute this to the com-bined effects of stress factors and the greater exposure toheadache triggers such as certain foods, partying in poorlyventilated and smoke-filled rooms, lack of sleep, and overcom-mitment (Figure 17-1).

Migraine patients are more affected than are others bychanges in daily events and body rhythms, and the holidaysmagnify this susceptibility. The following suggestions shouldbe followed to avoid holiday headaches:

• Allow an unwinding period after your final day at workand before travel and celebration.

• Pace yourself realistically; try not to overextend yourself.Make a schedule that allows you to accomplish a reason-able number of tasks. Do not set unattainable goals.

• Be aware of signs of tension, such as clenched teeth, tenseshoulders, and shallow breathing. When you note them,

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allow yourself a few moments to relax those muscles andtake slow, deep, easy abdominal breaths.

• Try to sleep the same number of hours every night; trygoing to bed at a set time and waking up at the same time.Set specific meal times; do not skip meals or even delaythem. Exercise regularly most days of the week.

• Remember to take medications as prescribed; do notchange dose times. Do not use more than the recom-mended amounts of off-the-shelf or prescription painmedications.

• Take time to unwind after traveling or holiday activities;ease into your regular routine.

Figure 17-1: Holiday headaches are attributed to stress and exposure to such triggers as food, alcohol, parties, lack of sleep, and overcommitment.

HANGOVER HEADACHE

The hangover headache is a familiar holiday phenomenon thatis easier to avoid than to treat. Some tips on prevention follow:

• Drink very little alcohol and drink slowly, over a period ofhours.

• The lighter-color alcohols such as gin, vodka, and whitewine tend to have fewer congeners (impurities) and areless likely to cause hangover headache.

• Use sugar-free mixes to dilute the alcohol and make sureyou drink sufficient nonalcoholic liquids.

• Drink one large 12 ounce glass of plain water for everyhour during which you consume alcohol.

• Before drinking, eat high-protein, more slowly absorbedfoods, such as milk or mild cheese.

• High-fructose food such as apples, honey, grapes, tomatoes,and their juices may help you break down (metabolize) thealcohol faster.

• Stay in a well-ventilated room or go outdoors at intervalsfor fresh air; avoid inhaling cigarette smoke, which lowersthe oxygen content of your blood and starves your brainfor oxygen.

• Eat bland snacks, avoiding salt and foods that trigger yourheadaches.

• Go to bed at a reasonable hour and do not oversleep thenext day.

• At bedtime, take one or two tablets of acetylsalicylic acid(ASA) or off-the-shelf nonsteroidal anti-inflammatorydrugs (NSAIDs) and drink as much water as possible. Putcold compresses over your forehead, eyes, temples, and/orthe nape of your neck.

• Do not drink alcohol the next morning no matter howbad you feel.

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AIR TRAVEL AND HEADACHE

Anxiety over or the stress of travel can trigger tension-typeheadache and migraine, as can cramped airplane seating con-ditions (Figure 17-2). Business- and first-class seating is gener-ally more comfortable than is coach-class seating and may beless likely to trigger a headache.

Headache may also occur because recirculated dry air withdecreased oxygen content (or even cigarette smoke on some in-ternational flights) can stress your respiratory system,your brain,and your body’s ability to regulate its temperature.Airplane cab-ins are pressurized to about 7,500 feet above sea level.This changeaffects many migraine sufferers; however, it affects clusterheadache patients even more readily,and flying may well producea cluster attack, which is difficult to treat on a plane.Travelingthrough time zones, especially toward the east,may cause jet lag;this, in turn,may bring on headaches for those who are sensitiveto disruptions in their daily schedules of meals, sleep time, andwaking time.

141

Figure 17-2 Travel hassles can trigger headache.

The time to start avoiding a travel headache is 24 hoursbefore your flight! Leave plenty of time for all of your activities,such as packing, getting to the airport, and checking in. If pos-sible, check your bags and get your boarding pass at curbsidecheck-in; this helps avoid muscle strain in your arms and neckowing to carrying baggage any farther than necessary, movingyour luggage frequently, and waiting in long lines.Try to get anaisle seat so that you can get up and walk every 45 minutes orso.Move around while you wait for your flight; take little walksin the boarding area.While in flight, do gentle neck exercises(as described on page 106) about once an hour.

If you are flying to Europe, you may be able to “reset” yourbody’s biologic clock.Try to get a night flight and go to sleepwhen the plane takes off; request a blanket if you need one.(Blinders and earplugs may also help.) Your doctor may pre-scribe zolpidem (Ambien) or zaleplon (Sonata), which are rel-atively new short-acting sleeping pills, to help you get to sleepquickly and wake up refreshed. Melatonin is available off the shelf and may work for some people (3 to 12 mg beforebedtime).

When your flight lands, try to adjust to the local timeimmediately: eat and sleep at the locally appropriate times andget a lot of morning daylight to help reset your brain’s biologicclock to the new time zone. If you are flying west, you shouldhave less trouble as long as you get to sleep early (which maybe your own sleep time in the east).

Consider taking a headache medication, such as prescrip-tion Midrin or an off-the-shelf NSAID, before you leave forthe airport and 3 hours later while you are on the plane whenthe flight attendant comes around with beverages. Or you cantry taking a triptan at the gate before takeoff. Be sure to haveheadache medications with you in case you develop a severeheadache in flight or in a foreign country. Keep medications intheir original containers with proper labels and the name of

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your physician. Some countries may require that you have aletter from your doctor, particularly if you travel with opiates(narcotics) or injectable medications. In addition to medica-tions you normally take for headache, your doctor may wantyou to have an opiate or steroid (dexamethasone [Decadron])tablets on hand as backup treatment if your usual treatmentdoes not work.

ALTITUDE HEADACHE

Even more than the temporary “altitude” of airplane cabinpressurization, high altitude in the mountains is a problem forcertain migraineurs. If you spend considerable time at altitudesof 8,000 feet or higher, you may develop headaches whetheryou are biologically vulnerable or not.

Reduce your risk of altitude headache by avoiding alcohol,caffeine, and large amounts of pain medication. Be sure todrink sufficient fluids from the moment you arrive, pace your-self, do not overexert yourself, and take your headache med-ication as needed. For some patients, acetazolamide (Diamox)250 mg three times per day can prevent altitude headaches. Itsmajor side effects include increased urination and tingling inthe fingers and around the mouth. We sometimes prescribedexamethasone (Decadron) 2 to 4 mg up to three times perday for a few days, beginning on the day patients arrive athigh altitude; it is relatively safe if used for just a few days.

CONCLUSION

Holidays and travel are often fun, but they can be ruined byheadaches. Proper treatment before and during these suscepti-ble times can make a big difference in how you feel.

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We truly hope that you have found this book useful inyour search for relief and comfort. Doctors and researchersnow can argue that we know as much about the underpin-nings of migraine and related disorders as we do about otherneurologic conditions such as epilepsy, Parkinson’s disease,multiple sclerosis, and Alzheimer’s disease. In fact, new data tellus that the burden of illness and prevalence of headache aregreater than for all of those diseases combined! The WorldHealth Organization now lists the disability secondary tomigraine in the top 20 list of worldwide disabling disorders.

The future is looking brighter for headache sufferers interms of achieving the dream of control and prevention ofheadache and being treated with credibility, understanding,and compassion. As the mysteries of the causes of migrainebegin to unfold, and as new techniques in genetics, molecularbiology, and functional imaging are improved, new targets arebeing identified for potential therapies. We think treatmentand understanding of headache will continue to change forthe better in this first decade of the new millennium. Due toour new knowledge of the disease, the development of newmedications for migraine looks to be just around the corner,and behavioral help has also added greatly for those affected.Finally, in 2006, a US national Board certification forHeadache Medicine became available as care providers tookknowledge-based tests on all headache disorders. Remember:you are not alone, and there are now an increasing number ofcare providers committed to your help!

144

A F INAL WORD

145

AAbdominal migraine, 124Absenteeism, 5Accolate, 91Acetaminophen (Tylenol), 29, 43–44, 55, 122,

125, 135overuse of, 43

Acetazolamide (Diamox), 95, 143Acetylsalicylic acid (Aspirin), 4, 55, 122, 135, 140Acupressure, 106Acupuncture, 106Adjustment, 106Advil. See Ibuprofen (Advil)Air travel, 141–143Alcoholic beverages, 27, 140Alcoholism, 42Allergy headache, 20Allodynia, 76, 77–78Almotriptan (Axert), 60, 64Alprazolam (Xanax), 73Altitude headache, 143Ambien, 142Amerge, 60, 65, 132Amitriptyline (Elavil), 83–84, 127Amlodipine (Norvasc), 81t, 88Anacin, 55Analgesic rebound headache, 3, 5, 43–44Anaprox, 55, 69, 70, 122, 125–126, 131Anapsine, 116Ancient Egyptians, 1, 2fAnsaid, 69, 131Antianxiety agents, 73Antidepressants, 41, 82–83, 83tAnti-inflammatory medications, 4Antinausea medications, 74Antipsychotic medications

atypical, 91Anxiety, 31, 141

children, 124–125coexisting with headache, 40–41symptoms, 41

Appointment book, 105Arthritis, 30Aseptic necrosis of bone, 94Aspartame, 28Aspirin. See Acetylsalicylic acid (Aspirin)Atenolol (Tenormin), 79, 80tAtivan, 73Aura

defined, 10headache

with or without, 8–10neurologic events resembling stroke, 10–11

Autogenic training, 101Autoinjector, 61Axert, 60, 64

BBaclofen (Lioresal), 75Barbiturates, 47–48

overuse of, 43Basilar-type migraine, 57Beer, 27Benadryl, 116Beta-blockers, 79–82, 80t, 88

Bextra, 71, 91, 131Biofeedback, 102–103, 104fBlack cohosh, 137Blocadren, 79, 80tBloodletting, 1Blood vessels, 24–25Body scan, 101–102Botulinum toxin injections (Botox), 89Brain, 23–24Brainstem, 24Breast-feeding, 136

medications to avoid, 136tBreslau, Naomi, 40–41Burstein, Rami, 26, 76Buspirone (Buspar), 73Bussone, Gennaro, 32, 97Butalbital, 44, 56, 69, 87

analgesics containing, 72medications containing, 47–48

Butorphanol tartrate (Stadol nasal spray), 72,73, 117

Butterbur, 109

CCady, Roger, 31Cafergot. See Ergotamine tartrate (Cafergot)Caffeine, 28, 29, 133

content of food and drugs, 30tmedications containing, 47–48overuse of, 43

Caffeine rebound headache, 45–46Calan, 81t, 88, 94, 95Calcium channel blockers, 88Capsaicin, 95Carbamazepine (Tegretol), 86Cardene, 88Cardizem, 81t, 88Carisoprodol (Soma), 75Cataflam, 70Celebrex, 71, 91, 131Celecoxib (Celebrex), 71, 91, 131Celexa, 84Central sensitization, 26Central theory, 23–24Champagne, 27Chasteberry, 137Children, 120–138, 121f

anxiety, 124–125evaluation, 123headache types, 120–122prevention, 126–127psychological factors, 124–125tension-type headache, 121ftreatment, 125–128worry, 122–123

Chiropractic therapy, 106Chlorpromazine (Thorazine), 74, 117Chocolate

caffeine content of, 30tChronic daily headache, 16–17Chronic migraine with medication overuse, 3, 5Chronic tension-type headache, 12Cialis, 49Citalopram (Celexa), 84Civamide, 96

INDEX

146

Clarithromycin, 64Clonazepam (Klonopin), 75Clorazepate (Tranxene), 73Cluster headache, 12–14, 32

causes, 31–32family history, 13prevention, 94–95surgery, 96–97treatment, 92–97, 118women, 13

Cocoacaffeine content of, 30t

Codeine, 44, 72Coenzyme Q10, 109Coffee, 55

caffeine content of, 30tCognitive therapy, 103–104Coital headache, 15Cold stimulus, 16Common migraine. See Migraine, aura, withoutCompazine, 74, 116Compresses, 10Computed tomography (CT), 35, 36Corgard, 79, 80tCox-2 inhibitors, 91CT, 35Cutaneous allodynia, 26Cyclobenzaprine hydrochloride (Flexeril), 75Cyproheptadine (Periactin), 82t, 89,

126–127, 135

DDaily logs. See Headache calendarDanger signals, 33–34Darvon, 72Darwin, Erasmus, 2Decadron, 73, 143Demerol, 85, 115, 117–118Depacon, 48, 115, 117Depakote. See Divalproex sodium

(Depakote, Epival)Depression, 31

coexisting with headache, 40symptoms, 41

Desipramine (Norpramin), 83Desyrel, 83Detoxification, 48Dexamethasone (Decadron), 73, 143DHEA 45. See Dihydroergotamine (DHEA 45)Diamox, 95, 143Diaries. See Headache calendarDiazepam (Valium), 73, 75Diclofenac (Cataflam), 70Diet, 104Dietary triggers, 128Dihydroergotamine (DHEA 45), 48, 68,

115–116, 126, 133Dilantin, 86Dilaudid, 72Diltiazem (Cardizem), 81t, 88Diphenhydramine (Benadryl), 116Disabling migraine, 44Divalproex sodium (Depakote, Epival), 81t, 86,

94, 117, 127Doctor-patient relationship, 111–113, 112f

Doctor’s role, 35–37Doxepin (Sinequan), 83, 84, 127Droperidol (Anapsine), 116–117Drug abuse, 42

EEating, 104Effexor XR, 84Elavil, 83–84, 127Electrical stimulation, 107Electroencephalogram, 37Eletriptan (Relpax), 60, 64Emergency department, 114–119, 114f

migraine treatment, 115–118Emetrol, 74Epidural blood patch, 21Episodic and chronic paroxysmal hemicrania, 15Episodic tension-type headache, 11–12Epival. See Divalproex sodium (Depakote,

Epival)Equal, 28Ergotamine rebound headache, 45Ergotamine tartrate (Cafergot), 24–25, 29,

67–68, 74, 94overuse of, 43

Ergots, 67–68, 93Escitalopram (Lexapro), 84Esgic, 44, 56, 72, 126Esomeprazole (Nexium), 95Estradiol, 131Estrogen, 49Etodolac (Lodine), 70Evening primrose oil, 137Excedrin Migraine, 29, 55Exercise, 105, 107, 139Exertional headache, 14, 33

treatment, 15–16Eye-related headache, 20

FFalse symptoms, 38–39Family conflict, 124Female. See WomenFenoprofen (Nalfon), 70Feverfew, 108–109Fioricet, 44, 56, 72, 126Fiorinal, 44, 47–48, 56, 69, 72, 87Flexeril, 75Flunarizine (Sibelium), 81t, 88Fluoxetine, 49, 84, 85Flurbiprofen (Ansaid), 69, 131Folk remedies, 2Food

caffeine content of, 30thangovers, 140

Frova, 60, 65Frovatriptan (Frova), 60, 65

GGabapentin (Neurontin), 81t, 87, 95, 127Gabitril, 81tGait, 107Gangliorhizolysis, 96Garlic, 110Genetics, 39

147

Gentle triptan, 65Geodon, 91Ginger, 110Ginseng, 110Glaucoma, 20Goadsby, Peter, 32Graham, John, 24Granisetron (Kytril), 74, 75, 117Grasses, 20Group therapy, 104Guarana, 110

HHangover headache, 140Hay fever, 20Headache. See also Cluster headache;

Tension-type headacheallergy, 20altitude, 143analgesic rebound, 3, 5, 43–44caffeine rebound, 45–46causes, 7, 22–32, 38–39chronic daily, 16–17classification, 7coital, 15ergotamine rebound, 45exertional, 14, 33

treatment, 15–16eye-related, 20factors contributing to, 39–40hangover, 140history of, 1–2holiday, 138–139, 139fice cream, 16idiopathic stabbing, 14impact on life, 37impact on society, 3–6major, 7tmedication overuse, 43–44muscle contraction, 30new-onset, 34posttraumatic, 17–18rebound. See Rebound headachesex, 15sinus, 4, 14, 18–19spinal tap, 21stabbing

treatment, 15–21suicide, 13types of, 7–21

Headache calendar, 50, 98–99, 99f, 104,127–128

Headache ice-pillow, 107Headache Impact Test (HIT), 55, 56Heat, 106–107Hemicrania continua, 17Hemiplegic migraine, 57Hemorrhage, 33Herbals, 108–109Hidden epidemic, 5High blood pressure, 10Hippocrates, 1HIT, 55, 56Holiday headache, 138–139, 139fHomeopathy, 108

Hormones, 91, 136–137Hydrochloride (Demerol), 115Hydrocondone-acetaminophen (Vicodin), 72Hydromorphone (Dilaudid), 72Hydroxyzine (Vistaril), 74, 117

IIbuprofen (Advil), 4, 55, 70, 122, 125, 131Ice cream headache, 16Idiopathic stabbing headache, 14Imbalances, 106Imigran, 57–61, 92, 115–118, 126, 132, 136Imipramine (Tofranil), 83–84, 127Imitrex, 57–61, 92, 115–118, 126, 132, 136Inderal, 64, 79, 80t, 127Indocin. See Indomethacin (Indocin)Indomethacin (Indocin), 15, 16, 17, 48, 70Inpatient therapy, 118–119Itraconazole, 64

JJet lag, 141

KKeppra, 88Ketoconazole, 64Ketoprofen (Orudis), 55, 69, 70, 122, 125, 131Ketorolac (Toradol), 70, 115Klonopin, 75Kudrow, Lee, 31–32Kytril, 74, 75, 117

LLabor

lost, 5Lance, James, 25–26Lansoprazole (Prevacid), 95Leeches, 1Leone, Massimo, 32, 97Leukotriene antagonists, 91Levetiracetam (Keppra), 88Levitra, 49Lexapro, 84Lifestyle changes, 104–105, 105fLioresal, 75Lipton, Richard, 31, 52, 109Lithium carbonate, 32, 94Lodine, 70Lopressor, 79, 80tLorazepam (Ativan), 73Lumbar puncture, 37

MMagnesium, 24, 109Magnetic resonance angiography (MRA), 35, 36Magnetic resonance imaging (MRI), 35, 36

scanner, 37Malingering, 38–39MAOI, 71, 82, 85, 89Marks, David, 95–96Massage, 106–107Maxalt, 60, 64, 82Meclofenamate (Meclomen), 69, 70, 126, 131Meclomen, 69, 70, 126, 131Medication overuse headache, 43–44

148

Medications, 50–78, 139abortive treatment, 50caffeine content of, 30tdoctor need to know about, 59preventive treatment, 50–51symptomatic treatment, 50

Mefenamic acid (Ponstel), 70Melatonin, 15, 96Melphalan, 142Menarche, 130Meningitis, 33, 122Menstrual cycle, 27, 129, 130fMenstrual migraine, 130–133

treatment, 131–132Meperidine (Demerol, Pethidine), 115,

117–118Metaxalone (Skelaxin), 75Methergine, 82, 90, 95Methocarbamol (Robaxin), 75Methylergonovine (Methergine), 82, 90, 95Metoclopramide (Reglan), 74, 116, 135Metoprolol (Lopressor), 79, 80tMIDAS scale, 53, 54Midrin, 56, 69, 85, 122, 126, 142Migraine, 4, 20

abdominal, 124aura

with, 8, 10without, 8–9

basilar-type, 57causes, 22–29coexisting with headache, 40–41defined, 7–8diagnosis, 9, 9tdisabling, 44equivalent, 10, 123–124hemiplegic, 57low-level

treatment, 55–57with medication overuse, 3, 5menstrual, 130–133

treatment, 131–132personality, 39pregnancy, 134–135prevention of, 79–92severity evaluation, 52–55vs. tension-type headache, 31, 75–76transformed

with medication overuse, 43–44treatment, 27ttriggers, 27–29, 28f, 28tunderdiagnosed, 3women, 8

Migraine Disability Assessment (MIDAS) scale,53, 54

Minerals, 108–109Monoamine oxidase inhibitor (MAOI), 71, 82,

85, 89Monosodium glutamate (MSG), 28Montelukast (Singulair), 91Morphine, 72Moskowitz, Michael, 25MRA, 35, 36MRI, 35, 36

scanner, 37

MSG, 28Muscle contraction headache, 30

NNabumetone (Relafen), 70Nadolol (Corgard), 79, 80tNalfon, 70Naprosyn, 70Naproxen (Naprosyn), 70Naproxen sodium (Anaprox), 55, 69, 70, 122,

125–126, 131Naratriptan (Amerge), 60, 65, 132Narcotics, 47–48Nardil, 71Naturopathy, 108Neck roll, 103fNefazodone, 64Nelfinavir, 64Nerves, 2Neurogenic inflammation theory, 25Neurologic examination, 36Neurologic symptoms resembling stroke, 33Neurontin, 81t, 87, 95, 127Newman, Larry, 132New-onset headache, 34Nexium, 95Nicardipine (Cardene), 88Nifedipine (Procardia), 48Nisoldipine (Sular), 81t, 88Nitroglycerin, 49Nonheadache drugs

causing headache, 48–49Nonprescription pain medication, 4Nonsteroidal anti-inflammatory medications,

15–16, 56, 69, 70–71, 90–91, 140Norpramin, 83Nortriptyline (Pamelor), 83, 84, 127Norvasc, 81t, 88Nutrasweet, 28

OOccupations, 107Off-the-shelf

defined, 4Off-the-shelf pain relievers, 3, 5f

caffeine content of, 30toveruse of, 4, 5, 43side effects, 3

Olanzapine (Zyprexa), 91, 93Omeprazole (Prilosec), 95Ondansetron (Zofran), 74, 75, 117, 135Opiates, 72–73, 117–118

overuse of, 43Oral contraceptives, 133–134Orudis. See Ketoprofen (Orudis)Over-the-counter

defined, 4Oxycodone (OxyIR), 72Oxygen, 92OxyIR, 72

PPain, 13

overuse of medication, 42Pamelor, 83, 84, 127

149

Panic attackscoexisting with headache, 40–41

Pantoprazole (Protonix), 95Parnate, 71Paroxetine, 49, 84Paroxysmal hemicrania

treatment, 15–21Passive techniques, 106–108Patient-doctor relationship, 111–113, 112fPatient histories, 35, 37Paxil (paroxetine), 49, 84Periactin, 82t, 89, 126–127, 135Perimenopausal, 136–137Personal time, 105, 105fPetasites (butterbur), 109Pethidine, 115, 117–118Phenelzine (Nardil), 71Phenergan, 74, 115, 117, 125Phenobarbital, 87Phenytoin (Dilantin), 86Phobias

coexisting with headache, 40–41Photopsia, 10Phrenilin, 44, 72Physical and occupational therapies, 106–107Pollen, 20Ponstel, 70Postpartum period, 135–136Posttraumatic headache, 17–18Posture, 30, 107Prednisone, 73, 93Pregnancy

migraine, 134–135Prescription drugs

caffeine content of, 30toveruse of, 43

Prevacid, 95Prilosec, 95Procardia, 48Prochlorperazine (Compazine), 74, 116Progesterone, 132Progressive relaxation, 101Promethazine (Phenergan), 74, 115, 117, 125Propoxyphene (Darvon), 72Propranolol (Inderal), 64, 79, 80t, 127Prostaglandins, 129Protonix, 95Proton pump inhibitors, 49, 95Protriptyline (Vivactil), 84Prozac (fluoxetine), 49, 84, 85Psychiatric disorders

coexisting with headache, 40–41Psychogenic factors, 38Psychological factors, 38–42

children, 124–125Psychotherapy, 104Pulsed therapy, 131

QQuestions, 112–113Quetiapine (Seroquel), 91

RRadiofrequency trigeminal ablation

(gangliorhizolysis), 96

Rags, 2Raskin, Neil, 24Rebound headache, 5, 17, 43–49

recognition, 45treatment, 47–48

Red wine, 27Reglan, 74, 116, 135Relafen, 70Relaxation techniques, 100–101Relpax, 60, 64Rescue medications, 72–75Reye’s syndrome, 122Rhythmic breathing, 100Riboflavin, 109, 137Risperdal (Risperidone), 91Risperidone, 91Ritonavir, 64Rizatriptan (Maxalt), 60, 64Robaxin, 75Rodin thinker position, 92Rofecoxib (Vioxx), 91, 126, 131Room

dark, quiet, 10Rozen,Todd, 109

SSandor, Peter, 109Scheduling, 138Schoenen, Jean, 109Scotoma, 10Selective serotonin reuptake inhibitors (SSRI),

82, 84–85Sensitization, 76–77Seroquel, 91Serotonin, 24Serotonin2 antagonists, 89–90Serotonin connection, 40–41Serotonin receptors, 25Sertraline (Zoloft), 84Sex headache, 15Showers, 107Sibelium, 81t, 88Sildenafil citrate (Viagra), 49Sinequan, 83, 84, 127Singulair, 91Sinus

diagram, 19fheadache, 4, 14, 18–19medications, 4

Sinusitis, 19Skelaxin, 75Sleep, 139Smoking, 134Society, 3–6Soft drinks

caffeine content of, 30tSoma, 75Sonata, 142Spinal tap, 37Spinal tap headache, 21SSRI, 82, 84–85Stabbing headache

treatment, 15–21Stadol nasal spray, 72, 73, 117Statdose, 61

150

Step care, 51–52Steroids, 73Stewart,Walter, 53Stratification of care, 51–52Stress, 29, 39–40, 138, 141Stroke

neurologic events resembling, 10–11Substance abuse, 42Suicide headache, 13Sular, 81t, 88Sumatriptan (Imitrex, Imigran), 57–61, 92,

115–118, 126, 132, 136

TTadalafil (Cialis), 49TCA, 82, 83–84, 85Tea

caffeine content of, 30tTegretol, 86Temporomandibular joint (TMJ)

dysfunction, 14, 20, 30Tenormin, 79, 80tTENS, 108Tension

signs of, 138Tension-type headache, 20, 69

causes, 29–31children, 121fchronic, 12defined, 11–12episodic, 11–12migraine, 31vs. migraine, 75–76triggers, 30

Thorazine, 74, 117Tiagabine (Gabitril), 81tTigan, 74Timolol (Blocadren), 79, 80tTizanidine (Zanaflex), 75TMJ dysfunction, 14, 20, 30Tobacco stamps, 2Tofranil. See Imipramine (Tofranil)Topiramate (Topamax), 81t, 87–88, 95, 127Toradol, 70, 115Tramadol (Ultram), 72Transcutaneous electrical nerve stimulation

(TENS), 108Transformed migraine with medication

overuse, 43–44Tranxene, 73Tranylcypromine (Parnate), 71Trazodone (Desyrel), 83Trephination, 1, 1fTricyclic antidepressants (TCA), 82, 83–84, 85Trigeminal neuralgia, 20–21Trigeminovascular system, 23f, 25Trigger point injections, 107–108Trimethobenzamide (Tigan), 74Triptan, 10, 57–59, 85, 90, 92, 142

description, 60effectiveness, 58gentle, 65overuse of, 43prohibited use, 68–72safety, 58

side effects, 58–59types, 60–61

Triptan rizatriptan (Maxalt), 82Troleandomycin, 64Trust, 112fTylenol. See Acetaminophen (Tylenol)Tyramine, 27

UUltram, 72Ultrasonography, 107Unifying theory, 25Unwinding, 138, 139

VValdecoxib (Bextra), 71, 91, 131Valium, 73, 75Valproate sodium (Depacon), 48, 115, 117Vardenafil (Levitra), 49Vascular theory, 24–25Venlafaxine (Effexor XR), 84Verapamil (Calan), 81t, 88, 94, 95Viagra, 49Vicodin, 72Vioxx, 91, 126, 131Visible aura, 11fVistaril, 74, 117Visual imagery, 101, 102fVitamin(s), 108–110Vitamin A, 49Vitamin B2 (riboflavin), 109, 137Vitamin E, 109Vitex (chasteberry), 137Vivactil, 84Vomiting, 1

WWeeks, Randall, 39Welch, K.M.A., 24Willis,Thomas, 1, 24Wolff, Harold, 24, 39Women, 129–137

cluster headache, 13increased migraine susceptibility, 129tmigraine, 8

XXanax, 73

YYang, 106Yin, 106

ZZaleplon (Sonata), 142Zanaflex, 75Zarfirlukast (Accolate), 91Ziprasidone (Geodon), 91Zofran, 74, 75, 117, 135Zolmitriptan (Zomig), 60, 62–63, 93, 115, 132Zoloft, 84Zolpidem (Ambien), 142Zomig, 60, 62–63, 93, 115, 132Zonisamide (Zonegran), 81t, 88Zyprexa, 91, 93