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Woman With Dull Daily Headaches and Episodic “Knockout” Attacks


A 40-year-old woman reports increasingly frequent and severe headaches during the past few months. She has had boutsof severe headaches since college, and episodic migraine was diagnosed a decade ago. She uses over-the-counter products(ibuprofen, ketoprofen, or aspirin) at the onset of an attack; if these fail to relieve symptoms, she takes hydrocodone/acetaminophen. During her worst attacks, she is typically forced to halt her activities, is unable to eat or drink, and mayvomit. For unresponsive or persistent (more than 24-hour) attacks, her husband drives her to the urgent care centerfor intravenous hydration, intramuscular promethazine, and additional doses of hydrocodone/acetaminophen. Accordingto the patient, a visit to the urgent care center “completely ruins our day.”


A 40-year-old woman reports increasingly frequent and severe headaches during the past few months. She has had boutsof severe headaches since college, and episodic migraine was diagnosed a decade ago. She uses over-the-counter products(ibuprofen, ketoprofen, or aspirin) at the onset of an attack; if these fail to relieve symptoms, she takes hydrocodone/acetaminophen. During her worst attacks, she is typically forced to halt her activities, is unable to eat or drink, and mayvomit. For unresponsive or persistent (more than 24-hour) attacks, her husband drives her to the urgent care centerfor intravenous hydration, intramuscular promethazine, and additional doses of hydrocodone/acetaminophen. Accordingto the patient, a visit to the urgent care center "completely ruins our day."During the past 9 to 12 months, the attacks have slowly evolved into bilateral, dull headaches that occur virtuallyevery day, with additional "knockout" attacks once or twice weekly. During this time, the patient has averaged atleast 1 urgent care center visit--and up to 3 visits--per week. She uses multiple doses of hydrocodone/acetaminophen atleast 3 days per week, although these are increasingly ineffective.The patient had been seeing another physician, but was frustrated by the ineffective treatment regimen and angeredthat one of the nurses in that physician's office had given her a brochure about chemical dependency. She wants to takecontrol of her headaches, and now seeks your care.Results of her physical and neurologic examinations are unremarkable, as is the rest of her history. Scans from previousyears are all normal.

Does migraine account for all this woman's symptoms?How would you change the treatment regimen?What preventive agents might be appropriate for this patient?


Primary care doctor:

Is migraine the correct diagnosis inthis woman's case?

Headache specialist:

Migraine is only part of the diagnosis.Although migraines account for this patient's "knockoutattacks," her headaches are no longer purely episodic--which puts her in a diagnostic gray zone. A clinicianfriendly,all-encompassing, universally accepted chronicheadache classification system does not exist. Accordingto the International Headache Society diagnostic hierarchy,this patient has both migraine and chronic tensiontypeheadaches

(Table 1).


She also fulfills the more intuitivecriteria for chronic daily headache (CDH) proposedby other researchers.


Whichever classification system is used, the fact remainsthat she has experienced a headache more than 15days per month for at least 1 month--a key feature ofCDH. Increasing the use of analgesics and other acutemeasures to the point of daily or every-other-day administrationis rarely effective. In fact, this approach may exacerbatethe condition.


It's encouraging, by the way, that a migraine diagnosiswas made in this woman's case. Migraine is not diagnosedin more than half of the 28 million American migrainesufferers (18% of women, 6% of men in the generalpopulation), in part because patients do not seek treatment--and because clinicians are sometimes unaware ofthe criteria used to make the diagnosis. This patient fitsthe stereotypic profile of a patient with migraine: a womanwhose headaches began in late adolescence or early 20s,with frequency and severity that have escalated over manyyears.

Primary care doctor:

A regimen of analgesic narcotics,promethazine, and hydration may work for her episodicattacks, but isn't it clearly ineffective for this patient's unremittingpain?

Headache specialist:

The dynamic of her illness haschanged. Yet the response to this change has been to simplyescalate the frequency of expensive, time-consumingtrips to the urgent care center, which yields only shorttermrelief. Furthermore, her physician's nursing staff hashinted that she is narcotic-seeking--an antagonistic approachthat, in my opinion, is unwarranted. The problemrests not with the patient but with the redundant, inappropriatetherapy.It is crucial to recognize when a treatment approachhas become ineffective and when a new strategy is indicated.As a former mentor once said to me: "If you want toget out of a hole, you first need to quit digging."

Primary care doctor:

What do you suggest?

Headache specialist:

I'd recommend a proactive regimeninstead of the current reactive one. By definition, CDH occursin a predictable pattern. From this point on, the patient'stherapy should consist of drug and nondrug optionsaimed at preventing, or at least eliminating, her headaches.She needs to completely avoid the urgent care center.

Primary care doctor:

What approach would yourecommend?

Headache specialist:

Successful therapy, of course, dependson an accurate diagnosis. A detailed history is thereforekey--it is the single most important tool for diagnosingany primary headache disorder.


I would ask the patient to keep a headache diary, which can help confirm the diagnosisof CDH. She needs to record the times at which herheadaches occur, their intensity, and any activities, foods,or other factors that precede or exacerbate the headache.She must also list any medications that she takes, as wellas her response to these agents.I would review the diary with the patient at a followupappointment in 4 weeks. During that visit, it is importantto demonstrate concern for the patient's overall wellbeingand reinforce the idea that the aim of the visit is notsimply for the physician to write another prescription. Aheadache diary can elicit much valuable informationabout concerns that need to be addressed, including dietaryproblems (such as skipped meals), poor sleephabits, stress, interpersonal problems (such as maritalconflict), and delays in taking prescribed medication at theonset of an attack. Highlighting unhealthy behaviors--ifthese exist--also helps demonstrate that sometimes takingmedication is not enough to control an illness.This patient's headaches are getting worse of theirown accord and because she is overusing acute agents--not because of interpersonal conflict. But it is important toexplore all potential causes of worsening headaches. Adiary can help you rule out "life problems" or stimulate adiscussion about those problems when they exist.For patients with comorbid depression or anxiety, areferral for psychological evaluation and/or counseling isimperative. Up to 60% of patients with CDH experience areduction in headache frequency or severity followingpsychological intervention.


Screening for depression inpatients with CDH--with the Beck Depression Inventoryor similar instrument--may be very useful.In addition to implementing changes based on patternsnoted in a headache diary, patients may wish to considerhealthy lifestyle changes. For example, stress-managementmodalities, such as biofeedback, yoga, aerobicexercise, or meditation, may be beneficial. It is importantto discuss these options with patients, because they aremore likely to adhere to a program that is the result of ajoint decision.

Primary care doctor:

Stress-management measures alonearen't likely to prevent all headaches. This woman is alsogoing to need medication.

Headache specialist:

I agree. Daily preventive medicationis recommended for patients with 4 or more headache attacksper month who do not obtain relief with appropriateacute therapy or whose recurrent attacks significantly disrupttheir life. Prophylactic therapy is also warranted forpatients who may have infrequent migraines (for example,1 attack every 2 months) but who require prolonged bedrest (3 or 4 days) per attack.

Primary care doctor:

Which preventive agent(s) might bemost appropriate for this patient?

Headache specialist:

Few well-designed controlled trialsexist to help guide selection of an initial agent; thus,recommendations are based mainly on small, open-labelstudies; case reports; and clinical experience.


The tricyclicantidepressants are the most extensively usedmedications. I have found them to be the most effectiveprophylactic agents.


Like many experts, I regard themas the treatment of choice for CDH. Anecdotal evidenceexists for a spectrum of other drugs, including selectiveserotonin reuptake inhibitors (SSRIs), tetracyclic antidepressants,anticonvulsants, and monoamine oxidase inhibitors(MAOIs).


Before you select a specific agent, consider whetherthe patient has a comorbid disorder. By treating multipleproblems with a single agent, you simplify therapy, increasecompliance, reduce the potential for adverse effects,and make it easier to evaluate treatment efficacy.Insomnia, for example, is common among patientswith CDH. In this setting, a sedating tricyclic, such asamitriptyline or doxepin, is reasonable. If insomnia is not afactor, however, or if a patient reports drowsiness (perhapsattributable to another medication), a less sedatingtricyclic--such as protriptyline or nortriptyline--might beprescribed. Depression is also common in patients withCDH. Antidepressants--such as SSRIs--may be used incombination with tricyclics in this setting. As noted, however,the SSRIs tend to be less effective than tricyclics forCDH. Studies suggest that the analgesic properties of thetricyclics are independent of serotonin reuptake inhibition,which may explain why they are more effective thanSSRIs. Some experts prefer an antidepressant, such asvenlafaxine, with a dual mechanism of action that preventsreuptake of both serotonin and norepinephrine.A β-blocker or calcium channel blocker may be indicatedin the presence of cardiac disease or hypertension.A patient with seizures or mood disorder may benefitfrom an anticonvulsant.

Primary care doctor:

What constitutes a good response totherapy?

Headache specialist:

In most studies, a response is definedas a reduction of 50% or more in frequency or intensity ofheadaches.


It is best to "start low and go slow" with a preventiveagent. Advise patients that it may take a month for themedication to achieve its full effect. Schedule follow-up visitsevery 3 to 6 weeks until the headaches are better controlled,at which point the visits can be scheduled aboutevery 6 months.If a patient reports no response, the dosage can beincreased. If 1 or 2 dosage adjustments fail to yield acceptablerelief, or if intolerable adverse effects occur, consideranother medication. Sometimes a different agent in thesame class works well.

Primary care doctor:

What do you recommend for breakthroughheadaches?

Headache specialist:

Several options are available. Acuteattacks at home can be managed with triptans, subcutaneousor intramuscular dihydroergotamine, NSAIDs(including cyclooxygenase-2 inhibitors), or oral and injectablemuscle relaxants, such as orphenadrine, among others. Oral and intramuscular corticosteroids are sometimesused if the breakthrough headaches are severe and refractoryto conventional abortive agents.Limits of use must be established to prevent the developmentof rebound headaches. I tell patients to limituse to fewer than 3 days per week (although multipledoses on a given day are allowed). Patients who feel theneed to exceed this limit, or who seek help in the emergencydepartment (ED), need to contact their headachespecialist for further evaluation.


In the ED, or for patientsin acute distress in the physician's office, rehydration iscritical. Other options are outlined in

Table 2.

These includeintravenous dihydroergotamine or narcotics, administeredwith an antiemetic; intravenous neuroleptics, corticosteroids,or magnesium; intramuscular ketorolac; andsubcutaneous sumatriptan.

Primary care doctor:

What is the best strategy in the caseof refractory headache pain?

Headache specialist:

If you have exhausted the optionswith which you are comfortable in the outpatient settingand both you and the patient are becoming frustrated, referralto a specialty headache center is probably warranted.2 In addition to maximizing nonpharmacologic options,specialists at these centers may use treatments that arenot standard in primary care practice. One example isMAOI therapy.7 Although many physicians view MAOIsas "risky," they can be effective. The physicians at inpatientheadache centers have experience with MAOI therapy,as well as the necessary support staff--including dietitiansand pharmacists--to provide patient education. It isvital that patients adhere to their therapeutic regimen, andthis goal can be coordinated by the headache specialistand the patient's primary care physician.Chronic headaches require a comprehensive, coordinatedapproach. Creating strategies for optimal care requirestime and effort, but the rewards of such care canbe substantial.




International Headache Society. Classification and diagnosis criteria for headachedisorders, cranial neuralgias and facial pain.


1988;8(suppl 7):10-96.


Welch KM. A 47-year-old woman with tension-type headaches.




Siberstein SD, Lipton RB, Solomon S, Mathew NT. Classification of daily andnear-daily headaches: proposed revisions to the IHS criteria.




Redillas C, Solomon S. Prophylactic pharmacological treatment of chronicdaily headache.




Holroyd KA, O’Donnell FJ, Stensland M, et al. Management of chronic tension-type headache with tricyclic antidepressant medication, stress managementtherapy, and their combination: a randomized controlled trial.




Diamond S, Moore KL. Headache of the month: a 38-year-old woman withintractable migraine.




Freitag FG, Diamond S, Solomon GD. Antidepressants in the treatment ofmixed headache: MAO inhibitors and combined use of MAO in the recidivistheadache patient. In: Rose FC, ed.

Advances in Headache Research.

London: JohnLibbey; 1987:271-275.


Mauskop A, Altura BT, Cracco RQ, Altura BM. Intravenous magnesium sulphaterelieves migraine attacks in patients with low serum ionized magnesiumlevels: a pilot study.

Clin Sci (Colch).


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