Rebound Headache: Keys to Effective Therapy

December 31, 2006

Which of these scenarios is familiarto you? •A local pharmacist calls to say thatyour patient wants another refill for thecombination analgesic containing aspirin,caffeine, and butalbital that youprescribed last week. Pharmacy recordsindicate that this patient has received250 tablets of this medication inthe last 34 days.

Which of these scenarios is familiarto you?

  • A local pharmacist calls to say thatyour patient wants another refill for thecombination analgesic containing aspirin,caffeine, and butalbital that youprescribed last week. Pharmacy recordsindicate that this patient has received250 tablets of this medication inthe last 34 days.
  • Your new patient reports that she hasa migraine attack 2 or 3 times a week.Each attack lasts 24 to 48 hours and requiresher to take 2 to 4 sumatriptantablets. Her first request is that you completea set of disability papers to supporther claim that she cannot work duringher attacks.
  • A patient reports that he has haddaily headaches since a car accident 4years ago.

What these patients have in commonis rebound headache.

Rebound headache is by far themost frequent diagnosis in patientswith daily or almost daily, prolongedheadaches of weeks', months', oryears' duration. Among patients withheadache, those with rebound headachehave the greatest number of officeand emergency department visits,miss the most days from work, andseek the most medications for painrelief.

Many patients with reboundheadache never seek medical adviceand continue to use daily over-thecounter(OTC) analgesics for years.They are unaware of the relationshipbetween their pain medications andtheir continued headaches--that is,that medications used for today'sheadache may "rebound" and causetomorrow's headache.

Rebound headache is not a psychiatricdisorder. It has a biochemicalbasis, and the pain is real. You can helppatients with this condition by takinga careful history and guiding themthrough the process of terminating theoffending pain relief medications. Inthis article, we describe the mostprominent characteristics of reboundheadache and offer a plan for successfultreatment.

CHARACTERISTICS OFREBOUND HEADACHE
This disorder is associated withlong-standing, habitual use of analgesicsand usually presents as daily or almostdaily, prolonged, nonthrobbing,generalized, dull, tension-type pain thatthe patient notices upon awakening orshortly after arising.1-3 If not amelioratedor completely relieved with analgesics,the headache persists all day; itmay become more intense if the patientis active.

These headaches differ from ordinarytension-type headaches, whichalso feature generally mild, bilateral,nonthrobbing pain or pressure butoccur only occasionally, often start inthe late afternoon or evening, and donot limit activities. These headachessubside after a brief rest or simpleanalgesics and may resolve spontaneouslyin 1 to 2 hours. Patients seldomseek medical advice.

Eighty percent of patients with reboundheadache have superimposedmigraine-like attacks--either onesidedor bilateral--that generally aremore frequent, more prolonged, andmore intense than any isolated migraineattack that the patient mighthave experienced in previous years.Approximately 50% of patients with reboundheadaches have recurrent brief,ice-pick-like jabs of head pain.

About half of patients with reboundheadache can recall a specificinjury, illness, surgical procedure, orinfection for which they initiated thedaily analgesics or antipyretics thateventually produced rebound headaches.3 Such events include trauma,such as a direct head or whiplash injury,a low back injury, or a twisted ankle;a surgical procedure that was followedby several days of pain, such asa neurologic or otolaryngologic operationor hysterectomy; or childbirth.Some patients recall that their reboundheadaches were preceded by antipyreticuse for a lengthy flu-like illness.Others report NSAID therapy for jointpain. Patients who cannot recall aspecific precipitating event often notea more gradual development of theheadaches.

Pathogenesis. The pathophysiologyof rebound headache is not yet understood.Although changes appear tooccur in certain serotonin receptorsand in blood platelets,4,5 it is unclearwhether these changes are the causeof the problem or the result of dailymedication use.

Susceptibility. About 99% of thepopulation can use an NSAID daily forarthritis or an opiate daily for metastaticcancer pain and remain free of reboundheadache. The remaining 1%have in previous years used analgesicsoccasionally with no ensuing reboundheadache. However, use of pain medication3 or more times per week increasesthe risk of rebound headachein this small group of patients--perhapsbecause of an undefined change inbody chemistry (Box I). After reboundheadache develops, the medications--including triptans and narcotics--onlydull or briefly eliminate the pain, thencause subsequent headaches.

Medications used prophylacticallyto prevent frequent migraines--ie,β-blockers, calcium channel blockers,antiepileptics, and antidepressants--are ineffective in preventing the frequent,prolonged migraine-like attacksin patients with rebound headache.

Symptoms of depression often developafter patients experience daily oralmost daily headaches. These patientsare often treated with antidepressants,but this treatment is rarely successful.Mild to moderate hypertension developsin some patients with reboundheadache who use NSAIDs.

Unusual manifestations.We haveseen several unusual presentations ofrebound headache at our clinic. Theheadaches may be unilateral or localizedto a small area on one side or evento one orbit. The headaches mightfollow an injury and be erroneouslyclassified as chronic post-traumaticheadache.7 (Chronic--that is, lastinglonger than 8 weeks--post-traumaticheadaches are rebound headachesuntil proved otherwise.8) We havetreated patients who denied takingdaily or almost daily medications in thepast, but experienced a headache patternthat resembled rebound headacheand recovered when the analgesicswere withheld. A few patients de-scribed their headaches as being strictlymigrainous--either frequent migraine,daily migraine, or frequentepisodes of status migrainosus--anddenied any tension-type component. Ifa migraine attack occurs more than 3to 5 days per week, the likely diagnosisis rebound headache.

 Table -Agents that maycause or perpetuaterebound headache
Acetaminophen 

Aspirin 

Drugs that act on opioid receptors 

Ergotamines 

NSAIDs 

Triptans 

Culprit agents. Agents believedto be responsible for rebound headache--alone or in combination--arelisted in the Table. High doses of caffeinecan exacerbate the problem. Thecritical factor is not the amount of medicationused on a given day but thenumber of days each week that 1 ormore of these agents is used.9

In the southern United States,the principal agents associated withrebound headaches are OTC analgesics.In the north, the chief culpritsare analgesics that contain butalbitaland caffeine (Box II). In Europe andother parts of the world, ergotaminesmay be purchased without a prescriptionand are a major cause ofrebound headache.

Rebound headache that developsfrom daily analgesic use may be perpetuatedby pain-relief agents takenonly 1 or 2 days a week or even lessoften. A nurse at our clinic who experienced3 years of daily headaches followinga whiplash injury used acetaminophenor ibuprofen daily for thefirst year and reduced the use to only1 or 2 days a week for the next 2years. She was told that her continuedheadaches were likely the result ofthis minimal analgesic use. After shefollowed our instructions to completelydiscontinue the offending agents,her daily headaches ceased in 9 days.During the following 4 years, she hadtension-type headaches only once ortwice a month and migraine attacks 3or 4 days each year.

DIAGNOSIS

Any patient who complains ofheadaches requires a careful headachehistory, a medical history, a review ofsystems, and a thorough neurologicexamination. Include in the history thedate of headache onset and the frequency,duration, and treatment ofeach attack. If the attacks do not occurdaily, ask whether the patient has anyheadache pain on the other days andinquire about the pain-relief medicationsbeing used on those other days(or days without bad headaches).There is no laboratory test thatdetects rebound headache. However,it is the likely diagnosis in a patientwho presents with frequent, prolongedtension-type headache (with orwithout associated migraines) if thehistory and physical and neurologicexamination fail to indicate anotherprobable cause. The diagnosis can besuspected from the history and isconfirmed by gradual cessation ofdaily headaches after abrupt, totalwithdrawal of the offending analgesics.Other possible causes of frequentheadache include chronic lung disease,extreme hypertension, myxedema,and papilledema. If the patientpresents with daily headaches ofmore than 6 months' duration and thehistory and physical examination areotherwise normal, the likelihood of atumor or space-occupying lesion issmall and neuroimaging studies canbe deferred.

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MANAGEMENTSTRATEGIES

Successful management requiresthat you spend sufficient time with patientsto give a detailed explanation ofthe problem and a description of thepositive results achieved with other patientswith this condition. An initial visitof 45 to 60 minutes is generally necessaryto obtain the full history, examinethe patient, and provide instructions.Successive 20-minute visits may bescheduled every 4 to 8 weeks. Treatmentresults are less successful ifthese steps are rushed.Give patients a written list ofagents to avoid and instructions aboutrescue medications, such as dihydroergotamine(DHE), for excruciatingheadache. Teach them how to selfadministerDHE. Ask them to keep adaily headache log, and schedule a returnvisit in 4 to 8 weeks.Rebound headache is describedin patient education material distributedat our clinic. You can access thisby e-mail at: john.warner@mcmail.vanderbilt.edu.

Treatment goal.

After abruptlystopping the offending agents, approximatelyhalf of patients experience nowithdrawal symptoms. The other halfnote that their headaches are more intensefor the first 2 to 7 days (anotherjustification for the term "rebound"headache). Thereafter, improvement isslow and gradual. The daily tensiontypeheadaches become less intenseand last fewer hours. The migraine-likeattacks become less frequent, and theirintensity and duration decrease. Eventually,the patient has 1 complete headache-free day, then 2 such days, thenmore than half the days each month.The treatment goal at our clinic is6 consecutive headache-free days. Patientswho resume taking the offendinganalgesics before attaining thisgoal risk the return of frequentheadaches.

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In the interim, the patient can usesubcutaneous injections of DHE, 1 mg,for excruciating headache. No morethan 2 injections, at least 2 hours apart,are to be used in a 24-hour period.Alternatives to DHE are intravenousprochlorperazine, 10 mg by slowpush, or intravenous or intramusculardroperidol, 2.5 mg. Approximately halfof the patients who cease having dailyheadaches never use rescue medications,but they appreciate the securityof knowing they have an agent availableif the pain becomes unbearable.Contraindications to DHE use are infrequent;they include severe hypertensionand coronary artery disease.

Results at our clinic.

In a recentprospective study at our clinic of 50consecutive adults with suspected reboundheadache, 39 (78%) discontinuedthe offending medications.

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The11 patients who did not stop the medicationsreported continuing dailyheadaches. Thirty (77%) of the 39 patientswho stopped the medications experiencedgradual termination of dailyheadaches and reached the goal of 6consecutive headache-free days. Thetime required to reach this goal variedfrom 3 to 325 days (mean, 91 days).Eight of the patients who had notachieved the 6-day goal showed someimprovement, which ranged from lessintense headaches to 4 or 5 consecutiveheadache-free days. The remainingpatient had a history of more than10 years of constant, daily tension-typeheadache; he previously had failed torespond to 15 different medicationsprescribed at another university headachecenter. His headaches persistedfor more than a year after he discontinuedpain medications. Thus, amongthe patients who stopped taking the offendinganalgesics, treatment failedcompletely in only 1 patient (2.6%).A review of the records of otherpatients at our clinic shows that occasionallyit may take as long as 14, 16,or even 20 months to reach the 6-dayheadache-free goal.

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Such patientsneed to be seen regularly and encouragedto "stick with the program."Depression symptoms and hypertensionthat may have accompanied reboundheadache usually resolve whenpatients recover. In addition, overallquality of life markedly improves.

Recurrence.

After reaching the6-day goal, patients may experience infrequenttension-type and/or migraineheadaches. They can use the previouslyforbidden analgesics once ortwice each week. If they exceed thislimit, they are at risk for recurrence ofrebound headache.

References:

REFERENCES:


1.

Mathew NT. Medication misuse headache.Cephalalgia. 1998;18(suppl 21):S34-S36.

2.

Solomon S, Lipton RB, Newman LC. Clinical featuresof chronic daily headache. Headache. 1992;32:325-329.

3.

Warner JS. The outcome of treating patients withsuspected rebound headaches. Headache. 2001;41:685-692.

4.

Srikiatkhachorn A, Puangniyom S, GovitrapongP. Plasticity of 5HT2A serotonin receptor in patientswith analgesic-induced transformed migraine.Headache. 1998;38:534-539.

5.

Srikiatkhachorn A, Tarasub N, Govitrapong P.Effect of chronic analgesic exposure on the centralserotonin system: a possible mechanism of analgesicabuse headache. Headache. 2000;40:343-350.

6.

Pina-Garza JE, Warner JS. Analgesic-inducedheadache in a 17-month-old infant. J Child Neurol.2000;15:261.

7.

Warner JS. Post-traumatic headache: a myth?Arch Neurol. 2000;57:1778-1780.

8.

Warner JS, Fenichel GM. Chronic post-traumaticheadache often a myth? Neurology. 1996;46:915-916.

9.

Silberstein SD. Drug-induced headache. NeurolClin. 1998;16:107-123.

10.

Vazquez-Barquero A, Ibanez FJ, Herra S, et al.Isolated headache as the presenting clinical manifestationof intracranial tumors: a prospective study.Cephalalgia. 1994;14:270-272.

11.

Warner JS. Prolonged recovery from reboundheadache. Headache. 2001;41:817-822.