The International Classification of Headache Disorders 2nd Edition


Medication-overuse headache (MOH)



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8.2 Medication-overuse headache (MOH)

Previously used terms:

Rebound headache, drug-induced headache, medication-misuse headache

Introduction


This and the following section deal with headache disorders associated with chronic substance use or exposure.

Medication-overuse headache is an interaction between a therapeutic agent used excessively and a susceptible patient. The best example is overuse of symptomatic headache drugs causing headache in the headache-prone patient.

By far the most common cause of migraine-like headache occurring on 15 days per month and of a mixed picture of migraine-like and tension-type-like headaches on 15 days per month is overuse of symptomatic migraine drugs and/or analgesics. In general, overuse is defined in terms of treatment days per month. What is crucial is that treatment occurs both frequently and regularly, ie, on several days each week. For example, if the diagnostic criterion is use on 10 days per month, this translates into 2-3 treatment days every week. Bunching of treatment days with long periods without medication intake, practised by some patients, is much less likely to cause medication-overuse headache.

Chronic tension-type headache is less often associated with medication overuse but, especially amongst patients seen in headache centres, episodic tension-type headache has commonly become a chronic headache through overuse of analgesics.

Patients with a pre-existing primary headache who develop a new type of headache or whose migraine or tension-type headache is made markedly worse during medication overuse should be given both the diagnosis of the pre-existing headache and the diagnosis of 8.2 Medication-overuse headache. Furthermore, the headache associated with medication overuse often has a peculiar pattern shifting, even within the same day, from having migraine-like characteristics to having those of tension-type headache (ie, a new type of headache).

The diagnosis of medication-overuse headache is clinically extremely important because patients rarely respond to preventative medications whilst overusing acute medications.


Diagnostic criteria:

A. Headache1 present on ≥15 days/month fulfilling criteria C and D

B. Regular overuse2 for >3 months of one or more drugs that can be taken for acute and/or symptomatic treatment of headache3

C. Headache has developed or markedly worsened during medication overuse

D. Headache resolves or reverts to its previous pattern within 2 months after discontinuation of overused medication4


Notes:

1. The headache associated with medication overuse is variable and often has a peculiar pattern with characteristics shifting, even within the same day, from migraine-like to those of tension-type headache.

2. Overuse is defined in terms of duration and treatment days per week. What is crucial is that treatment occurs both frequently and regularly, ie, on 2 or more days each week. Bunching of treatment days with long periods without medication intake, practised by some patients, is much less likely to cause medication-overuse headache and does not fulfil criterion B.

3. MOH can occur in headache-prone patients when acute headache medications are taken for other indications.

4 A period of 2 months after cessation of overuse is stipulated in which improvement (resolution of headache, or reversion to its previous pattern) must occur if the diagnosis is to be definite. Prior to cessation, or pending improvement within 2 months after cessation, the diagnosis 8.2.8 Probable medication-overuse headache should be applied. If such improvement does not then occur within 2 months, this diagnosis must be discarded.


Comments

Medication-overuse headache is an interaction between a therapeutic agent used excessively and a susceptible patient. The best example is overuse of symptomatic headache drugs causing headache in the headache-prone patient. By far the most common cause of migraine-like headache occurring on 15 days per month and of a mixed picture of migraine-like and tension-type-like headaches on 15 days per month is overuse of symptomatic migraine drugs and/or analgesics. Chronic tension-type headache is less often associated with medication overuse but, especially amongst patients seen in headache centres, episodic tension-type headache has commonly become a chronic headache through overuse of analgesics.

Patients with a pre-existing primary headache who develop a new type of headache or whose migraine or tension-type headache is made markedly worse during medication overuse should be given both the diagnosis of the pre-existing headache and the diagnosis of 8.2 Medication-overuse headache.

The diagnosis of medication-overuse headache is clinically extremely important because patients rarely respond to preventative medications whilst overusing acute medications.

8.2.1 Ergotamine-overuse headache

Diagnostic criteria:

A. Headache fulfilling criteria A, C and D for 8.2 Medication-overuse headache

B. Ergotamine intake on 10 days/month on a regular basis for >3 months


8.2.1 Ergotamine-overuse headache

Diagnostic criteria:

A. Headache present on >15 days/month with at least one of the following characteristics and fulfilling criteria C and D:

1. bilateral

2. pressing/tightening quality

3. mild or moderate intensity

B. Ergotamine intake on 10 days/month on a regular basis for 3 months

C. Headache has developed or markedly worsened during ergotamine overuse

D. Headache resolves or reverts to its previous pattern within 2 months after discontinuation of ergotamine

Comment:

Bioavailability of ergots is so variable that a minimum dose cannot be defined.

8.2.2 Triptan-overuse headache

Diagnostic criteria:

A. Headache fulfilling criteria A, C and D for 8.2 Medication-overuse headache

B. Triptan intake (any formulation) on 10 days/month on a regular basis for >3 months



  1. Headache present on >15 days/month with at least one of the following characteristics and fulfilling criteria C and D:

  1. predominantly unilateral

  2. pulsating quality

  3. moderate or severe intensity

  4. aggravated by or causing avoidance of routine physical activity (eg, walking or climbing stairs)

  5. associated with at least one of the following:

a) nausea and/or vomiting

b) photophobia and phonophobia

B. Triptan intake (any formulation) on 10 days/month on a regular basis for 3 months

C. Headache frequency has markedly increased during triptan overuse

D. Headache reverts to its previous pattern within 2 months after discontinuation of triptan

Comment:

Triptan overuse may increase migraine frequency to that of chronic migraine. Evidence suggests that this occurs sooner with triptan-overuse than with ergotamine-overuse.

8.2.3 Analgesic-overuse headache

Diagnostic criteria:

A. Headache fulfilling criteria A, C and D for 8.2 Medication-overuse headache

B. Intake of simple analgesics on 15 days/month1 on a regular basis for >3 months



  1. Headache present on >15 days/month with at least one of the following characteristics and fulfilling criteria C and D:

    1. bilateral

    2. pressing/tightening (non-pulsating) quality

    3. mild or moderate intensity

B. Intake of simple analgesics on 15 days/month1 for >3 months

C. Headache has developed or markedly worsened during analgesic overuse

D. Headache resolves or reverts to its previous pattern within 2 months after discontinuation of analgesics

Note:

1. Expert opinion rather than formal evidence suggests that use on 15 days/month rather than 10 days/month is needed to induce analgesic-overuse headache.

8.2.4 Opioid-overuse headache

Diagnostic criteria:

A. Headache fulfilling criteria A, C and D for 8.2 Medication-overuse headache

B. Opioid intake on 10 days/month on a regular basis for >3 months



  1. Headache present on >15 days/month fulfilling criteria C and D

B. Opioid intake on 10 days/month for >3 months

C. Headache develops or markedly worsens during opioid overuse

D. Headache resolves or reverts to its previous pattern within 2 months after discontinuation of opioid

Comment:

Prospective studies indicate that patients overusing opioids have the highest relapse rate after withdrawal treatment.

8.2.5 Combination medicationanalgesic-overuse headache

Diagnostic criteria:

A. Headache fulfilling criteria A, C and D for 8.2 Medication-overuse headache

B. Intake of combination analgesic medications1 on 10 days/month on a regular basis for >3 months

A. Headache present on >15 days/month with at least one of the following characteristics and fulfilling criteria C and D:

1. bilateral

2. pressing/tightening (non-pulsating) quality

3. mild or moderate intensity

B. Intake of combination medications1 on 10 days/month for >3 months

C. Headache develops or markedly worsens during combination medication overuse

D. Headache resolves or reverts to its previous pattern within 2 months after discontinuation of combination medication

Note:

1. Combination medications typically implicated are those containing simple analgesics combined with opioids, butalbital and/or caffeine

8.2.6 Medication-overuse headache attributed to combination of acute medications

Diagnostic criteria:

A. Headache fulfilling criteria A, C and D for 8.2 Medication-overuse headache

B. Intake of any combination of ergotamine, triptans, analgesics and/or opioids on 10 days/month on a regular basis for >3 months without overuse of any single class alone1


Note:

1. The specific subform(s) 8.2.1-8.2.5 should be diagnosed if criterion B is fulfilled in respect of any one or more single class(es) of these medications

8.2.6 7 Headache attributed to other medication overuse

Diagnostic criteria:

A. Headache fulfilling criteria A, C and D for 8.2 Medication-overuse headache

B. Regular overuse1 for >3 months of a medication other than those described above

A. Headache present on >15 days/month fulfilling criteria C and D

B. Regular overuse1 for >3 months of a medication other than those described above

C. Headache has developed or markedly worsened during medication overuse

D. Headache resolves or reverts to its previous pattern within 2 months after discontinuation of overused medication



Note:

1. The definition of overuse in terms of treatment days per month week is likely to vary with the nature of the medication.

8.2.7 8 Probable medication-overuse headache

Diagnostic criteria:

A. Headache fulfilling criteria A-C for any one of the subforms 8.2.1 to 8.2.6 above

B. One or other of the following:

1. overused medication has not yet been withdrawn

2. medication overuse has ceased within the last 2 months but headache has not so far resolved or reverted to its previous pattern

A. Headache fulfilling criteria A and C for 8.2 Medication-overuse headache

B. Medication overuse fulfilling criterion B for any one of the subforms 8.2.1 to 8.2.7

C. One or other of the following:

1. overused medication has not yet been withdrawn

2. medication overuse has ceased within the last 2 months but headache has not so far resolved or reverted to its previous pattern

Comments:

Codable subforms of 8.2.87 Probable medication-overuse headache are 8.2.87.1 Probable ergotamine-overuse headache, 8.2.87.2 Probable triptan-overuse headache, 8.2.87.3 Probable analgesic-overuse headache, 8.2.87.4 Probable opioid-overuse headache, 8.2.87.5 Probable combination analgesicmedication-overuse headache, 8.2.8.6 Headache probably attributed to overuse of acute medication combinations and 8.2.8.77.6 Headache probably attributed to other medication overuse.

Many patients fulfilling the criteria for 8.2.7 8 Probable medication-overuse headache also fulfil criteria for either 1.6.5 Probable chronic migraine or 2.4.3 Probable chronic tension-type headache. They should be coded for both until causation is established after withdrawal of the overused medication. Patients with 1.6.5 Probable chronic migraine should additionally be coded for the antecedent migraine subtype (usually 1.1 Migraine without aura).


8.3 Headache as an adverse event attributed to chronic medication

Diagnostic criteria:

A. Headache present on >15 days/month fulfilling criteria C and D

B. Chronic medication1 for any therapeutic indication

C. Headache develops during medication

D. Headache resolves after discontinuation of medication2



Notes:

1. The definition of dose and duration will vary with the medication.

2. Time for resolution will vary with the medication but may be months.


Comment:

Headache can be due to a direct pharmacologic effect of medication, such as vasoconstriction producing malignant hypertension and headache, or to a secondary effect such as drug-induced intracranial hypertension. The latter is a recognised complication of long-term use of anabolic steroids, amiodarone, lithium carbonate, nalidixic acid, thyroid hormone replacement, tetracycline or minocycline.

8.3.1 Exogenous hormone-induced headache

Diagnostic criteria:

  1. Headache or migraine fulfilling criteria C and D

  2. Regular use of exogenous hormones

  3. Headache or migraine develops or markedly worsens within 3 months of commencing exogenous hormones

  4. Headache or migraine resolves or reverts to its previous pattern within 3 months after total discontinuation of exogenous hormones



Comments:

Regular use of exogenous hormones, typically for contraception or hormone replacement therapy, can be associated with increase in frequency or new development of headache or migraine.

When a woman also experiences headache or migraine associated with exogenous oestrogen-withdrawal, both codes 8.3.1 Exogenous hormone-induced headache and 8.4.3 Oestrogen-withdrawal headache should be used.


8.4 Headache attributed to substance withdrawal

8.4.1 Caffeine-withdrawal headache

Diagnostic criteria:

A. Bilateral and/or pulsating headache fulfilling criteria C and D

B. Caffeine consumption of >200 mg/day for >2 weeks, which is interrupted or delayed

C. Headache develops within 24 hours after last caffeine intake and is relieved within 1 hour by 100 mg of caffeine

D. Headache resolves within 7 days after total caffeine withdrawal



8.4.2. Opioid-withdrawal headache

Diagnostic criteria:

A. Bilateral and/or pulsating headache fulfilling criteria C and D

B. Opioid intake daily for >3 months, which is interrupted

C. Headache develops within 24 hours after last opioid intake

D. Headache resolves within 7 days after total opioid withdrawal



8.4.3 Oestrogen-withdrawal headache

Diagnostic criteria:

  1. Headache or migraine fulfilling criteria C and D

  2. Daily use of exogenous oestrogen for 3 weeks, which is interrupted

  3. Headache or migraine develops within 5 days after last use of oestrogen

  4. Headache or migraine resolves within 3 days



Comment:

Oestrogen-withdrawal following cessation of a course of exogenous oestrogens (such as during the pill-free interval of combined oral contraceptives or following a course of replacement or supplementary oestrogen) can induce headache and/or migraine.

8.4.4 Headache attributed to withdrawal from chronic use of other substances

Diagnostic criteria:

A. Bilateral and/or pulsating headache fulfilling criteria C and D

B. Daily intake of a substance other than those described above for >3 months, which is interrupted

C. Headache develops in close temporal relation to withdrawal of the substance

D. Headache resolves within 3 months after withdrawal



Comment:

It has been suggested, but without sufficient evidence, that withdrawal of the following substances may cause headache: corticosteroids, tricyclic antidepressants, selective serotonin reuptake inhibitors (SSRIs), non-steroidal anti-inflammatory drugs (NSAIDs).

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8.2 Medication-overuse headache

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Diener, H.C. and P. Tfelt-Hansen (1993). Headache associated with chronic use of substances. In The headaches, (J. Olesen, P. Tfelt-Hansen, and K.M.A. Welch, eds.) pp. 721-727. Raven press LTD, New York.

Dige-Petersen, H., N.A. Lassen, J. Noer, K.H. Toennesen, and J. Olesen (1977). Subclinical ergotism. Lancet i:65-66.

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Fincham, R.W., Z. Perdue, and V.D. Dunn (1985). Bilateral focal cortical atrophy and chronic ergotamine abuse. Neurology 35:720-722.

Fisher, C.M. (1988). Analgesic rebound headache refuted. Headache 28:666.

Friedman, A.P., P. Brazil, and T.J. vonStorch (1955). Ergotamine tolerance in patients with migraine. JAMA 157:881-884.

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Horowski, R. and A. Ziegler (1988). Possible pharmacological mechanisms of chronic abuse of analgesics and other antimigraine drugs. In Drug-induced headache, (H.C. Diener and M. Wilkinson, eds. ) pp. 95-104. Springer-Verlag, Berlin.

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Lucas, R.N. and W. Falkowski (1973). Ergotamine and methysergide abuse in patients with migraine. Br J Psychiatry 122:199-203.

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MacGregor, E.A., C. Vorah, and M. Wilkinson (1990). Analgesic use: a study of treatments used by patients for migraine prior to attending the City of London migraine clinic. Headache 30:634-638.

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Mathew, N.T., R. Kurman, and F. Perez (1990). Drug induced refractory headache - clinical features and management. Headache 30:634-638.

Michultka, D.M., E.B. Blanchard, K.A. Appelbaum, J. Jaccard, and M.P. Dentinger (1989). The refractory headache patient--2. High medication consumption (analgesic rebound) headache. Behav Res Ther 27:411-420.

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Tfelt-Hansen, P. (1985). Ergotamine headache. In Updating in headache, (V. Pfaffenrath, P. Lundberg, and O. Sjaastad, eds.) pp. 169-172. Springer, Berlin.

Tfelt-Hansen, P. (1986). The effect of ergotamine on the arterial system in man. Acta Pharmacol Toxicol 59:1-29.

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Tfelt-Hansen, P., P.R. Saxena, and M.D. Ferrari (1995). Ergot alkaloids. In Handbook of clinical neurology, (F.A. DeWolff, ed.) pp. 61-67. New York: Elsevier Science.

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Vasconcellos, E., J.E. Pina-Garza, E.J. Millan, and J.S. Warner (1998). Analgesic rebound headache in children and adolescents. J Child Neurol 13:443-447.

Verhoeff, N.P., W.H. Visser, M.D. Ferrari, P.R. Saxena, and E.A. vonRoyen (1993). Dopamine D2 receptor imaging with 123-I-iodobenzamide SPECT in migraine patients abusing ergotamine: does ergotamine cross the blood brain barrier. Cephalalgia 13:325-329.

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Ziegler, D.K. (2000). Opiate and opioid use in patients with refractory headache. Cephalalgia 14:5-10.

8.3 Headache as an adverse event attributed to chronic medication

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Silberstein SD. Hormone-related headache. M Clin N Am 2001;85:1017-1035.

Silberstein SD, de Lignières B. Migraine, menopause and hormonal replacement therapy. Cephalalgia 2000;20:214-212.

8.4 Headache attributed to substance withdrawal

Abbott, P.J. (1986). Caffeine: a toxicological overview. Med J Aust 145:518-521.

Baumgartner, G.R. and R.C. Rowen (1991). Transdermal clonidine versus chlordiazepoxide in alcohol withdrawal: a randomized, controlled clinical trial. South Med J 84:312-321.

Dalessio, D.J. (1980). Wolff's headache and other head pain, Oxford University Press, Oxford.

Epstein MT, JM Hockaday, TDR Hockaday (1975). Migraine and reproductive hormones through the menstrual cycle. Lancet i:543-548.

Greden, J.F., M. Fontaine, M. Lubetsky, and K. Chamberlin (1978). Anxiety and depression associated with caffeinism among psychiatric inpatients. Am J Psychiatr 135:963-966.

Laska, E.M., A. Sunshine, F. Mueller, W.B. Elvers, C. Siegel, and A. Rubin (1984). Caffeine as an analgesic adjuvant. JAMA 251:1711-1718.

Lichten E, J Lichten, A Whitty, D Pieper (1996). The confirmation of a biochemical marker for women’s hormonal migraine : the depo-oestradiol challenge test. Headache 36: 367-71.

Raskin, N.H. and O. Appenzeller (1980). Headache, Saunders, Philadelphia.

Silverman, K., S.M. Evans, E.C. Strain, and R.R. Griffiths (1992). Withdrawal syndrome after the double-blind cessation of caffeine consumption. N Eng J Med 327:1109-1114.

Somerville B (1975). Estrogen withdrawal migraine. Neurology 25: 239-250.

vanDusseldorp, M. and M.B. Katan (1990). Headache caused by caffeine withdrawal among moderate coffee drinkers switched from ordinary to decaffeinated coffee: a 12 week double blind trial. Br Med J 300:1558-1559.

White, B.C., C.A. Lincoln, N.W. Pearcz, R. Reeb, and C. Vaida (1980). Anxiety and muscle tension as consequence of caffeine withdrawal. Science 209:1547-1548.







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