Medication overuse headache

From WikiProjectMed
Jump to navigation Jump to search
Medication overuse headache
Other names: Rebound headache, drug overuse headaches, drug-induced headache, medication misuse headache, painkiller headaches[1][2]
The condition may be brought on by pain medications, including acetaminophen
SymptomsWhole head pain > 15 days per month[1]
ComplicationsSide effects from medication[1]
Duration> 3 months[3]
CausesFrequent triptans, opioids, barbiturates, NSAIDs, or paracetamol use[1][3]
Risk factorsSmoking[1]
Diagnostic methodBased on symptoms after excluding other potential causes[1]
Differential diagnosisMigraines, tension headaches, cluster headaches, hemicrania[4]
TreatmentStopping the excessively used medication, starting preventative medications, counselling[1]
MedicationTopiramate, valproic acid, CGRP receptor antagonists[1]
Frequency1-2% of adults (50 to 100 million)[1]

Medication overuse headache (MOH), also known as a rebound headache, are headaches that occur as the result of frequently taking pain medication.[3] The pain may involve the whole head.[1] Onset is over months to years.[3] Other health problems may include anxiety or depression.[1] Complications may include side effects from medication.[1]

Generally it occurs in people with migraines or tension-type headaches following the use of excessive acute headache relief medications.[1] The most commonly associated medications are triptans, opioids, and barbiturates; though, it may also occur with NSAIDs or paracetamol (acetaminophen).[1][3] Other risk factors include smoking.[1] Those affected have at least 15 headache days per month.[1] Diagnosis is based on symptoms after excluding other potential causes.[1]

Treatment involves reducing or stopping the excessively used medication together with starting preventative medications.[1] Preventative medications may include topiramate, valproic acid, or CGRP receptor antagonists.[1] Counseling may also be useful.[1] With treatment, the majority of people get better.[1]

Medication overuse headache affects about 1-2% of adults (50 to 100 million people).[1] Females are more commonly affected than males.[1] The condition may represent up to 70% of cases of chronic daily headaches (CDH).[3] It was first described in 1951.[1]


MOH may occur with frequent use of many different medications, including: triptans,[5] ergotamines,[6] simple and combination analgesics,[7][8] and opioids.[9] Dietary and medicinal caffeine consumption appears to be a modest risk factor for chronic daily headache onset, regardless of headache type.[10][11]

MOH is very rare in patients without a history of recurrent headaches, and it rarely develops in patients who take analgesics for non-headache pain, like arthritis or irritable bowel syndrome. Furthermore, MOH is more probable when a family history of MOH is present, thus indicating a genetical susceptibility. It is thought that rebound headaches are caused by a neuronal re-adjustment process. Analgesic intake raises the pain threshold. Thus, lacking pain stimuli for longer times, the brain re-calibrates to experience normal stimuli as pain.[12]

The time it takes for someone to develop medication overuse headaches (MOH) after taking medication too often depends on the type of medication they are using. If someone is taking triptans (such as Sumatriptan etc), it may take about 1.7 years for them to develop MOH. If they are taking ergots (such as Ergotamine etc) , it may take about 2.7 years, and if they are taking analgesics (such as Naproxen etc), it may take about 4.8 years. So, the delay between taking medication too often and developing MOH varies based on the type of medication being used.[13]

The underlying mechanisms that lead to the development of the condition are still widely unknown and clarification of their role is hampered by a lack of experimental research or suitable animal models. Various pathophysiological abnormalities have been reported and they seem to have an important role in initiating and maintaining chronic headache (genetic disposition, receptor and enzyme physiology and regulation, psychological and behavioural factors, physical dependencies, recent functional imaging results).[citation needed]

In some cases, individuals may be genetically predisposed to developing medication overuse headache. A PET study in patients with chronic analgesic overuse showed decreased activity in the orbitofrontal cortex of the brain, which is also seen in substance abuse. This suggests that there may be an underlying neurological susceptibility to addiction in some individuals. However, more research is needed to fully understand the complex interplay of factors that contribute to the development of MOH. [13][14]

Opioids and butalbital are sometimes inappropriately used as treatment for migraine and headache and should be avoided in favor of more effective, migraine-specific treatments.[15][16] Opioid and butalbital use can worsen headaches and cause MOH.[15] When a patient fails to respond to other treatment or migraine specific treatment is unavailable, then opioids may be used.[16]

Regular use of over-the-counter drugs (OTC) such as paracetamol and NSAIDs can also be a cause.[17] OTC medication for headache should be limited to use for not more than two days weekly,[17] and it is recommended to seek medical counsel when any pain lasts more than a few days. Concurrent with MOH, overuse of acetaminophen (known as paracetamol in some countries) for treating headaches risks causing liver damage and NSAID overuse can cause gastrointestinal bleeding.[17]


Medication overuse headache is within the International Classification of Headache Disorders (ICHD) classification.[18] Over the years different diagnostic criteria have been proposed. The term MOH first appeared in the ICHD 2nd edition in 2004. It was defined as a secondary headache, with the aim of emphasizing excessive medication intake as the basis of this form of headache. The two subsequent revisions of the criteria (2005 and 2006) refined and extended the definition of the condition on the basis of both its chronicity (headache on more than 15 days per month for more than three months) and medication classes, thereby identifying the main types of MOH. In the case of ergotamine, triptans, opioids and combination medications in particular, intake on > 10 days/month for > 3 months is required, whereas simple analgesics are considered overused when they are taken on > 15 days/month for >3 months.[19]


In general, any person who has frequent headaches should be considered as a potential candidate for preventive medications instead of being encouraged to take more and more painkillers or other rebound-causing medications. Preventive medications are taken on a daily basis. Some may require preventive medications for many years; others may require them for only a relatively short period of time. Preventive medications come from many classes of medications including anticonvulsants, antidepressants, antihypertensives, and antihistamines. They include amitriptyline, valproate, topiramate, propranolol.


MOH is common and can be treated. The overused medications must be stopped for the patient's headache to resolve, though there is limited evidence to suggest this can be done without using other preventive measures.[8] Clinical data shows that the treatment of election is abrupt drugs withdrawal, followed by starting prophylactic therapy. However, the discontinuation of overused drugs may lead to the initial worsening of headaches, nausea, vomiting, sleep disturbance, anxiety, and restlessness.[8] These symptoms greatly depend on the previously overused drugs and typically last from two to ten days. They are relieved by the further intake of the overused medication, which might reinforce the continuation of overuse and noncompliance toward discontinuation. Where physical dependence or a rebound effect such as rebound headache is possible, gradual reduction of medication may be necessary.[20] It is important that the patient's physician be consulted before abruptly discontinuing certain medications as such a course of action has the potential to induce medically significant physical withdrawal symptoms. Abruptly discontinuing butalbital, for example, can actually induce seizures in some patients, although simple over the counter analgesics can safely be stopped by the patient without medical supervision. A long-acting analgesic/anti-inflammatory, such as naproxen (500 mg twice a day), can be used to ease headache during the withdrawal period.[21][22] Two months after the completion of a medication withdrawal, patients with MOH typically notice a marked reduction in headache frequency and intensity.[23]

Drug withdrawal is performed very differently within and across countries. Most physicians prefer inpatients programmes, however effective drug withdrawal may also be achieved in an outpatient setting in uncomplicated MOH patients (i.e. subjects without important co-morbidities, not overusing opioids or ergotaminics and who are at their first detoxification attempt). In the absence of evidence-based indications, in MOH patients the choice of preventive agent should be based on the primary headache type (migraine or TTH), on the drug side-effect profile, on the presence of co-morbid and co-existent conditions, on patient's preferences, and on previous therapeutic experiences.[citation needed]

Following an initial improvement of headache with the return to an episodic pattern, a relevant proportion (up to 45%) of patients relapse, reverting to the overuse of symptomatic drugs.[citation needed]

Predictors of the relapse, and that could influence treatment strategies, are considered the type of primary headache, from which MOH has evolved, and the type of drug abused (analgesics, and mostly combination of analgesics, but also drugs containing barbiturates or tranquillisers cause significantly higher relapse rates), while gender, age, duration of disease and previous intake of preventative treatment do not seem to predict relapse rate.

MOH is clearly a cause of disability and, if not adequately treated, it represents a condition of risk of possible co-morbidities associated to the excessive intake of drugs that are not devoid of side-effect. MOH can be treated through withdrawal of the overused drug(s) and by means of specific approaches that focus on the development of a close doctor-patient relationship in the post-withdrawal period.


It was first described in 1951.[1]

See also


  1. 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 1.10 1.11 1.12 1.13 1.14 1.15 1.16 1.17 1.18 1.19 1.20 1.21 1.22 1.23 1.24 Ashina, S; Terwindt, GM; Steiner, TJ; Lee, MJ; Porreca, F; Tassorelli, C; Schwedt, TJ; Jensen, RH; Diener, HC; Lipton, RB (2 February 2023). "Medication overuse headache". Nature reviews. Disease primers. 9 (1): 5. doi:10.1038/s41572-022-00415-0. PMID 36732518.
  2. "Medically unexplained symptoms". 19 October 2017. Archived from the original on 29 September 2017. Retrieved 29 March 2021.
  3. 3.0 3.1 3.2 3.3 3.4 3.5 Wakerley, Benjamin R (October 2019). "Medication-overuse headache". Practical Neurology. 19 (5): 399–403. doi:10.1136/practneurol-2018-002048. PMID 31273078.
  4. Yancey, Joseph R.; Sheridan, Richard; Koren, Kelly G. (15 April 2014). "Chronic Daily Headache: Diagnosis and Management". American Family Physician. 89 (8): 642–648. Archived from the original on 25 March 2023. Retrieved 9 August 2023.
  5. "The International Classification of Headache Disorders". The International Headache Society. Archived from the original on 16 November 2012. Retrieved 28 June 2014.
  6. "The International Classification of Headache Disorders". The International Headache Society. Archived from the original on 18 November 2012. Retrieved 28 June 2014.
  7. "The International Classification of Headache Disorders". The International Headache Society. Archived from the original on 18 November 2012. Retrieved 28 June 2014.
  8. 8.0 8.1 8.2 Chiang, Chia-Chun; Schwedt, Todd J; Wang, Shuu-Jiun; Dodick, David W (2016). "Treatment of medication-overuse headache: A systematic review". Cephalalgia. 36 (4): 371–386. doi:10.1177/0333102415593088. ISSN 0333-1024. PMID 26122645. S2CID 36144020.
  9. "The International Classification of Headache Disorders". The International Headache Society. Archived from the original on 18 November 2012. Retrieved 28 June 2014.
  10. Scher, Ann I.; Stewart, Walter F.; Lipton, Richard B. (2004). "Caffeine as a risk factor for chronic daily headache: A population-based study". Neurology. 63 (11): 2022–2027. doi:10.1212/01.WNL.0000145760.37852.ED. PMID 15596744. S2CID 25344474.
  11. Bulletin, Drug Therapeutics (2010). "Management of medication overuse headache". Drug and Therapeutics Bulletin. 340: c1305. doi:10.1136/bmj.c1305. PMID 20427444. S2CID 220110431. Archived from the original on 13 April 2018. Retrieved 11 April 2018.
  12. Saxhaug Kristoffersen, Esper; Lundqvist, Christofer (2014). "Medication-overuse headache: a review". Journal of Pain Research. 7: 367–378. doi:10.2147/JPR.S46071. PMC 4079825. PMID 25061336.
  13. 13.0 13.1 "Medication Overuse Headache: What are the Causes, Symptoms, Diagnosis, Treatment, and Prevention". Archived from the original on 2023-04-27. Retrieved 2023-04-27.
  14. Fumal, Arnaud; Laureys, Steven; Di Clemente, Laura; Boly, Mélanie; Bohotin, Valentin; Vandenheede, Michel; Coppola, Gianluca; Salmon, Eric; Kupers, Ron; Schoenen, Jean (2005-12-05). "Orbitofrontal cortex involvement in chronic analgesic-overuse headache evolving from episodic migraine". Brain. 129 (2): 543–550. doi:10.1093/brain/awh691. ISSN 1460-2156. Archived from the original on 2023-07-01. Retrieved 2023-06-09.
  15. 15.0 15.1 Consumer Reports Health Best Buy Drugs (21 August 2012), "Treating Migraine Headaches: Some Drugs should rarely be used" (PDF), Drugs for Migraine Headaches (AAN), Yonkers, New York: Consumer Reports, archived from the original on 19 December 2013, retrieved 28 October 2013
  16. 16.0 16.1 American Academy of Neurology (February 2013), "Five Things Physicians and Patients Should Question", Choosing Wisely: an initiative of the ABIM Foundation, American Academy of Neurology, archived from the original on September 1, 2013, retrieved August 1, 2013, which cites
  17. 17.0 17.1 17.2 American Headache Society (September 2013), "Five Things Physicians and Patients Should Question", Choosing Wisely: an initiative of the ABIM Foundation, American Headache Society, archived from the original on 6 December 2013, retrieved 10 December 2013, which cites
  18. "The International Headache Classification". International Headache Society. Archived from the original on 4 March 2016. Retrieved 28 June 2014.
  19. Ashina, Sait; Terwindt, Gisela M.; Steiner, Timothy J.; Lee, Mi Ji; Porreca, Frank; Tassorelli, Cristina; Schwedt, Todd J.; Jensen, Rigmor H.; Diener, Hans-Christoph; Lipton, Richard B. (2023-02-02). "Medication overuse headache". Nature Reviews Disease Primers. 9 (1): 1–20. doi:10.1038/s41572-022-00415-0. ISSN 2056-676X. Archived from the original on 2023-05-01. Retrieved 2023-06-09.
  20. de Filippis S, Salvatori E, Farinelli I, Coloprisco G, Martelletti P (2007). "Chronic daily headache and medication overuse headache: clinical read-outs and rehabilitation procedures". Clin Ter. 158 (4): 343–7. PMID 17953286.
  21. Silberstein SD, McCrory DC (2001). "Butalbital in the treatment of headache: history, pharmacology, and efficacy". Headache. 41 (10): 953–67. doi:10.1046/j.1526-4610.2001.01189.x. PMID 11903523. S2CID 27684961.
  22. Loder E, Biondi D (September 2003). "Oral phenobarbital loading: a safe and effective method of withdrawing patients with headache from butalbital compounds". Headache. 43 (8): 904–9. doi:10.1046/j.1526-4610.2003.03171.x. PMID 12940814. S2CID 36000736.
  23. Zeeberg P, Olesen J, Jensen R (June 2006). "Probable medication-overuse headache: the effect of a 2-month drug-free period". Neurology. 66 (12): 1894–8. doi:10.1212/ PMID 16707727. S2CID 23088630.

External links