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Calculated Shard: 129 (from laksa012)

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curl -X POST \
  'http://laksa129.int.ahrefs:8124/' \
  -H 'Content-Type: text/plain' \
  -H 'X-ClickHouse-Database: crawler3' \
  -H 'Authorization: Basic YXBpOg==' \
  -d 'SELECT getAhrefsURLFromUnparsed(src_unparsed) AS found_url, ifNull(toUnixTimestamp(download_stamp), 0) AS crawl_time, ifNull(toUnixTimestamp(props_url_first_seen), 0) AS first_indexed_time, download_http_code AS http_code, src_unparsed AS src_unparsed, src_root_hash AS src_root_hash, history_drop_reason AS history_drop_reason, meta_title AS meta_title, meta_descriptions AS meta_descriptions, attrs_boilerpipe_text AS attrs_boilerpipe_text, attrs_markdown AS attrs_markdown, attrs_readable_markdown AS attrs_readable_markdown, meta_canonical AS meta_canonical FROM crawler3.page_info_local FINAL PREWHERE (src_root_hash, src_unparsed) IN ((getAhrefsRootHashFromUnparsed(getAhrefsUnparsedNoserviceFromURL(\'https://www.ncbi.nlm.nih.gov/books/NBK470171/\')), getAhrefsUnparsedNoserviceFromURL(\'https://www.ncbi.nlm.nih.gov/books/NBK470171/\'))) FORMAT JSONEachRow'

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{"found_url":"https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK470171\/","crawl_time":1771312089,"first_indexed_time":1563271838,"http_code":200,"src_unparsed":"gov,nih!nlm,ncbi,www,\/books\/NBK470171\/ s443","src_root_hash":"7295144728021232729","history_drop_reason":null,"meta_title":"Medication Overuse Headache - StatPearls - NCBI Bookshelf","meta_descriptions":["According to the International Classification of Headache Disorders, 3rd edition (ICHD-3), a medication overuse headache is a secondary chronic headache disorder. This condition is defined as headaches occurring for 15 or more days per month for 3 or more months in patients who use acute headache treatments too frequently.[1] Medication overuse headaches are believed to occur when medications intended to relieve headaches are consumed too frequently, leading to a secondary type of headache. This condition was previously called a rebound headache and is commonly observed in individuals with migraine; the excessive use of analgesics can transform episodic headaches into a chronic condition. The exact frequency of using the pain-relieving drug before developing the medication overuse headache varies and depends on the particular type of medication used. Causal agents include both simple and combination analgesics, triptans, ergot derivatives, and opioids, but potentially any painkiller can be the trigger. Patients who use simple analgesics and nonsteroidal anti-inflammatory drugs (NSAIDs) for 15 or more days, or who take combination analgesics—including ergots; barbiturates, such as butalbital; triptans; and opioids—for 10 or more days per month are considered to have a medication overuse headache. Medication overuse headaches are common in patients at risk of overusing acute medications. Individuals previously diagnosed with a primary headache disorder, particularly migraines or tension-type headaches, are at risk of developing this condition. Medication overuse headaches typically resolve once the overused medication is reduced or discontinued.[2][3][4][5][6]"],"attrs_boilerpipe_text":"Continuing Education Activity\nAccording to the International Classification of Headache Disorders, 3rd edition, a medication overuse headache is a secondary chronic headache disorder. This condition is defined as headaches occurring for 15 or more days per month for 3 or more months in patients taking acute headache treatments too frequently. Medication overuse headaches are believed to occur when medications intended to relieve headaches are consumed frequently. Causal agents are varied and can include agents such as nonsteroidal anti-inflammatory drugs, triptans, ergot derivatives, and opioids, although any analgesic can potentially trigger the medication overuse headache. This activity describes issues associated with the overuse of medications intended to relieve headaches and the evaluation and management of medication overuse headaches, highlighting the role of the interprofessional team in managing headaches.\nObjectives:\nIdentify the epidemiology of medication overuse headaches.\nAssess the pathophysiology of medication overuse headaches.\nDevelop the various treatment options for managing medication overuse headaches.\nImplement interprofessional team strategies for improving care coordination and communication to advance the prevention and management of medication overuse headaches and improve patient outcomes.\nAccess free multiple choice questions on this topic.\nIntroduction\nAccording to the International Classification of Headache Disorders, 3rd edition (ICHD-3), a medication overuse headache is a secondary chronic headache disorder. This condition is defined as headaches occurring for 15 or more days per month for 3 or more months in patients who use acute headache treatments too frequently.\n[1]\nMedication overuse headaches are believed to occur when medications intended to relieve headaches are consumed too frequently, leading to a secondary type of headache. This condition was previously called a rebound headache and is commonly observed in individuals with migraine; the excessive use of analgesics can transform episodic headaches into a chronic condition. The exact frequency of using the pain-relieving drug before developing the medication overuse headache varies and depends on the particular type of medication used. Causal agents include both simple and combination analgesics, triptans, ergot derivatives, and opioids, but potentially any painkiller can be the trigger. Patients who use simple analgesics and nonsteroidal anti-inflammatory drugs (NSAIDs) for 15 or more days, or who take combination analgesics—including ergots; barbiturates, such as butalbital; triptans; and opioids—for 10 or more days per month are considered to have a medication overuse headache. Medication overuse headaches are common in patients at risk of overusing acute medications. Individuals previously diagnosed with a primary headache disorder, particularly migraines or tension-type headaches, are at risk of developing this condition. Medication overuse headaches typically resolve once the overused medication is reduced or discontinued.\n[2]\n[3]\n[4]\n[5]\n[6]\nEtiology\nTo diagnose medication overuse headaches according to the latest ICHD-3 criteria, the following three conditions must be fulfilled:\nA headache must occur 15 or more days per month in patients with a previously diagnosed headache disorder.\nA patient must have misused the acute headache medication for 3 or more months.\nA headache is not attributable to another ICHD-3 headache condition.\nMedication overuse headaches are believed to occur when patients frequently use acute headache medications at the following rates—15 or more days per month for simple analgesics, such as acetaminophen and NSAIDs, and 10 or more days per month for ergotamine, triptans, opioids, or combination analgesics, such as butalbital, acetaminophen, or caffeine.\n[7]\n[8]\nThe ICHD-3 states that when a combination of different headache medications is used, their combined frequency can lead to a medication overuse headache, even when the individual drugs are not overused separately.\nThe most common group of patients with medication overuse headaches are those with chronic migraine, who account for about two-thirds of patients with medication overuse headaches.\nPatients with headaches respond to acute medications differently. The use of an inappropriate headache abortive medication or less effective medication can increase the frequency of medication consumption and lead to medication overuse headaches. For example, due to the differences in efficacy between acetaminophen 1000 mg (NNT=12) and ibuprofen 400 mg (NNT=7.2), a patient using acetaminophen typically requires more frequent dosages to manage their headache compared to those using ibuprofen. The timing of acute headache treatment also affects the development of medication overuse headaches. Patients start medications for acute headaches, especially migraine medications, too late, which reduces their effectiveness. This underuse of both acute and preventive medications has been shown to contribute to the progression of migraine and subsequent medication overuse headaches.\n[9]\nEpidemiology\nMedication overuse headaches are considered one of the more prevalent neurological disorders. The 2015 Global Burden of Disease study estimated its prevalence at 1% worldwide, affecting approximately 58.5 million people, which is lower compared to that of migraine and tension-type headaches. However, the same study ranked medication overuse headaches among the 20 most debilitating diseases.\nMedication overuse headaches occur relatively commonly in patients with chronic migraines, with about 32% of individuals in this group experiencing medication overuse headaches. Medication overuse headaches are believed to be more common in women, with a male-to-female ratio ranging from 2:1 to 5:1, and in those with low socioeconomic status.\n[10]\nPathophysiology\nThe exact mechanism of medication overuse headaches is unclear. However, it is hypothesized that medication overuse headaches result from the depletion of 5-HT due to the overuse of headache-abortive medications. This depletion leads to neuronal hyperexcitability in the cerebral cortex, which may result in cortical spreading depression, and the trigeminal system, which produces peripheral and central sensitization. The decrease in 5-HT levels leads to an increased release of calcitonin gene-related peptide from the trigeminal ganglia, which is involved in the subsequent sensitization of nociceptive trigeminal neurons.\n[11]\nOther studies have shown structural and functional brain changes in patients with medication overuse headaches. Morphometric magnetic resonance imaging has found increased gray matter volume in regions such as the midbrain, thalamus, and striatum. The midbrain gray matter volume changes resolved after removing the offending medication. The orbitofrontal cortical gray matter volume is lower in patients with medication overuse headaches, and a poor treatment response was observed.\n[12]\nPET scans of patients with medication overuse headaches reveal significant metabolic changes in various brain structures, most of which reverse upon the withdrawal of analgesic medication, except for persistent hypometabolism observed in the orbitofrontal area. This area is known to be involved in drug dependence and is hypothesized to be a risk factor for subsequent relapse in analgesic overuse and recurrent medication overuse headaches.\n[13]\n[14]\n[13]\nHistory and Physical\nClinical presentation of medication overuse headaches varies among patients and may even change over time in the same individual. Patients may experience an increase in the frequency of a pre-existing headache or the development of a new type of headache. Since no specific tests exist for diagnosing this condition, the diagnosis relies on evaluating headache frequency, quantity, and the type and frequency of acute medication use.\n[15]\nAlthough pain location and quality are nonspecific in medication overuse headaches, certain general features are commonly observed in affected patients, including:\nThe headaches are typically episodic.\nFrequent acute medication consumption depends on the type of abortive medication used. Generally, the threshold for developing medication overuse headaches is 15 or more days for acetaminophen and NSAIDs and 10 or more days for triptans, ergots, opioids, combination analgesics, and multiple drug classes.\n[16]\nNeck pain is common and often mistaken for a cervicogenic headache, which in turn tends to be resistant to cervicalgia-appropriate treatments.\nTypically occurs in the morning, presumed related to withdrawal occurring during sleep.\nPoor sleep quality.\nAutonomic symptoms, such as nasal congestion, rhinorrhea, and gastrointestinal disturbance, are more frequent with overused opioids.\nComorbid anxiety and depression.\nAll headache treatments are generally less effective in cases of medication overuse headaches; their efficacy improves after medication withdrawal.\nEvaluation\nThere are currently no specific biomarkers or studies to differentiate or confirm medication overuse headaches. The diagnosis is entirely clinical and requires careful attention, as overlooking this condition can lead to its progression and worsening over time.\nTreatment \/ Management\nEducation is the most crucial first step for patients with medication overuse headaches. Patients must understand and be aware of the headache issues related to their symptoms and misuse of headache remedies. Mindfulness has been shown to be an effective treatment strategy.\n[17]\nIn addition to education, the standard treatment of medication overuse headaches involves weaning the patient off the overused acute headache medication while simultaneously focusing on preventative treatment. Several studies show that complete discontinuation of overused acute medication yields the best outcomes compared to continuing the same acute medication with restricted frequency. Patients can be prescribed a new acute medication from a different class. Discontinuation can be achieved either abruptly (cold turkey) or gradually over several weeks. Preventative treatment can include prophylactic medication or nonpharmaceutical treatments, such as cognitive behavioral therapy, biofeedback, relaxation training, and lifestyle modification with trigger avoidance.\n[18]\n[19]\n[20]\nEducating patients and their families about the importance of limiting acute medication use is vital in preventing medication overuse headaches. Initial worsening of a headache within the first few days of weaning is relatively common. Withdrawal symptoms are believed to last up to 10 days, then eventually followed by improvement in medication overuse headaches.\n[14]\nWeaning patients off medication overuse headache-related medication can be done in an outpatient or an inpatient setting. Most cases can be managed in the outpatient setting, mainly through educating patients to cut down on their acute medication use. Addressing and treating comorbid psychiatric conditions, especially anxiety and depression, which are often associated with medication overuse headaches, are crucial. However, without enhancing the boosting effects, anxiolytic medication may contribute to the persistence of headaches.\nFollowing successful weaning, about 50% of patients relapse after 5 years; thus, it is essential to have the patient follow-up regularly. Once the patient's medication overuse headache has resolved, tapering them off the preventative medication may be considered. There are no specific guidelines, but some clinicians suggest tapering prophylactic medications after 1 year.\n[21]\n[22]\nDifferential Diagnosis\nA medication overuse headache occurs in patients with an episodic primary headache; thus, chronic versions of an episodic headache are one of the main differentials. The most common differential diagnosis of medication overuse headache is chronic migraine. Secondary headaches should be ruled out with the guidance of the patient's clinical presentation and the aid of all the necessary tests, especially when the features of the original episodic headache are different from their chronic counterparts.\n[23]\n[24]\nPrognosis\nA tailored regime yields excellent long-term results; however, the estimated relapse rate is about 30% within 6 months and 50% following a 5-year period.\n[25]\nComplications\nComplications associated with medication overuse headaches include additional symptoms linked to more severe and chronic forms of primary headache disorders. These symptoms include nausea, anxiety, irritability, asthenia, restlessness, difficulty concentrating, problems with memory, and depression.\n[26]\nDeterrence and Patient Education\nEducation plays a crucial role in treating medication overuse headaches. Patients must understand the underlying causes of their headaches to adhere to changes in their medication regimen, which typically involves restricting their medication use. Depending on the drug used, patients may need to either discontinue the drug immediately or gradually taper the dose.\nPearls and Other Issues\nHealthcare professionals contend that frequent use of acute headache medications may indicate poorly controlled headaches and not necessarily the cause. This idea stems from evidence that not all patients improve when they stop taking headache-relieving medications. Instead of primarily blaming analgesic medication overuse as the reason for the increase in headache frequency, clinicians must be cautious in treating these patients and not overlook those in whom headaches are simply poorly controlled. Some studies suggested that other substances, such as the regular use of tranquilizers or other recreational substances abused in the general population, should be considered in conjunction with analgesics.\nEnhancing Healthcare Team Outcomes\nThe diagnosis and management of medication overuse headaches are complex and best performed by an interprofessional team that includes clinicians, specialists, nursing staff, and pharmacists. Educating the patient and their family on the importance of limiting acute medication use is vital in preventing medication overuse headaches. The underlying psychiatric condition must be addressed, and a referral to a mental health professional can be helpful. All interprofessional team members are responsible for contributing from their areas of expertise, documenting any change in patient status, and communicating their observations with other team members as appropriate so therapeutic interventions can occur if necessary.\nFollowing successful weaning, about 50% of the patients relapse after 5 years, so regular follow-up is crucial. Once the patient's medication overuse headache has resolved, tapering them off the preventative medication may be considered. There are no specific guidelines, but some professionals suggest tapering prophylactic medication after 1 year. \nReferences\n1.\nHeadache Classification Committee of the International Headache Society (IHS) The International Classification of Headache Disorders, 3rd edition.\nCephalalgia.\n2018 Jan;\n38\n(1):1-211.\n[\nPubMed\n: 29368949\n]\n2.\nLimmer AL, Holland LC, Loftus BD. Zonisamide for Cluster Headache Prophylaxis: A Case Series.\nHeadache.\n2019 Jun;\n59\n(6):924-929.\n[\nPubMed\n: 31038740\n]\n3.\nMose LS, Pedersen SS, Jensen RH, Gram B. Personality traits in migraine and medication-overuse headache: A comparative study.\nActa Neurol Scand.\n2019 Aug;\n140\n(2):116-122.\n[\nPubMed\n: 31038726\n]\n4.\nYoung NP, Philpot LM, Vierkant RA, Rosedahl JK, Upadhyaya SG, Harris A, Ebbert JO. Episodic and Chronic Migraine in Primary Care.\nHeadache.\n2019 Jul;\n59\n(7):1042-1051.\n[\nPMC free article\n: PMC6625910\n] [\nPubMed\n: 31032913\n]\n5.\nSandoe CH, Lay C. Secondary Headaches During Pregnancy: When to Worry.\nCurr Neurol Neurosci Rep.\n2019 Apr 22;\n19\n(6):27.\n[\nPubMed\n: 31011857\n]\n6.\nMicieli A, Kingston W. An Approach to Identifying Headache Patients That Require Neuroimaging.\nFront Public Health.\n2019;\n7\n:52.\n[\nPMC free article\n: PMC6428716\n] [\nPubMed\n: 30931292\n]\n7.\nGrazzi L, D'Amico D. Chronic migraine and medication overuse: which strategy for a complex scenario.\nNeurol Sci.\n2019 May;\n40\n(Suppl 1):175-176.\n[\nPubMed\n: 30906961\n]\n8.\nTurner DP, Lebowitz AD, Chtay I, Houle TT. Headache Triggers as Surprise.\nHeadache.\n2019 Apr;\n59\n(4):495-508.\n[\nPMC free article\n: PMC6521840\n] [\nPubMed\n: 30919414\n]\n9.\nRattanawong W, Rapoport A, Srikiatkhachorn A. Medication \"underuse\" headache.\nCephalalgia.\n2024 Apr;\n44\n(4):3331024241245658.\n[\nPubMed\n: 38613233\n]\n10.\nKulkarni GB, Mathew T, Mailankody P. Medication Overuse Headache.\nNeurol India.\n2021 Mar-Apr;\n69\n(Supplement):S76-S82.\n[\nPubMed\n: 34003151\n]\n11.\nPrakash S, Patel H, Shah CS. Medication-overuse headache overlapping with serotonin syndrome.\nBMJ Case Rep.\n2024 Jan 04;\n17\n(1)\n[\nPMC free article\n: PMC10773342\n] [\nPubMed\n: 38176752\n]\n12.\nRiederer F, Gantenbein AR, Marti M, Luechinger R, Kollias S, Sándor PS. Decrease of gray matter volume in the midbrain is associated with treatment response in medication-overuse headache: possible influence of orbitofrontal cortex.\nJ Neurosci.\n2013 Sep 25;\n33\n(39):15343-9.\n[\nPMC free article\n: PMC6618461\n] [\nPubMed\n: 24068801\n]\n13.\nDripps IJ, Bertels Z, Moye LS, Tipton AF, Siegersma K, Baca SM, Kieffer BL, Pradhan AA. Forebrain delta opioid receptors regulate the response of delta agonist in models of migraine and opioid-induced hyperalgesia.\nSci Rep.\n2020 Oct 19;\n10\n(1):17629.\n[\nPMC free article\n: PMC7573615\n] [\nPubMed\n: 33077757\n]\n14.\nSebastianelli G, Casillo F, Abagnale C, Di Renzo A, Ziccardi L, Parisi V, Di Lorenzo C, Serrao M, Coppola G. Neurophysiological Effects of Withdrawal from Acute Overused Medications in Chronic Migraine with Medication-Overuse Headache.\nJ Clin Med.\n2024 Dec 09;\n13\n(23)\n[\nPMC free article\n: PMC11642649\n] [\nPubMed\n: 39685947\n]\n15.\nScher AI, Rizzoli PB, Loder EW. Medication overuse headache: An entrenched idea in need of scrutiny.\nNeurology.\n2017 Sep 19;\n89\n(12):1296-1304.\n[\nPubMed\n: 28821684\n]\n16.\nGosalia H, Moreno-Ajona D, Goadsby PJ. Medication-overuse headache: a narrative review.\nJ Headache Pain.\n2024 May 31;\n25\n(1):89.\n[\nPMC free article\n: PMC11140994\n] [\nPubMed\n: 38816828\n]\n17.\nWells RE, O'Connell N, Pierce CR, Estave P, Penzien DB, Loder E, Zeidan F, Houle TT. Effectiveness of Mindfulness Meditation vs Headache Education for Adults With Migraine: A Randomized Clinical Trial.\nJAMA Intern Med.\n2021 Mar 01;\n181\n(3):317-328.\n[\nPMC free article\n: PMC7737157\n] [\nPubMed\n: 33315046\n]\n18.\nFerini-Strambi L, Galbiati A, Combi R. Sleep disorder-related headaches.\nNeurol Sci.\n2019 May;\n40\n(Suppl 1):107-113.\n[\nPubMed\n: 30906963\n]\n19.\nBarmherzig R, Kingston W. Occipital Neuralgia and Cervicogenic Headache: Diagnosis and Management.\nCurr Neurol Neurosci Rep.\n2019 Mar 19;\n19\n(5):20.\n[\nPubMed\n: 30888540\n]\n20.\nRussell MB. Epidemiology and management of medication-overuse headache in the general population.\nNeurol Sci.\n2019 May;\n40\n(Suppl 1):23-26.\n[\nPubMed\n: 30887240\n]\n21.\nArca KN, Halker Singh RB. The Hypertensive Headache: a Review.\nCurr Pain Headache Rep.\n2019 Mar 14;\n23\n(5):30.\n[\nPubMed\n: 30874912\n]\n22.\nBottiroli S, Galli F, Viana M, De Icco R, Bitetto V, Allena M, Pazzi S, Sances G, Tassorelli C. Negative Short-Term Outcome of Detoxification Therapy in Chronic Migraine With Medication Overuse Headache: Role for Early Life Traumatic Experiences and Recent Stressful Events.\nFront Neurol.\n2019;\n10\n:173.\n[\nPMC free article\n: PMC6416203\n] [\nPubMed\n: 30899242\n]\n23.\nSaengjaroentham C, Strother LC, Dripps I, Sultan Jabir MR, Pradhan A, Goadsby PJ, Holland PR. Differential medication overuse risk of novel anti-migraine therapeutics.\nBrain.\n2020 Sep 01;\n143\n(9):2681-2688.\n[\nPMC free article\n: PMC7523700\n] [\nPubMed\n: 32810212\n]\n24.\nLucas C, Diener HC. The dependence scale: an easy tool to detect chronic daily headache with medication overuse?\nJ Neurol Neurosurg Psychiatry.\n2009 Jul;\n80\n(7):704.\n[\nPubMed\n: 19531683\n]\n25.\nMunksgaard SB, Madsen SK, Wienecke T. Treatment of medication overuse headache-A review.\nActa Neurol Scand.\n2019 May;\n139\n(5):405-414.\n[\nPubMed\n: 30710346\n]\n26.\nDodick D, Freitag F. Evidence-based understanding of medication-overuse headache: clinical implications.\nHeadache.\n2006 Nov;\n46 Suppl 4\n:S202-11.\n[\nPubMed\n: 17078852\n]\nDisclosure:\nDmitri Aleksenko declares no relevant financial relationships with ineligible companies.\nDisclosure:\nForshing Lui declares no relevant financial relationships with ineligible companies.\nDisclosure:\nJuan Carlos Sánchez-Manso declares no relevant financial relationships with ineligible companies.","attrs_markdown":"**Warning:** The NCBI web site requires JavaScript to function. 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A service of the National Library of Medicine, National Institutes of Health.\n\nStatPearls \\[Internet\\]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-.\n\n[![Cover of StatPearls](https:\/\/www.ncbi.nlm.nih.gov\/corehtml\/pmc\/pmcgifs\/bookshelf\/thumbs\/th-statpearls-lrg.png)](https:\/\/www.ncbi.nlm.nih.gov\/books\/n\/statpearls\/ \"Table of Contents Page\")\n\n## StatPearls \\[Internet\\].\n[Show details](https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK470171\/#__NBK470171_dtls__)\n\nTreasure Island (FL): [StatPearls Publishing](https:\/\/www.statpearls.com\/); 2025 Jan-.\n\n# Medication Overuse Headache\nDmitri Aleksenko; Forshing Lui; Juan Carlos Sánchez-Manso.\n\n[Author Information and Affiliations](https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK470171\/#__NBK470171_ai__)\n\n#### Authors\nDmitri Aleksenko1; Forshing Lui2; Juan Carlos Sánchez-Manso3.\n\n#### Affiliations\n1 Louisiana State University HSC\n\n2 CA Northstate Uni, College of Med\n\n3 Hospital Nuestra Señora del Rosario\n\nLast Update: January 19, 2025.\n\n## Continuing Education Activity\nAccording to the International Classification of Headache Disorders, 3rd edition, a medication overuse headache is a secondary chronic headache disorder. This condition is defined as headaches occurring for 15 or more days per month for 3 or more months in patients taking acute headache treatments too frequently. Medication overuse headaches are believed to occur when medications intended to relieve headaches are consumed frequently. Causal agents are varied and can include agents such as nonsteroidal anti-inflammatory drugs, triptans, ergot derivatives, and opioids, although any analgesic can potentially trigger the medication overuse headache. This activity describes issues associated with the overuse of medications intended to relieve headaches and the evaluation and management of medication overuse headaches, highlighting the role of the interprofessional team in managing headaches.\n\n**Objectives:**\n\n- Identify the epidemiology of medication overuse headaches.\n- Assess the pathophysiology of medication overuse headaches.\n- Develop the various treatment options for managing medication overuse headaches.\n- Implement interprofessional team strategies for improving care coordination and communication to advance the prevention and management of medication overuse headaches and improve patient outcomes.\n\n[Access free multiple choice questions on this topic.](https:\/\/www.statpearls.com\/account\/trialuserreg\/?articleid=24890&utm_source=pubmed&utm_campaign=reviews&utm_content=24890)\n\n## Introduction\nAccording to the International Classification of Headache Disorders, 3rd edition (ICHD-3), a medication overuse headache is a secondary chronic headache disorder. This condition is defined as headaches occurring for 15 or more days per month for 3 or more months in patients who use acute headache treatments too frequently.[\\[1\\]](https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK470171\/#article-24890.r1) Medication overuse headaches are believed to occur when medications intended to relieve headaches are consumed too frequently, leading to a secondary type of headache. This condition was previously called a rebound headache and is commonly observed in individuals with migraine; the excessive use of analgesics can transform episodic headaches into a chronic condition. The exact frequency of using the pain-relieving drug before developing the medication overuse headache varies and depends on the particular type of medication used. Causal agents include both simple and combination analgesics, triptans, ergot derivatives, and opioids, but potentially any painkiller can be the trigger. Patients who use simple analgesics and nonsteroidal anti-inflammatory drugs (NSAIDs) for 15 or more days, or who take combination analgesics—including ergots; barbiturates, such as butalbital; triptans; and opioids—for 10 or more days per month are considered to have a medication overuse headache. Medication overuse headaches are common in patients at risk of overusing acute medications. Individuals previously diagnosed with a primary headache disorder, particularly migraines or tension-type headaches, are at risk of developing this condition. Medication overuse headaches typically resolve once the overused medication is reduced or discontinued.[\\[2\\]](https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK470171\/#article-24890.r2)[\\[3\\]](https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK470171\/#article-24890.r3)[\\[4\\]](https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK470171\/#article-24890.r4)[\\[5\\]](https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK470171\/#article-24890.r5)[\\[6\\]](https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK470171\/#article-24890.r6)\n\n## Etiology\nTo diagnose medication overuse headaches according to the latest ICHD-3 criteria, the following three conditions must be fulfilled:\n\n- A headache must occur 15 or more days per month in patients with a previously diagnosed headache disorder.\n- A patient must have misused the acute headache medication for 3 or more months.\n- A headache is not attributable to another ICHD-3 headache condition.\n\nMedication overuse headaches are believed to occur when patients frequently use acute headache medications at the following rates—15 or more days per month for simple analgesics, such as acetaminophen and NSAIDs, and 10 or more days per month for ergotamine, triptans, opioids, or combination analgesics, such as butalbital, acetaminophen, or caffeine.[\\[7\\]](https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK470171\/#article-24890.r7)[\\[8\\]](https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK470171\/#article-24890.r8)\n\nThe ICHD-3 states that when a combination of different headache medications is used, their combined frequency can lead to a medication overuse headache, even when the individual drugs are not overused separately.\n\nThe most common group of patients with medication overuse headaches are those with chronic migraine, who account for about two-thirds of patients with medication overuse headaches.\n\nPatients with headaches respond to acute medications differently. The use of an inappropriate headache abortive medication or less effective medication can increase the frequency of medication consumption and lead to medication overuse headaches. For example, due to the differences in efficacy between acetaminophen 1000 mg (NNT=12) and ibuprofen 400 mg (NNT=7.2), a patient using acetaminophen typically requires more frequent dosages to manage their headache compared to those using ibuprofen. The timing of acute headache treatment also affects the development of medication overuse headaches. Patients start medications for acute headaches, especially migraine medications, too late, which reduces their effectiveness. This underuse of both acute and preventive medications has been shown to contribute to the progression of migraine and subsequent medication overuse headaches.[\\[9\\]](https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK470171\/#article-24890.r9)\n\n## Epidemiology\nMedication overuse headaches are considered one of the more prevalent neurological disorders. The 2015 Global Burden of Disease study estimated its prevalence at 1% worldwide, affecting approximately 58.5 million people, which is lower compared to that of migraine and tension-type headaches. However, the same study ranked medication overuse headaches among the 20 most debilitating diseases.\n\nMedication overuse headaches occur relatively commonly in patients with chronic migraines, with about 32% of individuals in this group experiencing medication overuse headaches. Medication overuse headaches are believed to be more common in women, with a male-to-female ratio ranging from 2:1 to 5:1, and in those with low socioeconomic status.[\\[10\\]](https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK470171\/#article-24890.r10)\n\n## Pathophysiology\nThe exact mechanism of medication overuse headaches is unclear. However, it is hypothesized that medication overuse headaches result from the depletion of 5-HT due to the overuse of headache-abortive medications. This depletion leads to neuronal hyperexcitability in the cerebral cortex, which may result in cortical spreading depression, and the trigeminal system, which produces peripheral and central sensitization. The decrease in 5-HT levels leads to an increased release of calcitonin gene-related peptide from the trigeminal ganglia, which is involved in the subsequent sensitization of nociceptive trigeminal neurons.[\\[11\\]](https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK470171\/#article-24890.r11)\n\nOther studies have shown structural and functional brain changes in patients with medication overuse headaches. Morphometric magnetic resonance imaging has found increased gray matter volume in regions such as the midbrain, thalamus, and striatum. The midbrain gray matter volume changes resolved after removing the offending medication. The orbitofrontal cortical gray matter volume is lower in patients with medication overuse headaches, and a poor treatment response was observed.[\\[12\\]](https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK470171\/#article-24890.r12) PET scans of patients with medication overuse headaches reveal significant metabolic changes in various brain structures, most of which reverse upon the withdrawal of analgesic medication, except for persistent hypometabolism observed in the orbitofrontal area. This area is known to be involved in drug dependence and is hypothesized to be a risk factor for subsequent relapse in analgesic overuse and recurrent medication overuse headaches.[\\[13\\]](https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK470171\/#article-24890.r13)[\\[14\\]](https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK470171\/#article-24890.r14)[\\[13\\]](https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK470171\/#article-24890.r13)\n\n## History and Physical\nClinical presentation of medication overuse headaches varies among patients and may even change over time in the same individual. Patients may experience an increase in the frequency of a pre-existing headache or the development of a new type of headache. Since no specific tests exist for diagnosing this condition, the diagnosis relies on evaluating headache frequency, quantity, and the type and frequency of acute medication use.[\\[15\\]](https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK470171\/#article-24890.r15)\n\nAlthough pain location and quality are nonspecific in medication overuse headaches, certain general features are commonly observed in affected patients, including:\n\n- The headaches are typically episodic.\n- Frequent acute medication consumption depends on the type of abortive medication used. Generally, the threshold for developing medication overuse headaches is 15 or more days for acetaminophen and NSAIDs and 10 or more days for triptans, ergots, opioids, combination analgesics, and multiple drug classes.[\\[16\\]](https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK470171\/#article-24890.r16)\n- Neck pain is common and often mistaken for a cervicogenic headache, which in turn tends to be resistant to cervicalgia-appropriate treatments.\n- Typically occurs in the morning, presumed related to withdrawal occurring during sleep.\n- Poor sleep quality.\n- Autonomic symptoms, such as nasal congestion, rhinorrhea, and gastrointestinal disturbance, are more frequent with overused opioids.\n- Comorbid anxiety and depression.\n- All headache treatments are generally less effective in cases of medication overuse headaches; their efficacy improves after medication withdrawal.\n\n## Evaluation\nThere are currently no specific biomarkers or studies to differentiate or confirm medication overuse headaches. The diagnosis is entirely clinical and requires careful attention, as overlooking this condition can lead to its progression and worsening over time.\n\n## Treatment \/ Management\nEducation is the most crucial first step for patients with medication overuse headaches. Patients must understand and be aware of the headache issues related to their symptoms and misuse of headache remedies. Mindfulness has been shown to be an effective treatment strategy.[\\[17\\]](https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK470171\/#article-24890.r17)\n\nIn addition to education, the standard treatment of medication overuse headaches involves weaning the patient off the overused acute headache medication while simultaneously focusing on preventative treatment. Several studies show that complete discontinuation of overused acute medication yields the best outcomes compared to continuing the same acute medication with restricted frequency. Patients can be prescribed a new acute medication from a different class. Discontinuation can be achieved either abruptly (cold turkey) or gradually over several weeks. Preventative treatment can include prophylactic medication or nonpharmaceutical treatments, such as cognitive behavioral therapy, biofeedback, relaxation training, and lifestyle modification with trigger avoidance.[\\[18\\]](https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK470171\/#article-24890.r18)[\\[19\\]](https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK470171\/#article-24890.r19)[\\[20\\]](https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK470171\/#article-24890.r20)\n\nEducating patients and their families about the importance of limiting acute medication use is vital in preventing medication overuse headaches. Initial worsening of a headache within the first few days of weaning is relatively common. Withdrawal symptoms are believed to last up to 10 days, then eventually followed by improvement in medication overuse headaches.[\\[14\\]](https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK470171\/#article-24890.r14) Weaning patients off medication overuse headache-related medication can be done in an outpatient or an inpatient setting. Most cases can be managed in the outpatient setting, mainly through educating patients to cut down on their acute medication use. Addressing and treating comorbid psychiatric conditions, especially anxiety and depression, which are often associated with medication overuse headaches, are crucial. However, without enhancing the boosting effects, anxiolytic medication may contribute to the persistence of headaches.\n\nFollowing successful weaning, about 50% of patients relapse after 5 years; thus, it is essential to have the patient follow-up regularly. Once the patient's medication overuse headache has resolved, tapering them off the preventative medication may be considered. There are no specific guidelines, but some clinicians suggest tapering prophylactic medications after 1 year.[\\[21\\]](https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK470171\/#article-24890.r21)[\\[22\\]](https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK470171\/#article-24890.r22)\n\n## Differential Diagnosis\nA medication overuse headache occurs in patients with an episodic primary headache; thus, chronic versions of an episodic headache are one of the main differentials. The most common differential diagnosis of medication overuse headache is chronic migraine. Secondary headaches should be ruled out with the guidance of the patient's clinical presentation and the aid of all the necessary tests, especially when the features of the original episodic headache are different from their chronic counterparts.[\\[23\\]](https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK470171\/#article-24890.r23)[\\[24\\]](https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK470171\/#article-24890.r24)\n\n## Prognosis\nA tailored regime yields excellent long-term results; however, the estimated relapse rate is about 30% within 6 months and 50% following a 5-year period.[\\[25\\]](https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK470171\/#article-24890.r25)\n\n## Complications\nComplications associated with medication overuse headaches include additional symptoms linked to more severe and chronic forms of primary headache disorders. These symptoms include nausea, anxiety, irritability, asthenia, restlessness, difficulty concentrating, problems with memory, and depression.[\\[26\\]](https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK470171\/#article-24890.r26)\n\n## Deterrence and Patient Education\nEducation plays a crucial role in treating medication overuse headaches. Patients must understand the underlying causes of their headaches to adhere to changes in their medication regimen, which typically involves restricting their medication use. Depending on the drug used, patients may need to either discontinue the drug immediately or gradually taper the dose.\n\n## Pearls and Other Issues\nHealthcare professionals contend that frequent use of acute headache medications may indicate poorly controlled headaches and not necessarily the cause. This idea stems from evidence that not all patients improve when they stop taking headache-relieving medications. Instead of primarily blaming analgesic medication overuse as the reason for the increase in headache frequency, clinicians must be cautious in treating these patients and not overlook those in whom headaches are simply poorly controlled. Some studies suggested that other substances, such as the regular use of tranquilizers or other recreational substances abused in the general population, should be considered in conjunction with analgesics.\n\n## Enhancing Healthcare Team Outcomes\nThe diagnosis and management of medication overuse headaches are complex and best performed by an interprofessional team that includes clinicians, specialists, nursing staff, and pharmacists. Educating the patient and their family on the importance of limiting acute medication use is vital in preventing medication overuse headaches. The underlying psychiatric condition must be addressed, and a referral to a mental health professional can be helpful. All interprofessional team members are responsible for contributing from their areas of expertise, documenting any change in patient status, and communicating their observations with other team members as appropriate so therapeutic interventions can occur if necessary.\n\nFollowing successful weaning, about 50% of the patients relapse after 5 years, so regular follow-up is crucial. Once the patient's medication overuse headache has resolved, tapering them off the preventative medication may be considered. There are no specific guidelines, but some professionals suggest tapering prophylactic medication after 1 year.\n\n## Review Questions\n- [Access free multiple choice questions on this topic.](https:\/\/www.statpearls.com\/account\/trialuserreg\/?articleid=24890&utm_source=pubmed&utm_campaign=reviews&utm_content=24890)\n- [Click here for a simplified version.](https:\/\/mdsearchlight.com\/migraine-headaches\/headache-from-medication-overuse\/?utm_source=pubmedlink&utm_campaign=MDS&utm_content=24890)\n- [Comment on this article.](https:\/\/www.statpearls.com\/articlelibrary\/commentarticle\/24890\/?utm_source=pubmed&utm_campaign=comments&utm_content=24890)\n\n## References\n1\\.\n\nHeadache Classification Committee of the International Headache Society (IHS) The International Classification of Headache Disorders, 3rd edition. Cephalalgia. 2018 Jan;38(1):1-211. \\[[PubMed: 29368949](https:\/\/pubmed.ncbi.nlm.nih.gov\/29368949)\\]\n\n2\\.\n\nLimmer AL, Holland LC, Loftus BD. 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Headache. 2006 Nov;46 Suppl 4:S202-11. \\[[PubMed: 17078852](https:\/\/pubmed.ncbi.nlm.nih.gov\/17078852)\\]\n\n**Disclosure:** Dmitri Aleksenko declares no relevant financial relationships with ineligible companies.\n\n**Disclosure:** Forshing Lui declares no relevant financial relationships with ineligible companies.\n\n**Disclosure:** Juan Carlos Sánchez-Manso declares no relevant financial relationships with ineligible companies.\n\n[Copyright](https:\/\/www.ncbi.nlm.nih.gov\/books\/about\/copyright\/) © 2025, StatPearls Publishing LLC.\n\nThis book is distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) ( [http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/](https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/) ), which permits others to distribute the work, provided that the article is not altered or used commercially. You are not required to obtain permission to distribute this article, provided that you credit the author and journal.\n\nBookshelf ID: NBK470171PMID: [29262094](https:\/\/pubmed.ncbi.nlm.nih.gov\/29262094 \"PubMed record of this page\")\n\n[Share](https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK470171\/)\n\n### Views\n- [PubReader](https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK470171\/?report=reader)\n- [Print View](https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK470171\/?report=printable)\n- [Cite this Page](https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK470171\/#_ncbi_dlg_citbx_NBK470171)\n  Aleksenko D, Lui F, Sánchez-Manso JC. Medication Overuse Headache. \\[Updated 2025 Jan 19\\]. In: StatPearls \\[Internet\\]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-.\n\n### In this Page\n- [Continuing Education Activity](https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK470171\/#article-24890.s1)\n- [Introduction](https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK470171\/#article-24890.s2)\n- [Etiology](https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK470171\/#article-24890.s3)\n- [Epidemiology](https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK470171\/#article-24890.s4)\n- [Pathophysiology](https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK470171\/#article-24890.s5)\n- [History and Physical](https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK470171\/#article-24890.s6)\n- [Evaluation](https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK470171\/#article-24890.s7)\n- [Treatment \/ Management](https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK470171\/#article-24890.s8)\n- [Differential Diagnosis](https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK470171\/#article-24890.s9)\n- [Prognosis](https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK470171\/#article-24890.s10)\n- [Complications](https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK470171\/#article-24890.s11)\n- [Deterrence and Patient Education](https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK470171\/#article-24890.s12)\n- [Pearls and Other Issues](https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK470171\/#article-24890.s13)\n- [Enhancing Healthcare Team Outcomes](https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK470171\/#article-24890.s14)\n- [Review Questions](https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK470171\/#article-24890.s15)\n- [References](https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK470171\/#article-24890.s16)\n\n### Related information\n- [PMC](https:\/\/www.ncbi.nlm.nih.gov\/books\/?Db=pmc&DbFrom=books&Cmd=Link&LinkName=books_pmc_refs&IdsFromResult=4479376)\n  PubMed Central citations\n- [PubMed](https:\/\/www.ncbi.nlm.nih.gov\/books\/?Db=pubmed&DbFrom=books&Cmd=Link&LinkName=books_pubmed_refs&IdsFromResult=4479376)\n  Links to PubMed\n\n### Similar articles in PubMed\n- [Review Comparing Two Ways to Manage Symptoms for Patients Who Have Chronic Migraine and Frequent Medication Use – The MOTS Trial](https:\/\/www.ncbi.nlm.nih.gov\/pubmed\/39432696)\\[ 2022\\]\n  Review Comparing Two Ways to Manage Symptoms for Patients Who Have Chronic Migraine and Frequent Medication Use – The MOTS Trial\n  \n  *Schwedt TJ, Dodick DW, Robert T, Hentz JG.* *2022 Feb*\n- [Transformed migraine and medication overuse in a tertiary headache centre--clinical characteristics and treatment outcomes.](https:\/\/www.ncbi.nlm.nih.gov\/pubmed\/15154858)\\[Cephalalgia. 2004\\]\n  Transformed migraine and medication overuse in a tertiary headache centre--clinical characteristics and treatment outcomes.\n  \n  *Bigal ME, Rapoport AM, Sheftell FD, Tepper SJ, Lipton RB.* *Cephalalgia. 2004 Jun; 24(6):483-90.*\n- [Medication-Overuse Headache.](https:\/\/www.ncbi.nlm.nih.gov\/pubmed\/30844177)\\[StatPearls. 2025\\]\n  Medication-Overuse Headache.\n  \n  *Fischer MA, Jan A.* *StatPearls. 2025 Jan*\n- [Prescription of Controlled Substances: Benefits and Risks.](https:\/\/www.ncbi.nlm.nih.gov\/pubmed\/30726003)\\[StatPearls. 2025\\]\n  Prescription of Controlled Substances: Benefits and Risks.\n  \n  *Preuss CV, Kalava A, King KC.* *StatPearls. 2025 Jan*\n- [Review Medication-overuse headache.](https:\/\/www.ncbi.nlm.nih.gov\/pubmed\/22868543)\\[Continuum (Minneap Minn). 2012\\]\n  Review Medication-overuse headache.\n  \n  *Tepper SJ.* *Continuum (Minneap Minn). 2012 Aug; 18(4):807-22.*\n\n[See reviews...](https:\/\/www.ncbi.nlm.nih.gov\/sites\/entrez?db=pubmed&cmd=link&linkname=pubmed_pubmed_reviews&uid=29262094)[See all...](https:\/\/www.ncbi.nlm.nih.gov\/sites\/entrez?db=pubmed&cmd=link&linkname=pubmed_pubmed&uid=29262094)\n\n### Recent Activity\n[Clear]()[Turn Off]()[Turn On]()\n\n- [Medication Overuse Headache - StatPearls](https:\/\/www.ncbi.nlm.nih.gov\/portal\/utils\/pageresolver.fcgi?recordid=699413d9dda9f256abba3ec2)\n  Medication Overuse Headache - StatPearls\n\nYour browsing activity is empty.\n\nActivity recording is turned off.\n\n[Turn recording back on]()\n\n[See more...](https:\/\/www.ncbi.nlm.nih.gov\/sites\/myncbi\/recentactivity)\n\nFollow NCBI\n\n[Connect with NLM](https:\/\/www.nlm.nih.gov\/socialmedia\/index.html)\n\nNational Library of Medicine  \n [8600 Rockville Pike  Bethesda, MD 20894](https:\/\/www.google.com\/maps\/place\/8600+Rockville+Pike,+Bethesda,+MD+20894\/@38.9959508,-77.101021,17z\/data=!3m1!4b1!4m5!3m4!1s0x89b7c95e25765ddb:0x19156f88b27635b8!8m2!3d38.9959508!4d-77.0988323)\n\n[Web Policies](https:\/\/www.nlm.nih.gov\/web_policies.html)  \n [FOIA](https:\/\/www.nih.gov\/institutes-nih\/nih-office-director\/office-communications-public-liaison\/freedom-information-act-office)  \n [HHS Vulnerability Disclosure](https:\/\/www.hhs.gov\/vulnerability-disclosure-policy\/index.html)\n\n[Help](https:\/\/support.nlm.nih.gov\/)  \n [Accessibility](https:\/\/www.nlm.nih.gov\/accessibility.html)  \n [Careers](https:\/\/www.nlm.nih.gov\/careers\/careers.html)\n\n- [NLM](https:\/\/www.nlm.nih.gov\/)\n- [NIH](https:\/\/www.nih.gov\/)\n- [HHS](https:\/\/www.hhs.gov\/)\n- [USA.gov](https:\/\/www.usa.gov\/)\n\n![statistics](https:\/\/www.ncbi.nlm.nih.gov\/stat?jsdisabled=true&ncbi_db=books&ncbi_pdid=book-part&ncbi_acc=NBK470171&ncbi_domain=statpearls&ncbi_report=record&ncbi_type=fulltext&ncbi_objectid=&ncbi_pcid=\/NBK470171\/&ncbi_pagename=Medication%20Overuse%20Headache%20-%20StatPearls%20-%20NCBI%20Bookshelf&ncbi_bookparttype=chapter&ncbi_app=bookshelf)","attrs_readable_markdown":"## Continuing Education Activity\nAccording to the International Classification of Headache Disorders, 3rd edition, a medication overuse headache is a secondary chronic headache disorder. This condition is defined as headaches occurring for 15 or more days per month for 3 or more months in patients taking acute headache treatments too frequently. Medication overuse headaches are believed to occur when medications intended to relieve headaches are consumed frequently. Causal agents are varied and can include agents such as nonsteroidal anti-inflammatory drugs, triptans, ergot derivatives, and opioids, although any analgesic can potentially trigger the medication overuse headache. This activity describes issues associated with the overuse of medications intended to relieve headaches and the evaluation and management of medication overuse headaches, highlighting the role of the interprofessional team in managing headaches.\n\n**Objectives:**\n\n- Identify the epidemiology of medication overuse headaches.\n- Assess the pathophysiology of medication overuse headaches.\n- Develop the various treatment options for managing medication overuse headaches.\n- Implement interprofessional team strategies for improving care coordination and communication to advance the prevention and management of medication overuse headaches and improve patient outcomes.\n\n[Access free multiple choice questions on this topic.](https:\/\/www.statpearls.com\/account\/trialuserreg\/?articleid=24890&utm_source=pubmed&utm_campaign=reviews&utm_content=24890)\n\n## Introduction\nAccording to the International Classification of Headache Disorders, 3rd edition (ICHD-3), a medication overuse headache is a secondary chronic headache disorder. This condition is defined as headaches occurring for 15 or more days per month for 3 or more months in patients who use acute headache treatments too frequently.[\\[1\\]](https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK470171\/#article-24890.r1) Medication overuse headaches are believed to occur when medications intended to relieve headaches are consumed too frequently, leading to a secondary type of headache. This condition was previously called a rebound headache and is commonly observed in individuals with migraine; the excessive use of analgesics can transform episodic headaches into a chronic condition. The exact frequency of using the pain-relieving drug before developing the medication overuse headache varies and depends on the particular type of medication used. Causal agents include both simple and combination analgesics, triptans, ergot derivatives, and opioids, but potentially any painkiller can be the trigger. Patients who use simple analgesics and nonsteroidal anti-inflammatory drugs (NSAIDs) for 15 or more days, or who take combination analgesics—including ergots; barbiturates, such as butalbital; triptans; and opioids—for 10 or more days per month are considered to have a medication overuse headache. Medication overuse headaches are common in patients at risk of overusing acute medications. Individuals previously diagnosed with a primary headache disorder, particularly migraines or tension-type headaches, are at risk of developing this condition. Medication overuse headaches typically resolve once the overused medication is reduced or discontinued.[\\[2\\]](https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK470171\/#article-24890.r2)[\\[3\\]](https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK470171\/#article-24890.r3)[\\[4\\]](https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK470171\/#article-24890.r4)[\\[5\\]](https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK470171\/#article-24890.r5)[\\[6\\]](https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK470171\/#article-24890.r6)\n\n## Etiology\nTo diagnose medication overuse headaches according to the latest ICHD-3 criteria, the following three conditions must be fulfilled:\n\n- A headache must occur 15 or more days per month in patients with a previously diagnosed headache disorder.\n- A patient must have misused the acute headache medication for 3 or more months.\n- A headache is not attributable to another ICHD-3 headache condition.\n\nMedication overuse headaches are believed to occur when patients frequently use acute headache medications at the following rates—15 or more days per month for simple analgesics, such as acetaminophen and NSAIDs, and 10 or more days per month for ergotamine, triptans, opioids, or combination analgesics, such as butalbital, acetaminophen, or caffeine.[\\[7\\]](https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK470171\/#article-24890.r7)[\\[8\\]](https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK470171\/#article-24890.r8)\n\nThe ICHD-3 states that when a combination of different headache medications is used, their combined frequency can lead to a medication overuse headache, even when the individual drugs are not overused separately.\n\nThe most common group of patients with medication overuse headaches are those with chronic migraine, who account for about two-thirds of patients with medication overuse headaches.\n\nPatients with headaches respond to acute medications differently. The use of an inappropriate headache abortive medication or less effective medication can increase the frequency of medication consumption and lead to medication overuse headaches. For example, due to the differences in efficacy between acetaminophen 1000 mg (NNT=12) and ibuprofen 400 mg (NNT=7.2), a patient using acetaminophen typically requires more frequent dosages to manage their headache compared to those using ibuprofen. The timing of acute headache treatment also affects the development of medication overuse headaches. Patients start medications for acute headaches, especially migraine medications, too late, which reduces their effectiveness. This underuse of both acute and preventive medications has been shown to contribute to the progression of migraine and subsequent medication overuse headaches.[\\[9\\]](https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK470171\/#article-24890.r9)\n\n## Epidemiology\nMedication overuse headaches are considered one of the more prevalent neurological disorders. The 2015 Global Burden of Disease study estimated its prevalence at 1% worldwide, affecting approximately 58.5 million people, which is lower compared to that of migraine and tension-type headaches. However, the same study ranked medication overuse headaches among the 20 most debilitating diseases.\n\nMedication overuse headaches occur relatively commonly in patients with chronic migraines, with about 32% of individuals in this group experiencing medication overuse headaches. Medication overuse headaches are believed to be more common in women, with a male-to-female ratio ranging from 2:1 to 5:1, and in those with low socioeconomic status.[\\[10\\]](https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK470171\/#article-24890.r10)\n\n## Pathophysiology\nThe exact mechanism of medication overuse headaches is unclear. However, it is hypothesized that medication overuse headaches result from the depletion of 5-HT due to the overuse of headache-abortive medications. This depletion leads to neuronal hyperexcitability in the cerebral cortex, which may result in cortical spreading depression, and the trigeminal system, which produces peripheral and central sensitization. The decrease in 5-HT levels leads to an increased release of calcitonin gene-related peptide from the trigeminal ganglia, which is involved in the subsequent sensitization of nociceptive trigeminal neurons.[\\[11\\]](https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK470171\/#article-24890.r11)\n\nOther studies have shown structural and functional brain changes in patients with medication overuse headaches. Morphometric magnetic resonance imaging has found increased gray matter volume in regions such as the midbrain, thalamus, and striatum. The midbrain gray matter volume changes resolved after removing the offending medication. The orbitofrontal cortical gray matter volume is lower in patients with medication overuse headaches, and a poor treatment response was observed.[\\[12\\]](https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK470171\/#article-24890.r12) PET scans of patients with medication overuse headaches reveal significant metabolic changes in various brain structures, most of which reverse upon the withdrawal of analgesic medication, except for persistent hypometabolism observed in the orbitofrontal area. This area is known to be involved in drug dependence and is hypothesized to be a risk factor for subsequent relapse in analgesic overuse and recurrent medication overuse headaches.[\\[13\\]](https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK470171\/#article-24890.r13)[\\[14\\]](https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK470171\/#article-24890.r14)[\\[13\\]](https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK470171\/#article-24890.r13)\n\n## History and Physical\nClinical presentation of medication overuse headaches varies among patients and may even change over time in the same individual. Patients may experience an increase in the frequency of a pre-existing headache or the development of a new type of headache. Since no specific tests exist for diagnosing this condition, the diagnosis relies on evaluating headache frequency, quantity, and the type and frequency of acute medication use.[\\[15\\]](https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK470171\/#article-24890.r15)\n\nAlthough pain location and quality are nonspecific in medication overuse headaches, certain general features are commonly observed in affected patients, including:\n\n- The headaches are typically episodic.\n- Frequent acute medication consumption depends on the type of abortive medication used. Generally, the threshold for developing medication overuse headaches is 15 or more days for acetaminophen and NSAIDs and 10 or more days for triptans, ergots, opioids, combination analgesics, and multiple drug classes.[\\[16\\]](https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK470171\/#article-24890.r16)\n- Neck pain is common and often mistaken for a cervicogenic headache, which in turn tends to be resistant to cervicalgia-appropriate treatments.\n- Typically occurs in the morning, presumed related to withdrawal occurring during sleep.\n- Poor sleep quality.\n- Autonomic symptoms, such as nasal congestion, rhinorrhea, and gastrointestinal disturbance, are more frequent with overused opioids.\n- Comorbid anxiety and depression.\n- All headache treatments are generally less effective in cases of medication overuse headaches; their efficacy improves after medication withdrawal.\n\n## Evaluation\nThere are currently no specific biomarkers or studies to differentiate or confirm medication overuse headaches. The diagnosis is entirely clinical and requires careful attention, as overlooking this condition can lead to its progression and worsening over time.\n\n## Treatment \/ Management\nEducation is the most crucial first step for patients with medication overuse headaches. Patients must understand and be aware of the headache issues related to their symptoms and misuse of headache remedies. Mindfulness has been shown to be an effective treatment strategy.[\\[17\\]](https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK470171\/#article-24890.r17)\n\nIn addition to education, the standard treatment of medication overuse headaches involves weaning the patient off the overused acute headache medication while simultaneously focusing on preventative treatment. Several studies show that complete discontinuation of overused acute medication yields the best outcomes compared to continuing the same acute medication with restricted frequency. Patients can be prescribed a new acute medication from a different class. Discontinuation can be achieved either abruptly (cold turkey) or gradually over several weeks. Preventative treatment can include prophylactic medication or nonpharmaceutical treatments, such as cognitive behavioral therapy, biofeedback, relaxation training, and lifestyle modification with trigger avoidance.[\\[18\\]](https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK470171\/#article-24890.r18)[\\[19\\]](https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK470171\/#article-24890.r19)[\\[20\\]](https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK470171\/#article-24890.r20)\n\nEducating patients and their families about the importance of limiting acute medication use is vital in preventing medication overuse headaches. Initial worsening of a headache within the first few days of weaning is relatively common. Withdrawal symptoms are believed to last up to 10 days, then eventually followed by improvement in medication overuse headaches.[\\[14\\]](https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK470171\/#article-24890.r14) Weaning patients off medication overuse headache-related medication can be done in an outpatient or an inpatient setting. Most cases can be managed in the outpatient setting, mainly through educating patients to cut down on their acute medication use. Addressing and treating comorbid psychiatric conditions, especially anxiety and depression, which are often associated with medication overuse headaches, are crucial. However, without enhancing the boosting effects, anxiolytic medication may contribute to the persistence of headaches.\n\nFollowing successful weaning, about 50% of patients relapse after 5 years; thus, it is essential to have the patient follow-up regularly. Once the patient's medication overuse headache has resolved, tapering them off the preventative medication may be considered. There are no specific guidelines, but some clinicians suggest tapering prophylactic medications after 1 year.[\\[21\\]](https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK470171\/#article-24890.r21)[\\[22\\]](https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK470171\/#article-24890.r22)\n\n## Differential Diagnosis\nA medication overuse headache occurs in patients with an episodic primary headache; thus, chronic versions of an episodic headache are one of the main differentials. The most common differential diagnosis of medication overuse headache is chronic migraine. Secondary headaches should be ruled out with the guidance of the patient's clinical presentation and the aid of all the necessary tests, especially when the features of the original episodic headache are different from their chronic counterparts.[\\[23\\]](https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK470171\/#article-24890.r23)[\\[24\\]](https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK470171\/#article-24890.r24)\n\n## Prognosis\nA tailored regime yields excellent long-term results; however, the estimated relapse rate is about 30% within 6 months and 50% following a 5-year period.[\\[25\\]](https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK470171\/#article-24890.r25)\n\n## Complications\nComplications associated with medication overuse headaches include additional symptoms linked to more severe and chronic forms of primary headache disorders. These symptoms include nausea, anxiety, irritability, asthenia, restlessness, difficulty concentrating, problems with memory, and depression.[\\[26\\]](https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK470171\/#article-24890.r26)\n\n## Deterrence and Patient Education\nEducation plays a crucial role in treating medication overuse headaches. Patients must understand the underlying causes of their headaches to adhere to changes in their medication regimen, which typically involves restricting their medication use. Depending on the drug used, patients may need to either discontinue the drug immediately or gradually taper the dose.\n\n## Pearls and Other Issues\nHealthcare professionals contend that frequent use of acute headache medications may indicate poorly controlled headaches and not necessarily the cause. This idea stems from evidence that not all patients improve when they stop taking headache-relieving medications. Instead of primarily blaming analgesic medication overuse as the reason for the increase in headache frequency, clinicians must be cautious in treating these patients and not overlook those in whom headaches are simply poorly controlled. Some studies suggested that other substances, such as the regular use of tranquilizers or other recreational substances abused in the general population, should be considered in conjunction with analgesics.\n\n## Enhancing Healthcare Team Outcomes\nThe diagnosis and management of medication overuse headaches are complex and best performed by an interprofessional team that includes clinicians, specialists, nursing staff, and pharmacists. Educating the patient and their family on the importance of limiting acute medication use is vital in preventing medication overuse headaches. The underlying psychiatric condition must be addressed, and a referral to a mental health professional can be helpful. All interprofessional team members are responsible for contributing from their areas of expertise, documenting any change in patient status, and communicating their observations with other team members as appropriate so therapeutic interventions can occur if necessary.\n\nFollowing successful weaning, about 50% of the patients relapse after 5 years, so regular follow-up is crucial. Once the patient's medication overuse headache has resolved, tapering them off the preventative medication may be considered. There are no specific guidelines, but some professionals suggest tapering prophylactic medication after 1 year.\n\n## References\n1\\.\n\nHeadache Classification Committee of the International Headache Society (IHS) The International Classification of Headache Disorders, 3rd edition. Cephalalgia. 2018 Jan;38(1):1-211. \\[[PubMed: 29368949](https:\/\/pubmed.ncbi.nlm.nih.gov\/29368949)\\]\n\n2\\.\n\nLimmer AL, Holland LC, Loftus BD. Zonisamide for Cluster Headache Prophylaxis: A Case Series. Headache. 2019 Jun;59(6):924-929. \\[[PubMed: 31038740](https:\/\/pubmed.ncbi.nlm.nih.gov\/31038740)\\]\n\n3\\.\n\nMose LS, Pedersen SS, Jensen RH, Gram B. Personality traits in migraine and medication-overuse headache: A comparative study. Acta Neurol Scand. 2019 Aug;140(2):116-122. \\[[PubMed: 31038726](https:\/\/pubmed.ncbi.nlm.nih.gov\/31038726)\\]\n\n4\\.\n\nYoung NP, Philpot LM, Vierkant RA, Rosedahl JK, Upadhyaya SG, Harris A, Ebbert JO. Episodic and Chronic Migraine in Primary Care. Headache. 2019 Jul;59(7):1042-1051. \\[[PMC free article: PMC6625910](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC6625910\/)\\] \\[[PubMed: 31032913](https:\/\/pubmed.ncbi.nlm.nih.gov\/31032913)\\]\n\n5\\.\n\nSandoe CH, Lay C. Secondary Headaches During Pregnancy: When to Worry. Curr Neurol Neurosci Rep. 2019 Apr 22;19(6):27. \\[[PubMed: 31011857](https:\/\/pubmed.ncbi.nlm.nih.gov\/31011857)\\]\n\n6\\.\n\nMicieli A, Kingston W. An Approach to Identifying Headache Patients That Require Neuroimaging. Front Public Health. 2019;7:52. \\[[PMC free article: PMC6428716](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC6428716\/)\\] \\[[PubMed: 30931292](https:\/\/pubmed.ncbi.nlm.nih.gov\/30931292)\\]\n\n7\\.\n\nGrazzi L, D'Amico D. Chronic migraine and medication overuse: which strategy for a complex scenario. Neurol Sci. 2019 May;40(Suppl 1):175-176. \\[[PubMed: 30906961](https:\/\/pubmed.ncbi.nlm.nih.gov\/30906961)\\]\n\n8\\.\n\nTurner DP, Lebowitz AD, Chtay I, Houle TT. Headache Triggers as Surprise. Headache. 2019 Apr;59(4):495-508. \\[[PMC free article: PMC6521840](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC6521840\/)\\] \\[[PubMed: 30919414](https:\/\/pubmed.ncbi.nlm.nih.gov\/30919414)\\]\n\n9\\.\n\nRattanawong W, Rapoport A, Srikiatkhachorn A. Medication \"underuse\" headache. Cephalalgia. 2024 Apr;44(4):3331024241245658. \\[[PubMed: 38613233](https:\/\/pubmed.ncbi.nlm.nih.gov\/38613233)\\]\n\n10\\.\n\nKulkarni GB, Mathew T, Mailankody P. Medication Overuse Headache. Neurol India. 2021 Mar-Apr;69(Supplement):S76-S82. \\[[PubMed: 34003151](https:\/\/pubmed.ncbi.nlm.nih.gov\/34003151)\\]\n\n11\\.\n\nPrakash S, Patel H, Shah CS. Medication-overuse headache overlapping with serotonin syndrome. BMJ Case Rep. 2024 Jan 04;17(1) \\[[PMC free article: PMC10773342](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC10773342\/)\\] \\[[PubMed: 38176752](https:\/\/pubmed.ncbi.nlm.nih.gov\/38176752)\\]\n\n12\\.\n\nRiederer F, Gantenbein AR, Marti M, Luechinger R, Kollias S, Sándor PS. Decrease of gray matter volume in the midbrain is associated with treatment response in medication-overuse headache: possible influence of orbitofrontal cortex. J Neurosci. 2013 Sep 25;33(39):15343-9. \\[[PMC free article: PMC6618461](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC6618461\/)\\] \\[[PubMed: 24068801](https:\/\/pubmed.ncbi.nlm.nih.gov\/24068801)\\]\n\n13\\.\n\nDripps IJ, Bertels Z, Moye LS, Tipton AF, Siegersma K, Baca SM, Kieffer BL, Pradhan AA. Forebrain delta opioid receptors regulate the response of delta agonist in models of migraine and opioid-induced hyperalgesia. Sci Rep. 2020 Oct 19;10(1):17629. \\[[PMC free article: PMC7573615](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC7573615\/)\\] \\[[PubMed: 33077757](https:\/\/pubmed.ncbi.nlm.nih.gov\/33077757)\\]\n\n14\\.\n\nSebastianelli G, Casillo F, Abagnale C, Di Renzo A, Ziccardi L, Parisi V, Di Lorenzo C, Serrao M, Coppola G. Neurophysiological Effects of Withdrawal from Acute Overused Medications in Chronic Migraine with Medication-Overuse Headache. J Clin Med. 2024 Dec 09;13(23) \\[[PMC free article: PMC11642649](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC11642649\/)\\] \\[[PubMed: 39685947](https:\/\/pubmed.ncbi.nlm.nih.gov\/39685947)\\]\n\n15\\.\n\nScher AI, Rizzoli PB, Loder EW. Medication overuse headache: An entrenched idea in need of scrutiny. Neurology. 2017 Sep 19;89(12):1296-1304. \\[[PubMed: 28821684](https:\/\/pubmed.ncbi.nlm.nih.gov\/28821684)\\]\n\n16\\.\n\nGosalia H, Moreno-Ajona D, Goadsby PJ. Medication-overuse headache: a narrative review. J Headache Pain. 2024 May 31;25(1):89. \\[[PMC free article: PMC11140994](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC11140994\/)\\] \\[[PubMed: 38816828](https:\/\/pubmed.ncbi.nlm.nih.gov\/38816828)\\]\n\n17\\.\n\nWells RE, O'Connell N, Pierce CR, Estave P, Penzien DB, Loder E, Zeidan F, Houle TT. Effectiveness of Mindfulness Meditation vs Headache Education for Adults With Migraine: A Randomized Clinical Trial. JAMA Intern Med. 2021 Mar 01;181(3):317-328. \\[[PMC free article: PMC7737157](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC7737157\/)\\] \\[[PubMed: 33315046](https:\/\/pubmed.ncbi.nlm.nih.gov\/33315046)\\]\n\n18\\.\n\nFerini-Strambi L, Galbiati A, Combi R. Sleep disorder-related headaches. Neurol Sci. 2019 May;40(Suppl 1):107-113. \\[[PubMed: 30906963](https:\/\/pubmed.ncbi.nlm.nih.gov\/30906963)\\]\n\n19\\.\n\nBarmherzig R, Kingston W. Occipital Neuralgia and Cervicogenic Headache: Diagnosis and Management. Curr Neurol Neurosci Rep. 2019 Mar 19;19(5):20. \\[[PubMed: 30888540](https:\/\/pubmed.ncbi.nlm.nih.gov\/30888540)\\]\n\n20\\.\n\nRussell MB. Epidemiology and management of medication-overuse headache in the general population. Neurol Sci. 2019 May;40(Suppl 1):23-26. \\[[PubMed: 30887240](https:\/\/pubmed.ncbi.nlm.nih.gov\/30887240)\\]\n\n21\\.\n\nArca KN, Halker Singh RB. The Hypertensive Headache: a Review. Curr Pain Headache Rep. 2019 Mar 14;23(5):30. \\[[PubMed: 30874912](https:\/\/pubmed.ncbi.nlm.nih.gov\/30874912)\\]\n\n22\\.\n\nBottiroli S, Galli F, Viana M, De Icco R, Bitetto V, Allena M, Pazzi S, Sances G, Tassorelli C. Negative Short-Term Outcome of Detoxification Therapy in Chronic Migraine With Medication Overuse Headache: Role for Early Life Traumatic Experiences and Recent Stressful Events. Front Neurol. 2019;10:173. \\[[PMC free article: PMC6416203](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC6416203\/)\\] \\[[PubMed: 30899242](https:\/\/pubmed.ncbi.nlm.nih.gov\/30899242)\\]\n\n23\\.\n\nSaengjaroentham C, Strother LC, Dripps I, Sultan Jabir MR, Pradhan A, Goadsby PJ, Holland PR. Differential medication overuse risk of novel anti-migraine therapeutics. Brain. 2020 Sep 01;143(9):2681-2688. \\[[PMC free article: PMC7523700](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC7523700\/)\\] \\[[PubMed: 32810212](https:\/\/pubmed.ncbi.nlm.nih.gov\/32810212)\\]\n\n24\\.\n\nLucas C, Diener HC. The dependence scale: an easy tool to detect chronic daily headache with medication overuse? J Neurol Neurosurg Psychiatry. 2009 Jul;80(7):704. \\[[PubMed: 19531683](https:\/\/pubmed.ncbi.nlm.nih.gov\/19531683)\\]\n\n25\\.\n\nMunksgaard SB, Madsen SK, Wienecke T. Treatment of medication overuse headache-A review. Acta Neurol Scand. 2019 May;139(5):405-414. \\[[PubMed: 30710346](https:\/\/pubmed.ncbi.nlm.nih.gov\/30710346)\\]\n\n26\\.\n\nDodick D, Freitag F. Evidence-based understanding of medication-overuse headache: clinical implications. Headache. 2006 Nov;46 Suppl 4:S202-11. \\[[PubMed: 17078852](https:\/\/pubmed.ncbi.nlm.nih.gov\/17078852)\\]\n\n**Disclosure:** Dmitri Aleksenko declares no relevant financial relationships with ineligible companies.\n\n**Disclosure:** Forshing Lui declares no relevant financial relationships with ineligible companies.\n\n**Disclosure:** Juan Carlos Sánchez-Manso declares no relevant financial relationships with ineligible companies.","meta_canonical":null}

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Meta Title	Medication Overuse Headache - StatPearls - NCBI Bookshelf
Meta Description	According to the International Classification of Headache Disorders, 3rd edition (ICHD-3), a medication overuse headache is a secondary chronic headache disorder. This condition is defined as headaches occurring for 15 or more days per month for 3 or more months in patients who use acute headache treatments too frequently.[1] Medication overuse headaches are believed to occur when medications intended to relieve headaches are consumed too frequently, leading to a secondary type of headache. This condition was previously called a rebound headache and is commonly observed in individuals with migraine; the excessive use of analgesics can transform episodic headaches into a chronic condition. The exact frequency of using the pain-relieving drug before developing the medication overuse headache varies and depends on the particular type of medication used. Causal agents include both simple and combination analgesics, triptans, ergot derivatives, and opioids, but potentially any painkiller can be the trigger. Patients who use simple analgesics and nonsteroidal anti-inflammatory drugs (NSAIDs) for 15 or more days, or who take combination analgesics—including ergots; barbiturates, such as butalbital; triptans; and opioids—for 10 or more days per month are considered to have a medication overuse headache. Medication overuse headaches are common in patients at risk of overusing acute medications. Individuals previously diagnosed with a primary headache disorder, particularly migraines or tension-type headaches, are at risk of developing this condition. Medication overuse headaches typically resolve once the overused medication is reduced or discontinued.[2][3][4][5][6]
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Boilerpipe Text	Continuing Education Activity According to the International Classification of Headache Disorders, 3rd edition, a medication overuse headache is a secondary chronic headache disorder. This condition is defined as headaches occurring for 15 or more days per month for 3 or more months in patients taking acute headache treatments too frequently. Medication overuse headaches are believed to occur when medications intended to relieve headaches are consumed frequently. Causal agents are varied and can include agents such as nonsteroidal anti-inflammatory drugs, triptans, ergot derivatives, and opioids, although any analgesic can potentially trigger the medication overuse headache. This activity describes issues associated with the overuse of medications intended to relieve headaches and the evaluation and management of medication overuse headaches, highlighting the role of the interprofessional team in managing headaches. Objectives: Identify the epidemiology of medication overuse headaches. Assess the pathophysiology of medication overuse headaches. Develop the various treatment options for managing medication overuse headaches. Implement interprofessional team strategies for improving care coordination and communication to advance the prevention and management of medication overuse headaches and improve patient outcomes. Access free multiple choice questions on this topic. Introduction According to the International Classification of Headache Disorders, 3rd edition (ICHD-3), a medication overuse headache is a secondary chronic headache disorder. This condition is defined as headaches occurring for 15 or more days per month for 3 or more months in patients who use acute headache treatments too frequently. [1] Medication overuse headaches are believed to occur when medications intended to relieve headaches are consumed too frequently, leading to a secondary type of headache. This condition was previously called a rebound headache and is commonly observed in individuals with migraine; the excessive use of analgesics can transform episodic headaches into a chronic condition. The exact frequency of using the pain-relieving drug before developing the medication overuse headache varies and depends on the particular type of medication used. Causal agents include both simple and combination analgesics, triptans, ergot derivatives, and opioids, but potentially any painkiller can be the trigger. Patients who use simple analgesics and nonsteroidal anti-inflammatory drugs (NSAIDs) for 15 or more days, or who take combination analgesics—including ergots; barbiturates, such as butalbital; triptans; and opioids—for 10 or more days per month are considered to have a medication overuse headache. Medication overuse headaches are common in patients at risk of overusing acute medications. Individuals previously diagnosed with a primary headache disorder, particularly migraines or tension-type headaches, are at risk of developing this condition. Medication overuse headaches typically resolve once the overused medication is reduced or discontinued. [2] [3] [4] [5] [6] Etiology To diagnose medication overuse headaches according to the latest ICHD-3 criteria, the following three conditions must be fulfilled: A headache must occur 15 or more days per month in patients with a previously diagnosed headache disorder. A patient must have misused the acute headache medication for 3 or more months. A headache is not attributable to another ICHD-3 headache condition. Medication overuse headaches are believed to occur when patients frequently use acute headache medications at the following rates—15 or more days per month for simple analgesics, such as acetaminophen and NSAIDs, and 10 or more days per month for ergotamine, triptans, opioids, or combination analgesics, such as butalbital, acetaminophen, or caffeine. [7] [8] The ICHD-3 states that when a combination of different headache medications is used, their combined frequency can lead to a medication overuse headache, even when the individual drugs are not overused separately. The most common group of patients with medication overuse headaches are those with chronic migraine, who account for about two-thirds of patients with medication overuse headaches. Patients with headaches respond to acute medications differently. The use of an inappropriate headache abortive medication or less effective medication can increase the frequency of medication consumption and lead to medication overuse headaches. For example, due to the differences in efficacy between acetaminophen 1000 mg (NNT=12) and ibuprofen 400 mg (NNT=7.2), a patient using acetaminophen typically requires more frequent dosages to manage their headache compared to those using ibuprofen. The timing of acute headache treatment also affects the development of medication overuse headaches. Patients start medications for acute headaches, especially migraine medications, too late, which reduces their effectiveness. This underuse of both acute and preventive medications has been shown to contribute to the progression of migraine and subsequent medication overuse headaches. [9] Epidemiology Medication overuse headaches are considered one of the more prevalent neurological disorders. The 2015 Global Burden of Disease study estimated its prevalence at 1% worldwide, affecting approximately 58.5 million people, which is lower compared to that of migraine and tension-type headaches. However, the same study ranked medication overuse headaches among the 20 most debilitating diseases. Medication overuse headaches occur relatively commonly in patients with chronic migraines, with about 32% of individuals in this group experiencing medication overuse headaches. Medication overuse headaches are believed to be more common in women, with a male-to-female ratio ranging from 2:1 to 5:1, and in those with low socioeconomic status. [10] Pathophysiology The exact mechanism of medication overuse headaches is unclear. However, it is hypothesized that medication overuse headaches result from the depletion of 5-HT due to the overuse of headache-abortive medications. This depletion leads to neuronal hyperexcitability in the cerebral cortex, which may result in cortical spreading depression, and the trigeminal system, which produces peripheral and central sensitization. The decrease in 5-HT levels leads to an increased release of calcitonin gene-related peptide from the trigeminal ganglia, which is involved in the subsequent sensitization of nociceptive trigeminal neurons. [11] Other studies have shown structural and functional brain changes in patients with medication overuse headaches. Morphometric magnetic resonance imaging has found increased gray matter volume in regions such as the midbrain, thalamus, and striatum. The midbrain gray matter volume changes resolved after removing the offending medication. The orbitofrontal cortical gray matter volume is lower in patients with medication overuse headaches, and a poor treatment response was observed. [12] PET scans of patients with medication overuse headaches reveal significant metabolic changes in various brain structures, most of which reverse upon the withdrawal of analgesic medication, except for persistent hypometabolism observed in the orbitofrontal area. This area is known to be involved in drug dependence and is hypothesized to be a risk factor for subsequent relapse in analgesic overuse and recurrent medication overuse headaches. [13] [14] [13] History and Physical Clinical presentation of medication overuse headaches varies among patients and may even change over time in the same individual. Patients may experience an increase in the frequency of a pre-existing headache or the development of a new type of headache. Since no specific tests exist for diagnosing this condition, the diagnosis relies on evaluating headache frequency, quantity, and the type and frequency of acute medication use. [15] Although pain location and quality are nonspecific in medication overuse headaches, certain general features are commonly observed in affected patients, including: The headaches are typically episodic. Frequent acute medication consumption depends on the type of abortive medication used. Generally, the threshold for developing medication overuse headaches is 15 or more days for acetaminophen and NSAIDs and 10 or more days for triptans, ergots, opioids, combination analgesics, and multiple drug classes. [16] Neck pain is common and often mistaken for a cervicogenic headache, which in turn tends to be resistant to cervicalgia-appropriate treatments. Typically occurs in the morning, presumed related to withdrawal occurring during sleep. Poor sleep quality. Autonomic symptoms, such as nasal congestion, rhinorrhea, and gastrointestinal disturbance, are more frequent with overused opioids. Comorbid anxiety and depression. All headache treatments are generally less effective in cases of medication overuse headaches; their efficacy improves after medication withdrawal. Evaluation There are currently no specific biomarkers or studies to differentiate or confirm medication overuse headaches. The diagnosis is entirely clinical and requires careful attention, as overlooking this condition can lead to its progression and worsening over time. Treatment / Management Education is the most crucial first step for patients with medication overuse headaches. Patients must understand and be aware of the headache issues related to their symptoms and misuse of headache remedies. Mindfulness has been shown to be an effective treatment strategy. [17] In addition to education, the standard treatment of medication overuse headaches involves weaning the patient off the overused acute headache medication while simultaneously focusing on preventative treatment. Several studies show that complete discontinuation of overused acute medication yields the best outcomes compared to continuing the same acute medication with restricted frequency. Patients can be prescribed a new acute medication from a different class. Discontinuation can be achieved either abruptly (cold turkey) or gradually over several weeks. Preventative treatment can include prophylactic medication or nonpharmaceutical treatments, such as cognitive behavioral therapy, biofeedback, relaxation training, and lifestyle modification with trigger avoidance. [18] [19] [20] Educating patients and their families about the importance of limiting acute medication use is vital in preventing medication overuse headaches. Initial worsening of a headache within the first few days of weaning is relatively common. Withdrawal symptoms are believed to last up to 10 days, then eventually followed by improvement in medication overuse headaches. [14] Weaning patients off medication overuse headache-related medication can be done in an outpatient or an inpatient setting. Most cases can be managed in the outpatient setting, mainly through educating patients to cut down on their acute medication use. Addressing and treating comorbid psychiatric conditions, especially anxiety and depression, which are often associated with medication overuse headaches, are crucial. However, without enhancing the boosting effects, anxiolytic medication may contribute to the persistence of headaches. Following successful weaning, about 50% of patients relapse after 5 years; thus, it is essential to have the patient follow-up regularly. Once the patient's medication overuse headache has resolved, tapering them off the preventative medication may be considered. There are no specific guidelines, but some clinicians suggest tapering prophylactic medications after 1 year. [21] [22] Differential Diagnosis A medication overuse headache occurs in patients with an episodic primary headache; thus, chronic versions of an episodic headache are one of the main differentials. The most common differential diagnosis of medication overuse headache is chronic migraine. Secondary headaches should be ruled out with the guidance of the patient's clinical presentation and the aid of all the necessary tests, especially when the features of the original episodic headache are different from their chronic counterparts. [23] [24] Prognosis A tailored regime yields excellent long-term results; however, the estimated relapse rate is about 30% within 6 months and 50% following a 5-year period. [25] Complications Complications associated with medication overuse headaches include additional symptoms linked to more severe and chronic forms of primary headache disorders. These symptoms include nausea, anxiety, irritability, asthenia, restlessness, difficulty concentrating, problems with memory, and depression. [26] Deterrence and Patient Education Education plays a crucial role in treating medication overuse headaches. Patients must understand the underlying causes of their headaches to adhere to changes in their medication regimen, which typically involves restricting their medication use. Depending on the drug used, patients may need to either discontinue the drug immediately or gradually taper the dose. Pearls and Other Issues Healthcare professionals contend that frequent use of acute headache medications may indicate poorly controlled headaches and not necessarily the cause. This idea stems from evidence that not all patients improve when they stop taking headache-relieving medications. Instead of primarily blaming analgesic medication overuse as the reason for the increase in headache frequency, clinicians must be cautious in treating these patients and not overlook those in whom headaches are simply poorly controlled. Some studies suggested that other substances, such as the regular use of tranquilizers or other recreational substances abused in the general population, should be considered in conjunction with analgesics. Enhancing Healthcare Team Outcomes The diagnosis and management of medication overuse headaches are complex and best performed by an interprofessional team that includes clinicians, specialists, nursing staff, and pharmacists. Educating the patient and their family on the importance of limiting acute medication use is vital in preventing medication overuse headaches. The underlying psychiatric condition must be addressed, and a referral to a mental health professional can be helpful. All interprofessional team members are responsible for contributing from their areas of expertise, documenting any change in patient status, and communicating their observations with other team members as appropriate so therapeutic interventions can occur if necessary. Following successful weaning, about 50% of the patients relapse after 5 years, so regular follow-up is crucial. Once the patient's medication overuse headache has resolved, tapering them off the preventative medication may be considered. There are no specific guidelines, but some professionals suggest tapering prophylactic medication after 1 year. References 1. Headache Classification Committee of the International Headache Society (IHS) The International Classification of Headache Disorders, 3rd edition. Cephalalgia. 2018 Jan; 38 (1):1-211. [ PubMed : 29368949 ] 2. Limmer AL, Holland LC, Loftus BD. Zonisamide for Cluster Headache Prophylaxis: A Case Series. Headache. 2019 Jun; 59 (6):924-929. [ PubMed : 31038740 ] 3. Mose LS, Pedersen SS, Jensen RH, Gram B. Personality traits in migraine and medication-overuse headache: A comparative study. Acta Neurol Scand. 2019 Aug; 140 (2):116-122. [ PubMed : 31038726 ] 4. Young NP, Philpot LM, Vierkant RA, Rosedahl JK, Upadhyaya SG, Harris A, Ebbert JO. Episodic and Chronic Migraine in Primary Care. Headache. 2019 Jul; 59 (7):1042-1051. [ PMC free article : PMC6625910 ] [ PubMed : 31032913 ] 5. Sandoe CH, Lay C. Secondary Headaches During Pregnancy: When to Worry. Curr Neurol Neurosci Rep. 2019 Apr 22; 19 (6):27. [ PubMed : 31011857 ] 6. Micieli A, Kingston W. An Approach to Identifying Headache Patients That Require Neuroimaging. Front Public Health. 2019; 7 :52. [ PMC free article : PMC6428716 ] [ PubMed : 30931292 ] 7. Grazzi L, D'Amico D. Chronic migraine and medication overuse: which strategy for a complex scenario. Neurol Sci. 2019 May; 40 (Suppl 1):175-176. [ PubMed : 30906961 ] 8. Turner DP, Lebowitz AD, Chtay I, Houle TT. Headache Triggers as Surprise. Headache. 2019 Apr; 59 (4):495-508. [ PMC free article : PMC6521840 ] [ PubMed : 30919414 ] 9. Rattanawong W, Rapoport A, Srikiatkhachorn A. Medication "underuse" headache. Cephalalgia. 2024 Apr; 44 (4):3331024241245658. [ PubMed : 38613233 ] 10. Kulkarni GB, Mathew T, Mailankody P. Medication Overuse Headache. Neurol India. 2021 Mar-Apr; 69 (Supplement):S76-S82. [ PubMed : 34003151 ] 11. Prakash S, Patel H, Shah CS. Medication-overuse headache overlapping with serotonin syndrome. BMJ Case Rep. 2024 Jan 04; 17 (1) [ PMC free article : PMC10773342 ] [ PubMed : 38176752 ] 12. Riederer F, Gantenbein AR, Marti M, Luechinger R, Kollias S, Sándor PS. Decrease of gray matter volume in the midbrain is associated with treatment response in medication-overuse headache: possible influence of orbitofrontal cortex. J Neurosci. 2013 Sep 25; 33 (39):15343-9. [ PMC free article : PMC6618461 ] [ PubMed : 24068801 ] 13. Dripps IJ, Bertels Z, Moye LS, Tipton AF, Siegersma K, Baca SM, Kieffer BL, Pradhan AA. Forebrain delta opioid receptors regulate the response of delta agonist in models of migraine and opioid-induced hyperalgesia. Sci Rep. 2020 Oct 19; 10 (1):17629. [ PMC free article : PMC7573615 ] [ PubMed : 33077757 ] 14. Sebastianelli G, Casillo F, Abagnale C, Di Renzo A, Ziccardi L, Parisi V, Di Lorenzo C, Serrao M, Coppola G. Neurophysiological Effects of Withdrawal from Acute Overused Medications in Chronic Migraine with Medication-Overuse Headache. J Clin Med. 2024 Dec 09; 13 (23) [ PMC free article : PMC11642649 ] [ PubMed : 39685947 ] 15. Scher AI, Rizzoli PB, Loder EW. Medication overuse headache: An entrenched idea in need of scrutiny. Neurology. 2017 Sep 19; 89 (12):1296-1304. [ PubMed : 28821684 ] 16. Gosalia H, Moreno-Ajona D, Goadsby PJ. Medication-overuse headache: a narrative review. J Headache Pain. 2024 May 31; 25 (1):89. [ PMC free article : PMC11140994 ] [ PubMed : 38816828 ] 17. Wells RE, O'Connell N, Pierce CR, Estave P, Penzien DB, Loder E, Zeidan F, Houle TT. Effectiveness of Mindfulness Meditation vs Headache Education for Adults With Migraine: A Randomized Clinical Trial. JAMA Intern Med. 2021 Mar 01; 181 (3):317-328. [ PMC free article : PMC7737157 ] [ PubMed : 33315046 ] 18. Ferini-Strambi L, Galbiati A, Combi R. Sleep disorder-related headaches. Neurol Sci. 2019 May; 40 (Suppl 1):107-113. [ PubMed : 30906963 ] 19. Barmherzig R, Kingston W. Occipital Neuralgia and Cervicogenic Headache: Diagnosis and Management. Curr Neurol Neurosci Rep. 2019 Mar 19; 19 (5):20. [ PubMed : 30888540 ] 20. Russell MB. Epidemiology and management of medication-overuse headache in the general population. Neurol Sci. 2019 May; 40 (Suppl 1):23-26. [ PubMed : 30887240 ] 21. Arca KN, Halker Singh RB. The Hypertensive Headache: a Review. Curr Pain Headache Rep. 2019 Mar 14; 23 (5):30. [ PubMed : 30874912 ] 22. Bottiroli S, Galli F, Viana M, De Icco R, Bitetto V, Allena M, Pazzi S, Sances G, Tassorelli C. Negative Short-Term Outcome of Detoxification Therapy in Chronic Migraine With Medication Overuse Headache: Role for Early Life Traumatic Experiences and Recent Stressful Events. Front Neurol. 2019; 10 :173. [ PMC free article : PMC6416203 ] [ PubMed : 30899242 ] 23. Saengjaroentham C, Strother LC, Dripps I, Sultan Jabir MR, Pradhan A, Goadsby PJ, Holland PR. Differential medication overuse risk of novel anti-migraine therapeutics. Brain. 2020 Sep 01; 143 (9):2681-2688. [ PMC free article : PMC7523700 ] [ PubMed : 32810212 ] 24. Lucas C, Diener HC. The dependence scale: an easy tool to detect chronic daily headache with medication overuse? J Neurol Neurosurg Psychiatry. 2009 Jul; 80 (7):704. [ PubMed : 19531683 ] 25. Munksgaard SB, Madsen SK, Wienecke T. Treatment of medication overuse headache-A review. Acta Neurol Scand. 2019 May; 139 (5):405-414. [ PubMed : 30710346 ] 26. Dodick D, Freitag F. Evidence-based understanding of medication-overuse headache: clinical implications. Headache. 2006 Nov; 46 Suppl 4 :S202-11. [ PubMed : 17078852 ] Disclosure: Dmitri Aleksenko declares no relevant financial relationships with ineligible companies. Disclosure: Forshing Lui declares no relevant financial relationships with ineligible companies. Disclosure: Juan Carlos Sánchez-Manso declares no relevant financial relationships with ineligible companies.
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A service of the National Library of Medicine, National Institutes of Health. StatPearls \[Internet\]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. [![Cover of StatPearls](https://www.ncbi.nlm.nih.gov/corehtml/pmc/pmcgifs/bookshelf/thumbs/th-statpearls-lrg.png)](https://www.ncbi.nlm.nih.gov/books/n/statpearls/ "Table of Contents Page") ## StatPearls \[Internet\]. [Show details](https://www.ncbi.nlm.nih.gov/books/NBK470171/#__NBK470171_dtls__) Treasure Island (FL): [StatPearls Publishing](https://www.statpearls.com/); 2025 Jan-. # Medication Overuse Headache Dmitri Aleksenko; Forshing Lui; Juan Carlos Sánchez-Manso. [Author Information and Affiliations](https://www.ncbi.nlm.nih.gov/books/NBK470171/#__NBK470171_ai__) #### Authors Dmitri Aleksenko1; Forshing Lui2; Juan Carlos Sánchez-Manso3. #### Affiliations 1 Louisiana State University HSC 2 CA Northstate Uni, College of Med 3 Hospital Nuestra Señora del Rosario Last Update: January 19, 2025. ## Continuing Education Activity According to the International Classification of Headache Disorders, 3rd edition, a medication overuse headache is a secondary chronic headache disorder. This condition is defined as headaches occurring for 15 or more days per month for 3 or more months in patients taking acute headache treatments too frequently. Medication overuse headaches are believed to occur when medications intended to relieve headaches are consumed frequently. Causal agents are varied and can include agents such as nonsteroidal anti-inflammatory drugs, triptans, ergot derivatives, and opioids, although any analgesic can potentially trigger the medication overuse headache. This activity describes issues associated with the overuse of medications intended to relieve headaches and the evaluation and management of medication overuse headaches, highlighting the role of the interprofessional team in managing headaches. Objectives: - Identify the epidemiology of medication overuse headaches. - Assess the pathophysiology of medication overuse headaches. - Develop the various treatment options for managing medication overuse headaches. - Implement interprofessional team strategies for improving care coordination and communication to advance the prevention and management of medication overuse headaches and improve patient outcomes. [Access free multiple choice questions on this topic.](https://www.statpearls.com/account/trialuserreg/?articleid=24890&utm_source=pubmed&utm_campaign=reviews&utm_content=24890) ## Introduction According to the International Classification of Headache Disorders, 3rd edition (ICHD-3), a medication overuse headache is a secondary chronic headache disorder. This condition is defined as headaches occurring for 15 or more days per month for 3 or more months in patients who use acute headache treatments too frequently.[\[1\]](https://www.ncbi.nlm.nih.gov/books/NBK470171/#article-24890.r1) Medication overuse headaches are believed to occur when medications intended to relieve headaches are consumed too frequently, leading to a secondary type of headache. This condition was previously called a rebound headache and is commonly observed in individuals with migraine; the excessive use of analgesics can transform episodic headaches into a chronic condition. The exact frequency of using the pain-relieving drug before developing the medication overuse headache varies and depends on the particular type of medication used. Causal agents include both simple and combination analgesics, triptans, ergot derivatives, and opioids, but potentially any painkiller can be the trigger. Patients who use simple analgesics and nonsteroidal anti-inflammatory drugs (NSAIDs) for 15 or more days, or who take combination analgesics—including ergots; barbiturates, such as butalbital; triptans; and opioids—for 10 or more days per month are considered to have a medication overuse headache. Medication overuse headaches are common in patients at risk of overusing acute medications. Individuals previously diagnosed with a primary headache disorder, particularly migraines or tension-type headaches, are at risk of developing this condition. Medication overuse headaches typically resolve once the overused medication is reduced or discontinued.[\[2\]](https://www.ncbi.nlm.nih.gov/books/NBK470171/#article-24890.r2)[\[3\]](https://www.ncbi.nlm.nih.gov/books/NBK470171/#article-24890.r3)[\[4\]](https://www.ncbi.nlm.nih.gov/books/NBK470171/#article-24890.r4)[\[5\]](https://www.ncbi.nlm.nih.gov/books/NBK470171/#article-24890.r5)[\[6\]](https://www.ncbi.nlm.nih.gov/books/NBK470171/#article-24890.r6) ## Etiology To diagnose medication overuse headaches according to the latest ICHD-3 criteria, the following three conditions must be fulfilled: - A headache must occur 15 or more days per month in patients with a previously diagnosed headache disorder. - A patient must have misused the acute headache medication for 3 or more months. - A headache is not attributable to another ICHD-3 headache condition. Medication overuse headaches are believed to occur when patients frequently use acute headache medications at the following rates—15 or more days per month for simple analgesics, such as acetaminophen and NSAIDs, and 10 or more days per month for ergotamine, triptans, opioids, or combination analgesics, such as butalbital, acetaminophen, or caffeine.[\[7\]](https://www.ncbi.nlm.nih.gov/books/NBK470171/#article-24890.r7)[\[8\]](https://www.ncbi.nlm.nih.gov/books/NBK470171/#article-24890.r8) The ICHD-3 states that when a combination of different headache medications is used, their combined frequency can lead to a medication overuse headache, even when the individual drugs are not overused separately. The most common group of patients with medication overuse headaches are those with chronic migraine, who account for about two-thirds of patients with medication overuse headaches. Patients with headaches respond to acute medications differently. The use of an inappropriate headache abortive medication or less effective medication can increase the frequency of medication consumption and lead to medication overuse headaches. For example, due to the differences in efficacy between acetaminophen 1000 mg (NNT=12) and ibuprofen 400 mg (NNT=7.2), a patient using acetaminophen typically requires more frequent dosages to manage their headache compared to those using ibuprofen. The timing of acute headache treatment also affects the development of medication overuse headaches. Patients start medications for acute headaches, especially migraine medications, too late, which reduces their effectiveness. This underuse of both acute and preventive medications has been shown to contribute to the progression of migraine and subsequent medication overuse headaches.[\[9\]](https://www.ncbi.nlm.nih.gov/books/NBK470171/#article-24890.r9) ## Epidemiology Medication overuse headaches are considered one of the more prevalent neurological disorders. The 2015 Global Burden of Disease study estimated its prevalence at 1% worldwide, affecting approximately 58.5 million people, which is lower compared to that of migraine and tension-type headaches. However, the same study ranked medication overuse headaches among the 20 most debilitating diseases. Medication overuse headaches occur relatively commonly in patients with chronic migraines, with about 32% of individuals in this group experiencing medication overuse headaches. Medication overuse headaches are believed to be more common in women, with a male-to-female ratio ranging from 2:1 to 5:1, and in those with low socioeconomic status.[\[10\]](https://www.ncbi.nlm.nih.gov/books/NBK470171/#article-24890.r10) ## Pathophysiology The exact mechanism of medication overuse headaches is unclear. However, it is hypothesized that medication overuse headaches result from the depletion of 5-HT due to the overuse of headache-abortive medications. This depletion leads to neuronal hyperexcitability in the cerebral cortex, which may result in cortical spreading depression, and the trigeminal system, which produces peripheral and central sensitization. The decrease in 5-HT levels leads to an increased release of calcitonin gene-related peptide from the trigeminal ganglia, which is involved in the subsequent sensitization of nociceptive trigeminal neurons.[\[11\]](https://www.ncbi.nlm.nih.gov/books/NBK470171/#article-24890.r11) Other studies have shown structural and functional brain changes in patients with medication overuse headaches. Morphometric magnetic resonance imaging has found increased gray matter volume in regions such as the midbrain, thalamus, and striatum. The midbrain gray matter volume changes resolved after removing the offending medication. The orbitofrontal cortical gray matter volume is lower in patients with medication overuse headaches, and a poor treatment response was observed.[\[12\]](https://www.ncbi.nlm.nih.gov/books/NBK470171/#article-24890.r12) PET scans of patients with medication overuse headaches reveal significant metabolic changes in various brain structures, most of which reverse upon the withdrawal of analgesic medication, except for persistent hypometabolism observed in the orbitofrontal area. This area is known to be involved in drug dependence and is hypothesized to be a risk factor for subsequent relapse in analgesic overuse and recurrent medication overuse headaches.[\[13\]](https://www.ncbi.nlm.nih.gov/books/NBK470171/#article-24890.r13)[\[14\]](https://www.ncbi.nlm.nih.gov/books/NBK470171/#article-24890.r14)[\[13\]](https://www.ncbi.nlm.nih.gov/books/NBK470171/#article-24890.r13) ## History and Physical Clinical presentation of medication overuse headaches varies among patients and may even change over time in the same individual. Patients may experience an increase in the frequency of a pre-existing headache or the development of a new type of headache. Since no specific tests exist for diagnosing this condition, the diagnosis relies on evaluating headache frequency, quantity, and the type and frequency of acute medication use.[\[15\]](https://www.ncbi.nlm.nih.gov/books/NBK470171/#article-24890.r15) Although pain location and quality are nonspecific in medication overuse headaches, certain general features are commonly observed in affected patients, including: - The headaches are typically episodic. - Frequent acute medication consumption depends on the type of abortive medication used. Generally, the threshold for developing medication overuse headaches is 15 or more days for acetaminophen and NSAIDs and 10 or more days for triptans, ergots, opioids, combination analgesics, and multiple drug classes.[\[16\]](https://www.ncbi.nlm.nih.gov/books/NBK470171/#article-24890.r16) - Neck pain is common and often mistaken for a cervicogenic headache, which in turn tends to be resistant to cervicalgia-appropriate treatments. - Typically occurs in the morning, presumed related to withdrawal occurring during sleep. - Poor sleep quality. - Autonomic symptoms, such as nasal congestion, rhinorrhea, and gastrointestinal disturbance, are more frequent with overused opioids. - Comorbid anxiety and depression. - All headache treatments are generally less effective in cases of medication overuse headaches; their efficacy improves after medication withdrawal. ## Evaluation There are currently no specific biomarkers or studies to differentiate or confirm medication overuse headaches. The diagnosis is entirely clinical and requires careful attention, as overlooking this condition can lead to its progression and worsening over time. ## Treatment / Management Education is the most crucial first step for patients with medication overuse headaches. Patients must understand and be aware of the headache issues related to their symptoms and misuse of headache remedies. Mindfulness has been shown to be an effective treatment strategy.[\[17\]](https://www.ncbi.nlm.nih.gov/books/NBK470171/#article-24890.r17) In addition to education, the standard treatment of medication overuse headaches involves weaning the patient off the overused acute headache medication while simultaneously focusing on preventative treatment. Several studies show that complete discontinuation of overused acute medication yields the best outcomes compared to continuing the same acute medication with restricted frequency. Patients can be prescribed a new acute medication from a different class. Discontinuation can be achieved either abruptly (cold turkey) or gradually over several weeks. Preventative treatment can include prophylactic medication or nonpharmaceutical treatments, such as cognitive behavioral therapy, biofeedback, relaxation training, and lifestyle modification with trigger avoidance.[\[18\]](https://www.ncbi.nlm.nih.gov/books/NBK470171/#article-24890.r18)[\[19\]](https://www.ncbi.nlm.nih.gov/books/NBK470171/#article-24890.r19)[\[20\]](https://www.ncbi.nlm.nih.gov/books/NBK470171/#article-24890.r20) Educating patients and their families about the importance of limiting acute medication use is vital in preventing medication overuse headaches. Initial worsening of a headache within the first few days of weaning is relatively common. Withdrawal symptoms are believed to last up to 10 days, then eventually followed by improvement in medication overuse headaches.[\[14\]](https://www.ncbi.nlm.nih.gov/books/NBK470171/#article-24890.r14) Weaning patients off medication overuse headache-related medication can be done in an outpatient or an inpatient setting. Most cases can be managed in the outpatient setting, mainly through educating patients to cut down on their acute medication use. Addressing and treating comorbid psychiatric conditions, especially anxiety and depression, which are often associated with medication overuse headaches, are crucial. However, without enhancing the boosting effects, anxiolytic medication may contribute to the persistence of headaches. Following successful weaning, about 50% of patients relapse after 5 years; thus, it is essential to have the patient follow-up regularly. Once the patient's medication overuse headache has resolved, tapering them off the preventative medication may be considered. There are no specific guidelines, but some clinicians suggest tapering prophylactic medications after 1 year.[\[21\]](https://www.ncbi.nlm.nih.gov/books/NBK470171/#article-24890.r21)[\[22\]](https://www.ncbi.nlm.nih.gov/books/NBK470171/#article-24890.r22) ## Differential Diagnosis A medication overuse headache occurs in patients with an episodic primary headache; thus, chronic versions of an episodic headache are one of the main differentials. The most common differential diagnosis of medication overuse headache is chronic migraine. Secondary headaches should be ruled out with the guidance of the patient's clinical presentation and the aid of all the necessary tests, especially when the features of the original episodic headache are different from their chronic counterparts.[\[23\]](https://www.ncbi.nlm.nih.gov/books/NBK470171/#article-24890.r23)[\[24\]](https://www.ncbi.nlm.nih.gov/books/NBK470171/#article-24890.r24) ## Prognosis A tailored regime yields excellent long-term results; however, the estimated relapse rate is about 30% within 6 months and 50% following a 5-year period.[\[25\]](https://www.ncbi.nlm.nih.gov/books/NBK470171/#article-24890.r25) ## Complications Complications associated with medication overuse headaches include additional symptoms linked to more severe and chronic forms of primary headache disorders. These symptoms include nausea, anxiety, irritability, asthenia, restlessness, difficulty concentrating, problems with memory, and depression.[\[26\]](https://www.ncbi.nlm.nih.gov/books/NBK470171/#article-24890.r26) ## Deterrence and Patient Education Education plays a crucial role in treating medication overuse headaches. Patients must understand the underlying causes of their headaches to adhere to changes in their medication regimen, which typically involves restricting their medication use. Depending on the drug used, patients may need to either discontinue the drug immediately or gradually taper the dose. ## Pearls and Other Issues Healthcare professionals contend that frequent use of acute headache medications may indicate poorly controlled headaches and not necessarily the cause. This idea stems from evidence that not all patients improve when they stop taking headache-relieving medications. Instead of primarily blaming analgesic medication overuse as the reason for the increase in headache frequency, clinicians must be cautious in treating these patients and not overlook those in whom headaches are simply poorly controlled. Some studies suggested that other substances, such as the regular use of tranquilizers or other recreational substances abused in the general population, should be considered in conjunction with analgesics. ## Enhancing Healthcare Team Outcomes The diagnosis and management of medication overuse headaches are complex and best performed by an interprofessional team that includes clinicians, specialists, nursing staff, and pharmacists. Educating the patient and their family on the importance of limiting acute medication use is vital in preventing medication overuse headaches. The underlying psychiatric condition must be addressed, and a referral to a mental health professional can be helpful. All interprofessional team members are responsible for contributing from their areas of expertise, documenting any change in patient status, and communicating their observations with other team members as appropriate so therapeutic interventions can occur if necessary. Following successful weaning, about 50% of the patients relapse after 5 years, so regular follow-up is crucial. Once the patient's medication overuse headache has resolved, tapering them off the preventative medication may be considered. There are no specific guidelines, but some professionals suggest tapering prophylactic medication after 1 year. ## Review Questions - [Access free multiple choice questions on this topic.](https://www.statpearls.com/account/trialuserreg/?articleid=24890&utm_source=pubmed&utm_campaign=reviews&utm_content=24890) - [Click here for a simplified version.](https://mdsearchlight.com/migraine-headaches/headache-from-medication-overuse/?utm_source=pubmedlink&utm_campaign=MDS&utm_content=24890) - [Comment on this article.](https://www.statpearls.com/articlelibrary/commentarticle/24890/?utm_source=pubmed&utm_campaign=comments&utm_content=24890) ## References 1\. Headache Classification Committee of the International Headache Society (IHS) The International Classification of Headache Disorders, 3rd edition. Cephalalgia. 2018 Jan;38(1):1-211. \[[PubMed: 29368949](https://pubmed.ncbi.nlm.nih.gov/29368949)\] 2\. Limmer AL, Holland LC, Loftus BD. 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Saengjaroentham C, Strother LC, Dripps I, Sultan Jabir MR, Pradhan A, Goadsby PJ, Holland PR. Differential medication overuse risk of novel anti-migraine therapeutics. Brain. 2020 Sep 01;143(9):2681-2688. \[[PMC free article: PMC7523700](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7523700/)\] \[[PubMed: 32810212](https://pubmed.ncbi.nlm.nih.gov/32810212)\] 24\. Lucas C, Diener HC. The dependence scale: an easy tool to detect chronic daily headache with medication overuse? J Neurol Neurosurg Psychiatry. 2009 Jul;80(7):704. \[[PubMed: 19531683](https://pubmed.ncbi.nlm.nih.gov/19531683)\] 25\. Munksgaard SB, Madsen SK, Wienecke T. Treatment of medication overuse headache-A review. Acta Neurol Scand. 2019 May;139(5):405-414. \[[PubMed: 30710346](https://pubmed.ncbi.nlm.nih.gov/30710346)\] 26\. Dodick D, Freitag F. Evidence-based understanding of medication-overuse headache: clinical implications. Headache. 2006 Nov;46 Suppl 4:S202-11. \[[PubMed: 17078852](https://pubmed.ncbi.nlm.nih.gov/17078852)\] Disclosure: Dmitri Aleksenko declares no relevant financial relationships with ineligible companies. Disclosure: Forshing Lui declares no relevant financial relationships with ineligible companies. Disclosure: Juan Carlos Sánchez-Manso declares no relevant financial relationships with ineligible companies. [Copyright](https://www.ncbi.nlm.nih.gov/books/about/copyright/) © 2025, StatPearls Publishing LLC. This book is distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) ( [http://creativecommons.org/licenses/by-nc-nd/4.0/](https://creativecommons.org/licenses/by-nc-nd/4.0/) ), which permits others to distribute the work, provided that the article is not altered or used commercially. You are not required to obtain permission to distribute this article, provided that you credit the author and journal. 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Treasure Island (FL): StatPearls Publishing; 2025 Jan-. ### In this Page - [Continuing Education Activity](https://www.ncbi.nlm.nih.gov/books/NBK470171/#article-24890.s1) - [Introduction](https://www.ncbi.nlm.nih.gov/books/NBK470171/#article-24890.s2) - [Etiology](https://www.ncbi.nlm.nih.gov/books/NBK470171/#article-24890.s3) - [Epidemiology](https://www.ncbi.nlm.nih.gov/books/NBK470171/#article-24890.s4) - [Pathophysiology](https://www.ncbi.nlm.nih.gov/books/NBK470171/#article-24890.s5) - [History and Physical](https://www.ncbi.nlm.nih.gov/books/NBK470171/#article-24890.s6) - [Evaluation](https://www.ncbi.nlm.nih.gov/books/NBK470171/#article-24890.s7) - [Treatment / Management](https://www.ncbi.nlm.nih.gov/books/NBK470171/#article-24890.s8) - [Differential Diagnosis](https://www.ncbi.nlm.nih.gov/books/NBK470171/#article-24890.s9) - [Prognosis](https://www.ncbi.nlm.nih.gov/books/NBK470171/#article-24890.s10) - [Complications](https://www.ncbi.nlm.nih.gov/books/NBK470171/#article-24890.s11) - [Deterrence and Patient Education](https://www.ncbi.nlm.nih.gov/books/NBK470171/#article-24890.s12) - [Pearls and Other Issues](https://www.ncbi.nlm.nih.gov/books/NBK470171/#article-24890.s13) - [Enhancing Healthcare Team Outcomes](https://www.ncbi.nlm.nih.gov/books/NBK470171/#article-24890.s14) - [Review Questions](https://www.ncbi.nlm.nih.gov/books/NBK470171/#article-24890.s15) - [References](https://www.ncbi.nlm.nih.gov/books/NBK470171/#article-24890.s16) ### Related information - [PMC](https://www.ncbi.nlm.nih.gov/books/?Db=pmc&DbFrom=books&Cmd=Link&LinkName=books_pmc_refs&IdsFromResult=4479376) PubMed Central citations - [PubMed](https://www.ncbi.nlm.nih.gov/books/?Db=pubmed&DbFrom=books&Cmd=Link&LinkName=books_pubmed_refs&IdsFromResult=4479376) Links to PubMed ### Similar articles in PubMed - [Review Comparing Two Ways to Manage Symptoms for Patients Who Have Chronic Migraine and Frequent Medication Use – The MOTS Trial](https://www.ncbi.nlm.nih.gov/pubmed/39432696)\[ 2022\] Review Comparing Two Ways to Manage Symptoms for Patients Who Have Chronic Migraine and Frequent Medication Use – The MOTS Trial Schwedt TJ, Dodick DW, Robert T, Hentz JG. 2022 Feb - [Transformed migraine and medication overuse in a tertiary headache centre--clinical characteristics and treatment outcomes.](https://www.ncbi.nlm.nih.gov/pubmed/15154858)\[Cephalalgia. 2004\] Transformed migraine and medication overuse in a tertiary headache centre--clinical characteristics and treatment outcomes. Bigal ME, Rapoport AM, Sheftell FD, Tepper SJ, Lipton RB. Cephalalgia. 2004 Jun; 24(6):483-90. - [Medication-Overuse Headache.](https://www.ncbi.nlm.nih.gov/pubmed/30844177)\[StatPearls. 2025\] Medication-Overuse Headache. Fischer MA, Jan A. StatPearls. 2025 Jan - [Prescription of Controlled Substances: Benefits and Risks.](https://www.ncbi.nlm.nih.gov/pubmed/30726003)\[StatPearls. 2025\] Prescription of Controlled Substances: Benefits and Risks. Preuss CV, Kalava A, King KC. StatPearls. 2025 Jan - [Review Medication-overuse headache.](https://www.ncbi.nlm.nih.gov/pubmed/22868543)\[Continuum (Minneap Minn). 2012\] Review Medication-overuse headache. Tepper SJ. Continuum (Minneap Minn). 2012 Aug; 18(4):807-22. 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Readable Markdown	## Continuing Education Activity According to the International Classification of Headache Disorders, 3rd edition, a medication overuse headache is a secondary chronic headache disorder. This condition is defined as headaches occurring for 15 or more days per month for 3 or more months in patients taking acute headache treatments too frequently. Medication overuse headaches are believed to occur when medications intended to relieve headaches are consumed frequently. Causal agents are varied and can include agents such as nonsteroidal anti-inflammatory drugs, triptans, ergot derivatives, and opioids, although any analgesic can potentially trigger the medication overuse headache. This activity describes issues associated with the overuse of medications intended to relieve headaches and the evaluation and management of medication overuse headaches, highlighting the role of the interprofessional team in managing headaches. Objectives: - Identify the epidemiology of medication overuse headaches. - Assess the pathophysiology of medication overuse headaches. - Develop the various treatment options for managing medication overuse headaches. - Implement interprofessional team strategies for improving care coordination and communication to advance the prevention and management of medication overuse headaches and improve patient outcomes. [Access free multiple choice questions on this topic.](https://www.statpearls.com/account/trialuserreg/?articleid=24890&utm_source=pubmed&utm_campaign=reviews&utm_content=24890) ## Introduction According to the International Classification of Headache Disorders, 3rd edition (ICHD-3), a medication overuse headache is a secondary chronic headache disorder. This condition is defined as headaches occurring for 15 or more days per month for 3 or more months in patients who use acute headache treatments too frequently.[\[1\]](https://www.ncbi.nlm.nih.gov/books/NBK470171/#article-24890.r1) Medication overuse headaches are believed to occur when medications intended to relieve headaches are consumed too frequently, leading to a secondary type of headache. This condition was previously called a rebound headache and is commonly observed in individuals with migraine; the excessive use of analgesics can transform episodic headaches into a chronic condition. The exact frequency of using the pain-relieving drug before developing the medication overuse headache varies and depends on the particular type of medication used. Causal agents include both simple and combination analgesics, triptans, ergot derivatives, and opioids, but potentially any painkiller can be the trigger. Patients who use simple analgesics and nonsteroidal anti-inflammatory drugs (NSAIDs) for 15 or more days, or who take combination analgesics—including ergots; barbiturates, such as butalbital; triptans; and opioids—for 10 or more days per month are considered to have a medication overuse headache. Medication overuse headaches are common in patients at risk of overusing acute medications. Individuals previously diagnosed with a primary headache disorder, particularly migraines or tension-type headaches, are at risk of developing this condition. Medication overuse headaches typically resolve once the overused medication is reduced or discontinued.[\[2\]](https://www.ncbi.nlm.nih.gov/books/NBK470171/#article-24890.r2)[\[3\]](https://www.ncbi.nlm.nih.gov/books/NBK470171/#article-24890.r3)[\[4\]](https://www.ncbi.nlm.nih.gov/books/NBK470171/#article-24890.r4)[\[5\]](https://www.ncbi.nlm.nih.gov/books/NBK470171/#article-24890.r5)[\[6\]](https://www.ncbi.nlm.nih.gov/books/NBK470171/#article-24890.r6) ## Etiology To diagnose medication overuse headaches according to the latest ICHD-3 criteria, the following three conditions must be fulfilled: - A headache must occur 15 or more days per month in patients with a previously diagnosed headache disorder. - A patient must have misused the acute headache medication for 3 or more months. - A headache is not attributable to another ICHD-3 headache condition. Medication overuse headaches are believed to occur when patients frequently use acute headache medications at the following rates—15 or more days per month for simple analgesics, such as acetaminophen and NSAIDs, and 10 or more days per month for ergotamine, triptans, opioids, or combination analgesics, such as butalbital, acetaminophen, or caffeine.[\[7\]](https://www.ncbi.nlm.nih.gov/books/NBK470171/#article-24890.r7)[\[8\]](https://www.ncbi.nlm.nih.gov/books/NBK470171/#article-24890.r8) The ICHD-3 states that when a combination of different headache medications is used, their combined frequency can lead to a medication overuse headache, even when the individual drugs are not overused separately. The most common group of patients with medication overuse headaches are those with chronic migraine, who account for about two-thirds of patients with medication overuse headaches. Patients with headaches respond to acute medications differently. The use of an inappropriate headache abortive medication or less effective medication can increase the frequency of medication consumption and lead to medication overuse headaches. For example, due to the differences in efficacy between acetaminophen 1000 mg (NNT=12) and ibuprofen 400 mg (NNT=7.2), a patient using acetaminophen typically requires more frequent dosages to manage their headache compared to those using ibuprofen. The timing of acute headache treatment also affects the development of medication overuse headaches. Patients start medications for acute headaches, especially migraine medications, too late, which reduces their effectiveness. This underuse of both acute and preventive medications has been shown to contribute to the progression of migraine and subsequent medication overuse headaches.[\[9\]](https://www.ncbi.nlm.nih.gov/books/NBK470171/#article-24890.r9) ## Epidemiology Medication overuse headaches are considered one of the more prevalent neurological disorders. The 2015 Global Burden of Disease study estimated its prevalence at 1% worldwide, affecting approximately 58.5 million people, which is lower compared to that of migraine and tension-type headaches. However, the same study ranked medication overuse headaches among the 20 most debilitating diseases. Medication overuse headaches occur relatively commonly in patients with chronic migraines, with about 32% of individuals in this group experiencing medication overuse headaches. Medication overuse headaches are believed to be more common in women, with a male-to-female ratio ranging from 2:1 to 5:1, and in those with low socioeconomic status.[\[10\]](https://www.ncbi.nlm.nih.gov/books/NBK470171/#article-24890.r10) ## Pathophysiology The exact mechanism of medication overuse headaches is unclear. However, it is hypothesized that medication overuse headaches result from the depletion of 5-HT due to the overuse of headache-abortive medications. This depletion leads to neuronal hyperexcitability in the cerebral cortex, which may result in cortical spreading depression, and the trigeminal system, which produces peripheral and central sensitization. The decrease in 5-HT levels leads to an increased release of calcitonin gene-related peptide from the trigeminal ganglia, which is involved in the subsequent sensitization of nociceptive trigeminal neurons.[\[11\]](https://www.ncbi.nlm.nih.gov/books/NBK470171/#article-24890.r11) Other studies have shown structural and functional brain changes in patients with medication overuse headaches. Morphometric magnetic resonance imaging has found increased gray matter volume in regions such as the midbrain, thalamus, and striatum. The midbrain gray matter volume changes resolved after removing the offending medication. The orbitofrontal cortical gray matter volume is lower in patients with medication overuse headaches, and a poor treatment response was observed.[\[12\]](https://www.ncbi.nlm.nih.gov/books/NBK470171/#article-24890.r12) PET scans of patients with medication overuse headaches reveal significant metabolic changes in various brain structures, most of which reverse upon the withdrawal of analgesic medication, except for persistent hypometabolism observed in the orbitofrontal area. This area is known to be involved in drug dependence and is hypothesized to be a risk factor for subsequent relapse in analgesic overuse and recurrent medication overuse headaches.[\[13\]](https://www.ncbi.nlm.nih.gov/books/NBK470171/#article-24890.r13)[\[14\]](https://www.ncbi.nlm.nih.gov/books/NBK470171/#article-24890.r14)[\[13\]](https://www.ncbi.nlm.nih.gov/books/NBK470171/#article-24890.r13) ## History and Physical Clinical presentation of medication overuse headaches varies among patients and may even change over time in the same individual. Patients may experience an increase in the frequency of a pre-existing headache or the development of a new type of headache. Since no specific tests exist for diagnosing this condition, the diagnosis relies on evaluating headache frequency, quantity, and the type and frequency of acute medication use.[\[15\]](https://www.ncbi.nlm.nih.gov/books/NBK470171/#article-24890.r15) Although pain location and quality are nonspecific in medication overuse headaches, certain general features are commonly observed in affected patients, including: - The headaches are typically episodic. - Frequent acute medication consumption depends on the type of abortive medication used. Generally, the threshold for developing medication overuse headaches is 15 or more days for acetaminophen and NSAIDs and 10 or more days for triptans, ergots, opioids, combination analgesics, and multiple drug classes.[\[16\]](https://www.ncbi.nlm.nih.gov/books/NBK470171/#article-24890.r16) - Neck pain is common and often mistaken for a cervicogenic headache, which in turn tends to be resistant to cervicalgia-appropriate treatments. - Typically occurs in the morning, presumed related to withdrawal occurring during sleep. - Poor sleep quality. - Autonomic symptoms, such as nasal congestion, rhinorrhea, and gastrointestinal disturbance, are more frequent with overused opioids. - Comorbid anxiety and depression. - All headache treatments are generally less effective in cases of medication overuse headaches; their efficacy improves after medication withdrawal. ## Evaluation There are currently no specific biomarkers or studies to differentiate or confirm medication overuse headaches. The diagnosis is entirely clinical and requires careful attention, as overlooking this condition can lead to its progression and worsening over time. ## Treatment / Management Education is the most crucial first step for patients with medication overuse headaches. Patients must understand and be aware of the headache issues related to their symptoms and misuse of headache remedies. Mindfulness has been shown to be an effective treatment strategy.[\[17\]](https://www.ncbi.nlm.nih.gov/books/NBK470171/#article-24890.r17) In addition to education, the standard treatment of medication overuse headaches involves weaning the patient off the overused acute headache medication while simultaneously focusing on preventative treatment. Several studies show that complete discontinuation of overused acute medication yields the best outcomes compared to continuing the same acute medication with restricted frequency. Patients can be prescribed a new acute medication from a different class. Discontinuation can be achieved either abruptly (cold turkey) or gradually over several weeks. Preventative treatment can include prophylactic medication or nonpharmaceutical treatments, such as cognitive behavioral therapy, biofeedback, relaxation training, and lifestyle modification with trigger avoidance.[\[18\]](https://www.ncbi.nlm.nih.gov/books/NBK470171/#article-24890.r18)[\[19\]](https://www.ncbi.nlm.nih.gov/books/NBK470171/#article-24890.r19)[\[20\]](https://www.ncbi.nlm.nih.gov/books/NBK470171/#article-24890.r20) Educating patients and their families about the importance of limiting acute medication use is vital in preventing medication overuse headaches. Initial worsening of a headache within the first few days of weaning is relatively common. Withdrawal symptoms are believed to last up to 10 days, then eventually followed by improvement in medication overuse headaches.[\[14\]](https://www.ncbi.nlm.nih.gov/books/NBK470171/#article-24890.r14) Weaning patients off medication overuse headache-related medication can be done in an outpatient or an inpatient setting. Most cases can be managed in the outpatient setting, mainly through educating patients to cut down on their acute medication use. Addressing and treating comorbid psychiatric conditions, especially anxiety and depression, which are often associated with medication overuse headaches, are crucial. However, without enhancing the boosting effects, anxiolytic medication may contribute to the persistence of headaches. Following successful weaning, about 50% of patients relapse after 5 years; thus, it is essential to have the patient follow-up regularly. Once the patient's medication overuse headache has resolved, tapering them off the preventative medication may be considered. There are no specific guidelines, but some clinicians suggest tapering prophylactic medications after 1 year.[\[21\]](https://www.ncbi.nlm.nih.gov/books/NBK470171/#article-24890.r21)[\[22\]](https://www.ncbi.nlm.nih.gov/books/NBK470171/#article-24890.r22) ## Differential Diagnosis A medication overuse headache occurs in patients with an episodic primary headache; thus, chronic versions of an episodic headache are one of the main differentials. The most common differential diagnosis of medication overuse headache is chronic migraine. Secondary headaches should be ruled out with the guidance of the patient's clinical presentation and the aid of all the necessary tests, especially when the features of the original episodic headache are different from their chronic counterparts.[\[23\]](https://www.ncbi.nlm.nih.gov/books/NBK470171/#article-24890.r23)[\[24\]](https://www.ncbi.nlm.nih.gov/books/NBK470171/#article-24890.r24) ## Prognosis A tailored regime yields excellent long-term results; however, the estimated relapse rate is about 30% within 6 months and 50% following a 5-year period.[\[25\]](https://www.ncbi.nlm.nih.gov/books/NBK470171/#article-24890.r25) ## Complications Complications associated with medication overuse headaches include additional symptoms linked to more severe and chronic forms of primary headache disorders. These symptoms include nausea, anxiety, irritability, asthenia, restlessness, difficulty concentrating, problems with memory, and depression.[\[26\]](https://www.ncbi.nlm.nih.gov/books/NBK470171/#article-24890.r26) ## Deterrence and Patient Education Education plays a crucial role in treating medication overuse headaches. Patients must understand the underlying causes of their headaches to adhere to changes in their medication regimen, which typically involves restricting their medication use. Depending on the drug used, patients may need to either discontinue the drug immediately or gradually taper the dose. ## Pearls and Other Issues Healthcare professionals contend that frequent use of acute headache medications may indicate poorly controlled headaches and not necessarily the cause. This idea stems from evidence that not all patients improve when they stop taking headache-relieving medications. Instead of primarily blaming analgesic medication overuse as the reason for the increase in headache frequency, clinicians must be cautious in treating these patients and not overlook those in whom headaches are simply poorly controlled. Some studies suggested that other substances, such as the regular use of tranquilizers or other recreational substances abused in the general population, should be considered in conjunction with analgesics. ## Enhancing Healthcare Team Outcomes The diagnosis and management of medication overuse headaches are complex and best performed by an interprofessional team that includes clinicians, specialists, nursing staff, and pharmacists. Educating the patient and their family on the importance of limiting acute medication use is vital in preventing medication overuse headaches. The underlying psychiatric condition must be addressed, and a referral to a mental health professional can be helpful. All interprofessional team members are responsible for contributing from their areas of expertise, documenting any change in patient status, and communicating their observations with other team members as appropriate so therapeutic interventions can occur if necessary. Following successful weaning, about 50% of the patients relapse after 5 years, so regular follow-up is crucial. Once the patient's medication overuse headache has resolved, tapering them off the preventative medication may be considered. There are no specific guidelines, but some professionals suggest tapering prophylactic medication after 1 year. ## References 1\. Headache Classification Committee of the International Headache Society (IHS) The International Classification of Headache Disorders, 3rd edition. Cephalalgia. 2018 Jan;38(1):1-211. \[[PubMed: 29368949](https://pubmed.ncbi.nlm.nih.gov/29368949)\] 2\. Limmer AL, Holland LC, Loftus BD. Zonisamide for Cluster Headache Prophylaxis: A Case Series. Headache. 2019 Jun;59(6):924-929. \[[PubMed: 31038740](https://pubmed.ncbi.nlm.nih.gov/31038740)\] 3\. Mose LS, Pedersen SS, Jensen RH, Gram B. Personality traits in migraine and medication-overuse headache: A comparative study. Acta Neurol Scand. 2019 Aug;140(2):116-122. \[[PubMed: 31038726](https://pubmed.ncbi.nlm.nih.gov/31038726)\] 4\. Young NP, Philpot LM, Vierkant RA, Rosedahl JK, Upadhyaya SG, Harris A, Ebbert JO. Episodic and Chronic Migraine in Primary Care. Headache. 2019 Jul;59(7):1042-1051. \[[PMC free article: PMC6625910](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6625910/)\] \[[PubMed: 31032913](https://pubmed.ncbi.nlm.nih.gov/31032913)\] 5\. Sandoe CH, Lay C. Secondary Headaches During Pregnancy: When to Worry. Curr Neurol Neurosci Rep. 2019 Apr 22;19(6):27. \[[PubMed: 31011857](https://pubmed.ncbi.nlm.nih.gov/31011857)\] 6\. Micieli A, Kingston W. An Approach to Identifying Headache Patients That Require Neuroimaging. Front Public Health. 2019;7:52. \[[PMC free article: PMC6428716](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6428716/)\] \[[PubMed: 30931292](https://pubmed.ncbi.nlm.nih.gov/30931292)\] 7\. Grazzi L, D'Amico D. Chronic migraine and medication overuse: which strategy for a complex scenario. Neurol Sci. 2019 May;40(Suppl 1):175-176. \[[PubMed: 30906961](https://pubmed.ncbi.nlm.nih.gov/30906961)\] 8\. Turner DP, Lebowitz AD, Chtay I, Houle TT. Headache Triggers as Surprise. Headache. 2019 Apr;59(4):495-508. \[[PMC free article: PMC6521840](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6521840/)\] \[[PubMed: 30919414](https://pubmed.ncbi.nlm.nih.gov/30919414)\] 9\. Rattanawong W, Rapoport A, Srikiatkhachorn A. Medication "underuse" headache. Cephalalgia. 2024 Apr;44(4):3331024241245658. \[[PubMed: 38613233](https://pubmed.ncbi.nlm.nih.gov/38613233)\] 10\. Kulkarni GB, Mathew T, Mailankody P. Medication Overuse Headache. 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Forebrain delta opioid receptors regulate the response of delta agonist in models of migraine and opioid-induced hyperalgesia. Sci Rep. 2020 Oct 19;10(1):17629. \[[PMC free article: PMC7573615](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7573615/)\] \[[PubMed: 33077757](https://pubmed.ncbi.nlm.nih.gov/33077757)\] 14\. Sebastianelli G, Casillo F, Abagnale C, Di Renzo A, Ziccardi L, Parisi V, Di Lorenzo C, Serrao M, Coppola G. Neurophysiological Effects of Withdrawal from Acute Overused Medications in Chronic Migraine with Medication-Overuse Headache. J Clin Med. 2024 Dec 09;13(23) \[[PMC free article: PMC11642649](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11642649/)\] \[[PubMed: 39685947](https://pubmed.ncbi.nlm.nih.gov/39685947)\] 15\. Scher AI, Rizzoli PB, Loder EW. Medication overuse headache: An entrenched idea in need of scrutiny. Neurology. 2017 Sep 19;89(12):1296-1304. \[[PubMed: 28821684](https://pubmed.ncbi.nlm.nih.gov/28821684)\] 16\. Gosalia H, Moreno-Ajona D, Goadsby PJ. Medication-overuse headache: a narrative review. J Headache Pain. 2024 May 31;25(1):89. \[[PMC free article: PMC11140994](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11140994/)\] \[[PubMed: 38816828](https://pubmed.ncbi.nlm.nih.gov/38816828)\] 17\. Wells RE, O'Connell N, Pierce CR, Estave P, Penzien DB, Loder E, Zeidan F, Houle TT. Effectiveness of Mindfulness Meditation vs Headache Education for Adults With Migraine: A Randomized Clinical Trial. JAMA Intern Med. 2021 Mar 01;181(3):317-328. \[[PMC free article: PMC7737157](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7737157/)\] \[[PubMed: 33315046](https://pubmed.ncbi.nlm.nih.gov/33315046)\] 18\. Ferini-Strambi L, Galbiati A, Combi R. Sleep disorder-related headaches. Neurol Sci. 2019 May;40(Suppl 1):107-113. \[[PubMed: 30906963](https://pubmed.ncbi.nlm.nih.gov/30906963)\] 19\. Barmherzig R, Kingston W. Occipital Neuralgia and Cervicogenic Headache: Diagnosis and Management. Curr Neurol Neurosci Rep. 2019 Mar 19;19(5):20. \[[PubMed: 30888540](https://pubmed.ncbi.nlm.nih.gov/30888540)\] 20\. Russell MB. Epidemiology and management of medication-overuse headache in the general population. Neurol Sci. 2019 May;40(Suppl 1):23-26. \[[PubMed: 30887240](https://pubmed.ncbi.nlm.nih.gov/30887240)\] 21\. Arca KN, Halker Singh RB. The Hypertensive Headache: a Review. Curr Pain Headache Rep. 2019 Mar 14;23(5):30. \[[PubMed: 30874912](https://pubmed.ncbi.nlm.nih.gov/30874912)\] 22\. Bottiroli S, Galli F, Viana M, De Icco R, Bitetto V, Allena M, Pazzi S, Sances G, Tassorelli C. Negative Short-Term Outcome of Detoxification Therapy in Chronic Migraine With Medication Overuse Headache: Role for Early Life Traumatic Experiences and Recent Stressful Events. Front Neurol. 2019;10:173. \[[PMC free article: PMC6416203](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6416203/)\] \[[PubMed: 30899242](https://pubmed.ncbi.nlm.nih.gov/30899242)\] 23\. Saengjaroentham C, Strother LC, Dripps I, Sultan Jabir MR, Pradhan A, Goadsby PJ, Holland PR. Differential medication overuse risk of novel anti-migraine therapeutics. Brain. 2020 Sep 01;143(9):2681-2688. \[[PMC free article: PMC7523700](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7523700/)\] \[[PubMed: 32810212](https://pubmed.ncbi.nlm.nih.gov/32810212)\] 24\. Lucas C, Diener HC. The dependence scale: an easy tool to detect chronic daily headache with medication overuse? J Neurol Neurosurg Psychiatry. 2009 Jul;80(7):704. \[[PubMed: 19531683](https://pubmed.ncbi.nlm.nih.gov/19531683)\] 25\. Munksgaard SB, Madsen SK, Wienecke T. Treatment of medication overuse headache-A review. Acta Neurol Scand. 2019 May;139(5):405-414. \[[PubMed: 30710346](https://pubmed.ncbi.nlm.nih.gov/30710346)\] 26\. Dodick D, Freitag F. Evidence-based understanding of medication-overuse headache: clinical implications. Headache. 2006 Nov;46 Suppl 4:S202-11. \[[PubMed: 17078852](https://pubmed.ncbi.nlm.nih.gov/17078852)\] Disclosure: Dmitri Aleksenko declares no relevant financial relationships with ineligible companies. Disclosure: Forshing Lui declares no relevant financial relationships with ineligible companies. Disclosure: Juan Carlos Sánchez-Manso declares no relevant financial relationships with ineligible companies.
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