Medication-overuse Headache (MOH)

Article Author:
Michelle Fischer

Article Editor:
Arif Jan

Editors In Chief:
Evelyn Metz
Julie Sewell
Aditya Arya

Managing Editors:
Avais Raja
Orawan Chaigasame
Carrie Smith
Abdul Waheed
Khalid Alsayouri
Trevor Nezwek
Radia Jamil
Patrick Le
Anoosh Zafar Gondal
Saad Nazir
William Gossman
Hassam Zulfiqar
Steve Bhimji
John Shell
Matthew Varacallo
Heba Mahdy
Ahmad Malik
Sarosh Vaqar
Mark Pellegrini
James Hughes
Beata Beatty
Nazia Sadiq
Hajira Basit
Phillip Hynes
Tehmina Warsi

3/1/2019 3:01:02 PM


Medication-overuse headache (MOH) is a common neurologic disorder with enormous disability and suffering and plays a significant role in the transformation from episodic to chronic headache disorders. Multiple terms have been used to describe MOH such as analgesic rebound headache, drug-induced headache or a medication-misuse headache. Patients with established primary headache disorders like migraine or tension-type headaches excessively overuse medication for their acute headache and inadvertently increase the frequency and intensity of their headache.  In this manner, a vicious cycle of further drug consumption and increased headache frequency develops transforming the treatment for their headache to the actual cause of their disease (MOH). Patients prone to headaches who take analgesics for other conditions can also develop MOH.[1][2]

Recognition of MOH was as early as in the 1930s when physicians observed prolongation of headache associated with ergotamine-overuse.[3] In the 1970s and 1980s, physicians observed its association with analgesics such as barbiturates, codeine, and combination analgesics as well and also noticed a reduction in headache frequency with stopping drugs. For a short time, it was referred to as transformed or an evolutive migraine.[4] The first edition of the International Classification of Headache Disorders (ICHD) in 1988 first defined the disorder calling it a drug-induced headache that was a “headache induced by chronic substance use or exposure.”[5] MOH was first introduced in the second edition of ICHD (2004) with multiple subtypes dependent on offending medicine,  such as ergotamines, triptans, opioids, etc.[6]


Medication overuse headache currently classifies as a secondary headache or chronic headache syndrome in the latest version of ICHD-3 (2018) under subsection 8.2 as a chronic headache disorder secondary to a pre-existing headache syndrome.[7] The specific subtype of MOH is dependent upon the medicine involved.  Overarching criteria are that (1) a headache is occurring on greater than or equal to 15 days per month for a patient with a pre-existing headache disorder (2) regular medication overuse for greater than 3 months of one or more drugs that can be taken for acute and/or symptomatic treatment of a headache and (3) Not better accounted for by another ICHD-3 diagnosis.  If multiple drugs are overused, all applicable/multiple codes should be used.  There are no clinical characteristics defined as the headache typically resembles the pre-existing headache syndrome. The general rule is that the MOH resolves upon cessation of the medication. In this manner, two diagnoses are made, first the primary headache syndrome and second the MOH. It is no longer a requirement for the diagnosis that headache pattern returns to previous within two months of stopping the offending drug. 

As the name implies, chronic medication overuse is the most significant risk factor for the development of MOH with each of the classes of analgesics carrying a different risk profile.  The risk from lowest to highest is:  triptans/ergotamine, single analgesic agents (NSAIDs, acetaminophen), and combination analgesics containing opiates or barbiturates.  There have been observations that combination analgesics particularly those containing opioids and/or barbituates have a two-fold increase relative risk for MOH. 

NSAIDs may have a protective effect from MOH in patients with ten headache days or less per month.[8]


Medication overuse headache has a true prevalence that is unknown partly resulting from various changes in diagnostic criteria, but estimates are in the range from 0.5% to 2.6% in the general population.  Higher rates have been reported in Russia (7.6%) and Iran (4.6%), places where it is felt that medication overuse is more prevalent.[9]  In some studies from specialized headache centers, the prevalence of MOH in patients with chronic daily headaches has been reported anywhere from 11% to 70%, much higher than the general population. In approximately 80% of MOH patients, migraine is the underlying primary headache disorder with the overwhelming remaining having tension-type or post-traumatic headaches.  MOH most commonly affects those age 30 to 50 years with a female to male predominance of 3 to 4 to 1.   Interestingly enough, between 21% and 52% of pediatric patients and 35% of the elderly over the age of 64 met criteria for MOH.  Some studies in Europe have reported increased prevalence in first-generation migrants, and the feeling was that a potential explanation for this was multi-factorial but likely included socioeconomic class, genetic predisposition, and cultural reasons.  As MOH is a worldwide problem, experts surmise that economic, psychological and physical disability all factor into the etiology of this disease.  In 2016 Global Burden of Disease (GBD) listed migraine as the second largest cause of disability likely because MOH was considered an emanation of migraine and tension headache.[10]

Main Risk Factors for MOH with Odds Ratio (OR)[11][12][13]:

  • Demographic
    • Age (less than 50 years)--1.8
    • Female--1.9
    • Low educational level--1.9
  • Self-reported complaints
    • Chronic musculoskeletal complaints--1.9
    • Gastrointestinal complaints--1.6
    • Anxiety or depression--4.7
  • Lifestyle
    • Smoking--1.8
    • Physical inactivity--2.7
    • Metabolic syndrome--5.3
    • High daily caffeine intake (greater than 540mg versus less than 240mg)--1.4
  • Medication
    • Tranquilizers--5.2
    • Aspirin--0.5
    • Ibuprofen--0.7
    • Opioids--2.3

Of those patients with MOH, dependency-like behavior presented more often in those that overuse opioids and triptans than aspirin or ibuprofen.  MOH can be associated with substance-related disorder spectrum as it is believed they share common neurobiological pathways.[14] Data like these support a biological predisposition as another significant risk factor for MOH. Of all headache types, migraine is the one most commonly associated with MOH and occurs in approximately 80% of patients.[15] Patients with higher headache frequency at baseline are also at higher risk for MOH.  It is unknown if the high headache frequency leads to more drug consumption and thus MOH or if patients with higher frequency attack are more prone to MOH.  Another study found a threefold risk of MOH if family history of MOH or substance abuse (drug or alcohol).[16] Several trials have demonstrated that frequent and often multiple psychiatric mood disorders such as anxiety and depression exist in patients with MOH.[17] Some trials interestingly found that 40% of MOH patients actually met criteria for depression and upwards of 58% for anxiety.[18] It remains unclear if psychiatric comorbidities are risk factors or just the consequences of MOH.  The 2011 Hagen longitudinal study found that patients with a tension-type headache had the highest incidence of psychiatric comorbidities.  Another study found patients with MOH have a higher susceptibility towards drug dependency and obsessive-compulsive disorder (OCD).[16] 


The pathophysiology of MOH is not well understood, but studies have demonstrated that central sensitization likely plays a major role.[19]  Since patients with migraine or tension-like headaches are prone to developing MOH, the theory is that similar physiological mechanisms may be involved.  The condition exhibits both functional and structural changes in the central nervous system (CNS) particularly the hippocampal periaqueductal gray area, posterior cingulate cortex thalamus, cerebellum, orbitofrontal cortex (OFC) and the mesocorticolimbic reward system.[20][21]  Also found were changes in the serotonergic neuromodulatory system, upregulation of vasoactive and pro-inflammatory mediators increases susceptibility to cortical spreading depression, central sensitization and an increase in nociceptive sensory fields.[22]  Some studies have theorized a potential genetic risk as the etiology for the development of MOH.  One such model is the renin-angiotensin system known to have an active role in regulating neural plasticity.[23]

The thinking is that the insertion/deletion polymorphism in the gene that encodes angiotensin-converting enzyme (ACE) increases an individual’s susceptibility to MOH.  ACE is a key enzyme in regulating blood pressure, but in the brain, it interacts with monoaminergic synaptic transmission thereby contributing to dependence behavior.  ACE polymorphisms seen in MOH patients have been demonstrated to influence sensitization and habituation patterns.  Other potential polymorphisms are brain-derived neurotrophic factor (BDNF), catechol-O—methyltransferase (COMT) and serotonin transporter (SERT).[24][25][26]  All of these lead to disturbances in the normal brain pathway neurotransmitters making patients more susceptible to dependence, behavioral disorders, substance abuse, pain disorders, and several neuropsychiatric disorders.   

Animal studies have also demonstrated that pain medications alone can cause altered neurotransmitter metabolism especially the serotoninergic and endocannabinoid systems.[27] Several human studies have shown hypersensitization and hyperresponsiveness of the cerebral cortex suggesting that the brain of those suffering from MOH are “locked” in a pre-excitation state.  In fact, all MOH patients exhibited increased somatosensory evoked potential (SEP) amplitude after stimulation as well as lack of habituation after further stimulation.[28] After drug discontinuation, a slow progression back to normal sensory processing was observed in most patients and within most areas of the brain.  The primary force leading to MOH related structural and functional properties of the brain seem to be prolonged exposure to pain medications.  All pain medications can cause MOH, but some drug classes can cause it faster or with shorter overuse. Therefore it is believed from evidence from multiple studies that MOH causes changes in the central nervous system specifically in pain processing and dependence networks, sensitization and receptor density all of which help to explain the clinical features of the disease.

History and Physical

As always, detailed history with particular emphasis on evaluating headache is essential. Equally important is the detailed medication history and history of substance abuse.  To be considered for a diagnosis of MOH, a patient must have a headache for 15 or more days monthly in a patient with an established diagnosis of a headache disorder such as migraine or tension-type.  Additionally, they must be utilizing one or more symptomatic medications regularly (10 to 15 days per month depending on the type of drug consumed) for over 3 months.  The headache characteristics are usually typical for their primary headache types such as migraine or tension although they are often more intense and frequent. Evolution towards MOH is substance-specific occurring faster in those that overuse triptans, opiates, and combination analgesics than those that overuse simple analgesics. 

The most common headache diagnoses before the evolution of MOH are migraines (65%), tension-type headache (27%) and mixed/other headaches (8%).[29]  Note that the transition from episodic to MOH is typically gradual in onset with patients noting an increase in their headache intensity and frequency. Patients typically describe their usual headache but caution is advisable as features of their headache can change over time.  Most patients with MOH (90%) utilize multiple different medications for relief.[29]  Patients often report morning headaches and neck pain which may be the result of overnight drug withdrawal or poor sleep quality.[30]

The central sensitization causes by MOH can lead to skin hypersensitivity and the expansion of their headache.  Autonomic and gastrointestinal symptoms such as a runny nose, tearing, nausea, vomiting and diarrhea can accompany their headache.  Physical examination is typically nonfocal with no neurologic deficits. A false-positive diagnosis must be excluded by obtaining a detailed history and physical examination including headache type, frequency and drug use to rule out any secondary headache syndromes that may require different management.


Remember it is the frequency of a headache and not the quality or intensity that makes the diagnosis of MOH.  Unless there are concerning clinical features in the patient's history or physical examination, there are no confirmatory nor necessary laboratory, radiographic or other tests required to make the diagnosis of MOH.

Diagnosis of medication-overuse headache (MOH) according to ICHD-3, must meet criteria A-C for the diagnosis of MOH:

  • Headache on 15 or more days per month AND a pre-existing headache disorder
  • Overuse of acute and/or symptomatic headache drugs for over 3 months (Regular intake of drugs on greater than or equal to 10 days/month for ergotamines, triptans, opioids, and combination analgesics and on greater than or equal to 15 days per month for acetaminophen, ASA and NSAIDs)
  • No better explanation by another ICHD-3 diagnosis  

Medication overuse headache by drug class and duration of headache[31]:

  • Ergotamine-->10 days/month for over 3 months
  • Triptan-->10 days/month for over 3 months
  • ASA-->15 days/month for over 3 months
  • NSAIDs-->15 days/month for >3 months
  • Acetaminophen/paracetamol-->15 days/month for over 3 months
  • Opioids-->10 days/month for over 3 months
  • Combination analgesics-->10 days/month for over 3 months
  • Multiple drug classes-->10 days/month for over 3 months

Treatment / Management

Prevention:  MOH is felt to be a preventable disease; therefore, the emphasis should is on educating patients on the importance of appropriate medication administration and the risks not only of its side effects but also the potential development of chronic headache with excessive medication use is essential.[32]  The thinking is that only 8% of patients demonstrate knowledge that overuse of all types of headache medication, including those readily available over the counter, could lead to the development of MOH.  

MOH requires a multi-step treatment approach but typically entails (1) withdrawal of the overused medication, (2) treatment of withdrawal symptoms or rescue therapy, and (3) initiation of preventative therapy if desired and (4) finally alternative symptomatic medication for future headaches.  There currently is not enough high powered evidence from randomized trials to indicate which is the best or most effective method of treatment for MOH to date. 

Drug Withdrawal Phase:  The clinician must first determine if the patient can be managed safely as an outpatient or if they require inpatient hospitalization for close monitoring during the drug withdrawal phase.  Several studies have demonstrated that advice alone might be appropriate for those patients who do not have major psychiatric comorbidities and overuse triptans or simple analgesics.  Fortunately, this can be managed by the patient’s primary care provider in most cases.  The Brief Intervention for Medication-Overuse Headache (BIMOH) study found that brief intervention by patient’s own physician on the education of medication overuse had lasting and impactful results with 50% of headaches resolved within 3 months and 63% in 6 months.[33]

A classification system for MOH was created by Saper and Lake to help stratify these patients.[34]  MOH Type I are those patients who do not have behavioral conditions and do not overuse opioids or barbiturates.  These patients are more simple and are manageable in the outpatient setting with a clear rescue medication program.  MOH Type 2 patients may need inpatient therapy.  They are more complex and suffer from behavioral conditions and because they chronically use opioids and barbiturates are more likely to have withdrawal symptoms, emotional and sleep problems and experience more pain during the withdrawal phase. The 2011 European Federation of Neurological Societies (EFNS) state that withdrawal therapy is the best treatment for MOH.[35][36]  The rate of removal of the drug, whether it is rapid or tapered, has not been studied to determine the most effective method, but the consensus is that a rapid withdrawal leads to a more rapid resolution.  Drugs that are known to have potentially significant and life-threatening withdrawal symptoms, such as barbiturates, opioids or benzodiazepines, should have a tapered withdrawal.  Typical withdrawal symptoms are worsening headache, restlessness, anxiety, insomnia, nervousness, nausea, vomiting, tachycardia or hypotension.  Some symptoms may last up to 4 weeks but typically last 2 to 10 days.[35] These patients do not necessarily require management by a neurologist during the withdrawal phase as a study from 2009 demonstrated similar outcomes with primary care provider management.[37]  

Withdrawal Treatment or Rescue Medication Phase: To help minimize a patient's withdrawal symptoms and maximize comfort during this phase several medication therapies have demonstrated usefulness.  Keep in mind that the offending drug should not be an option.  Several NSAIDs have been trialed and demonstrated effective such as naproxen, indomethacin, and ketorolac.[38][39] Tizanidine is beneficial as an adjunct to NSAID therapy.[40] Steroid therapy, in several currents studies, has demonstrated minimal to no effect on MOH withdrawal symptoms including fewer headache hours.[41][42][43] Several antiemetics and neuroleptics have proven useful during this phase including prochlorperazine,[44] diphenhydramine, promethazine, metoclopramide, and chlorpromazine.[39]  Infusions with dihydroergotamine (DHE) may be necessary in more complex cases. 

The "Raskin protocol" is one such regimen that compared intravenous DHE and metoclopramide every 8 hours versus diazepam in patients with MOH and it demonstrated that DHE was beneficial (89% headache free in 48 hours and 71% at 16 months) during the detoxification phase of MOH,[45] however it should not be utilized in patients with vascular disease.[30]  Lidocaine infusions may be helpful in those with vascular disease.[46]. A retrospective study by Williams demonstrated 90% of MOH patients with a history of analgesic abuse including opioids had headache improvement, 97% withdrew the overused drug, and 70% had sustained benefits at 6 months. Valproate showed improvement in 80% of patients with MOH in a small study with good patient tolerance.[47]  Intravenous hydration, antiemetics, NSAIDs, and magnesium are also helpful during the withdrawal phase.[48]  During detoxification, those Type 2 MOH more complex patients that have overused narcotics, barbiturates, and tranquilizers may require long-acting opioids, phenobarbital, and clonidine while in transition.

Prophylaxis Therapy Phase: Consensus agrees that the most appropriate and effective choice for treatment of MOH is the acute withdrawal of painkilling drugs, but debate exists as to when and whether preventative medications should be utilized.  A guideline from the European Federation of Neurological Sciences recommends the abrupt discontinuation of the overused medication and if started prophylactic therapy initiation just before or at the time of drug discontinuation with close regular follow-up. If used, preventive therapies are started at low doses when MOH treatment begins, then titrated up with time with the choice of treatment depends upon previous drugs used, patient preferences, the type of primary headache disorder, comorbidities and the side effect profile.[49]  To date, therapy with beta-blockers, calcium channel blockers, tricyclic antidepressants, and anticonvulsants have all been utilized.[39]  In studies, topiramate in studies was beneficial in patients with MOH but is more effective in patients with chronic migraine.[50][51]  In the PREEMPT trials for chronic migraine, onabotulinumtoxinA was studied.  A number of the patients in the trial had MOH, and subgroup analysis performed on those patients reported benefit in reducing headache days, frequency and severity but this study did not include patients who overused opioids.[52][53][54]  The COMOESTAS project demonstrated that the combination of detoxification and prophylaxis of MOH patients decreased disability, depression, and anxiety.[18]  This group developed an evidence-based treatment protocol and at the end of their trial, 66% of MOH patients no longer overused medications and 47% reverted back to episodic headaches.[55]  Not surprisingly when comparing inpatient versus outpatient programs, the dropout rate was higher in the outpatient setting. 

The Consensus protocol for the treatment of MOH from Tassorelli et al. is as follows[55]:

Use a headache diary

  • STEP 1:  Withdraw overused medication (day 1)
  • STEP 2A:  Detoxification and rescue therapy (day 1 to 7)
    • Antiemetics such as:
      • Metoclopramide 10 mg IM or PO three times daily or equivalent (chlorpromazine, prochlorperazine, domperidone, levomepromazine)
    • Analgesics for a maximum of 3 days within the first week such as (Do not use rescue medication that is the same class of drug as previously overused):
      • Acetaminophen 1000 mg PO, PR or IV
      • Naproxen 500mg PO
  • STEP 2B:  Preventative treatment (day 1 to 7), optional but chosen based on side effects, co-morbid conditions, previous therapeutic experiences from the following:
    • Beta-blockers--propanolol 80-240 mg/day, atenolol 75-200 mg/day, metoprolol 100-200 mg/day
    • Valproic acid 500-1500 mg/day
    • Topiramate 50-200 mg/day
    • Flunarizine 5-10 mg/day
    • Amitriptyline 20-100 mg/day
    • Candesartan 8-16 mg/day
  • STEP 3:  Headache symptomatic medications (from day 8 and on)
    • Take headache medications at a maximum of 2 days per week.  It should not with the same class of drug previously overused and based upon the patient's medical history, headache characteristics and past therapeutic experiences.

Prevention of relapse in MOH is not well studied, but withdrawal strategies and preventative therapies do not appear to affect prognosis or relapse rates.[55] According to a recent review of the treatment of MOH by Chiang et al. in 2016, the authors felt that considering the current evidence on the treatment of MOH and taking into account the systemic toxicity of overusing headache medications, that discontinuation of the medication was the recommendation, with the addition of preventative medication. This approach led to a better outcome than discontinuation alone, but more studies are necessary to choose the best treatment strategy. 

Differential Diagnosis

The differential diagnosis of MOH would include any form of chronic daily headache whether it is a primary or secondary headache diagnosis including migraine, tension-type, and cluster.  Always ask patients about a history of head trauma, and if a patient’s history or physical examination causes concern, then appropriate diagnostic testing should be performed to rule out the possibility of a severe medical or neurologic condition.  Some differentials that should be under consideration are venous sinus thrombosis, subdural hematoma, carbon monoxide poisoning, brain tumors, hydrocephalus, and idiopathic intracranial hypertension.


Overuse of acute therapy can lead to a poor prognosis of chronic headache and lower quality of life by itself.[56]  The key to MOH treatment is patient motivation.[39]  Outcomes for MOH patients withdrawing from acute drug overuse have had reports in multiple studies with a generally accepted success rate of greater than 50% reduction from baseline headache frequency.  Rates of successful withdrawal have been reported in around 50 to 70% of MOH patients after 1 year.[57]  A good predictor for long-term success is retaining withdrawal after 1 year.[58][59]  Relapse rates after 6 years range between 40 to 50%.[60]  A successful withdrawal phase leads to a better response for prophylactic treatment even in those patients with little to no improvement in headache frequency.[36]  Several predictors for relapse have been documented such as tension-type headache, longer duration of regular intake, a high number of acute treatments, no improvement after 2 months of withdrawal, smoking, and alcohol use and return to overused drugs[60][61][62][63][29]  Triptan overuse has a lower relapse rate while combined drug therapy has a higher relapse rate.[64][60]  Finally, codeine-containing drugs and patient-reported poor sleep quality, and high body pain are probable predictors for poor 1-year outcomes.[37] Adding behavioral therapy to the treatment algorithm can greatly reduce the relapse rates for MOH.  In this particular study, 42% of patients had a relapse of headache at 3 years, but only 12.5% reverted when coupled with behavioral therapy.[65]


Side effects from the medication including dependence and toxicity as well. 


Neurology and or psychiatry consultations can be sought when necessary. 

Deterrence and Patient Education

Patients with MOH will fair better if their comorbidities such as mood disorders, obesity, smoking or inactivity are also addressed and continual support is offered in the form of education, patient monitoring, and behavioral therapies. MOH awareness in the general public should be a goal as a study from 2014 demonstrated that 77% of undergraduate students were not aware of the existence of MOH, and after learning about MOH, 83% of the students felt there should be warnings about MOH on medication bottles and 80% after learning about MOH would reduce analgesic consumption.[66]

Enhancing Healthcare Team Outcomes

 MOH is a common and worldwide problem with a prevalence of 1% in the general population but accounts for approximately 11 to 70% in those with chronic daily headaches, often under-recognized and unfortunately correlate with a significant negative impact on the patient's quality of life. That opiates and combination analgesics carry an increased risk for MOH needs to be recognized. Among the multiple risk factors for the development of MOH, some are modifiable and require attention and action. Anxiety and depression are common comorbidities, and up to 50% of patients show dependence-type behaviors like tolerance or inability to control pain medication utilization. 

Treatment trials are still needed to determine the best evidence-based approach for helping these patients break their vicious headache cycle, but intervention will require patient counseling, detoxification, and prevention therapy. The future needs to include a focus on increased awareness of MOH for the general population and primary prevention strategies for patients and providers.  To achieve success in treatment, it is essential that the primary care provider, nurse practitioner, pharmacist, and internist openly communicate with the neurologist when MOH is suspected.

Interested in Participating?

We are looking for contributors to author, edit, and peer review our vast library of review articles and multiple choice questions. In as little as 2-3 hours you can make a significant contribution to your specialty. In return for a small amount of your time, you will receive free access to all content and you will be published as an author or editor in eBooks, apps, online CME/CE activities, and an online Learning Management System for students, teachers, and program directors that allows access to review materials in over 500 specialties.

Improve Content - Become an Author or Editor

This is an academic project designed to provide inexpensive peer-reviewed Apps, eBooks, and very soon an online CME/CE system to help students identify weaknesses and improve knowledge. We would like you to consider being an author or editor. Please click here to learn more. Thank you for you for your interest, the StatPearls Publishing Editorial Team.

Medication-overuse Headache (MOH) - Questions

Take a quiz of the questions on this article.

Take Quiz
Which of the following is a correct statement regarding medication-overuse headaches?

Click Your Answer Below

Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.

Sign Up
An analgesic rebound headache is defined as the return of a headache within what time period?

Click Your Answer Below

Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.

Sign Up
A 33-year-old female returns to the doctor stating that after taking the prescribed drug, ergotamine tartrate, for the migraines, her headaches have become more frequent and painful. What is the most likely problem?

Click Your Answer Below

Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.

Sign Up

Medication-overuse Headache (MOH) - References


Vandenbussche N,Laterza D,Lisicki M,Lloyd J,Lupi C,Tischler H,Toom K,Vandervorst F,Quintana S,Paemeleire K,Katsarava Z, Medication-overuse headache: a widely recognized entity amidst ongoing debate. The journal of headache and pain. 2018 Jul 13;     [PubMed]
Mathew NT,Reuveni U,Perez F, Transformed or evolutive migraine. Headache. 1987 Feb;     [PubMed]
Classification and diagnostic criteria for headache disorders, cranial neuralgias and facial pain. Headache Classification Committee of the International Headache Society. Cephalalgia : an international journal of headache. 1988;     [PubMed]
The International Classification of Headache Disorders: 2nd edition. Cephalalgia : an international journal of headache. 2004;     [PubMed]
Headache Classification Committee of the International Headache Society (IHS) The International Classification of Headache Disorders, 3rd edition. Cephalalgia : an international journal of headache. 2018 Jan;     [PubMed]
Da Silva AN,Lake AE 3rd, Clinical aspects of medication overuse headaches. Headache. 2014 Jan;     [PubMed]
Wilkinson SM,Becker WJ,Heine JA, Opiate use to control bowel motility may induce chronic daily headache in patients with migraine. Headache. 2001 Mar;     [PubMed]
Shahbeigi S,Fereshtehnejad SM,Mohammadi N,Golmakani MM,Tadayyon S,Jalilzadeh G,Pakdaman H, Epidemiology of headaches in Tehran urban area: a population-based cross-sectional study in district 8, year 2010. Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology. 2013 Jul;     [PubMed]
Global, regional, and national comparative risk assessment of 84 behavioural, environmental and occupational, and metabolic risks or clusters of risks, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet (London, England). 2017 Sep 16;     [PubMed]
Hagen K,Linde M,Steiner TJ,Stovner LJ,Zwart JA, Risk factors for medication-overuse headache: an 11-year follow-up study. The Nord-Trøndelag Health Studies. Pain. 2012 Jan;     [PubMed]
Bigal ME,Serrano D,Buse D,Scher A,Stewart WF,Lipton RB, Acute migraine medications and evolution from episodic to chronic migraine: a longitudinal population-based study. Headache. 2008 Sep;     [PubMed]
Radat F,Lanteri-Minet M, What is the role of dependence-related behavior in medication-overuse headache? Headache. 2010 Nov;     [PubMed]
Shand B,Goicochea MT,Valenzuela R,Fadic R,Jensen R,Tassorelli C,Nappi G, Clinical and Demographical Characteristics of Patients with Medication Overuse Headache in Argentina and Chile: Analysis of the Latin American Section of COMOESTAS Project. The journal of headache and pain. 2015;     [PubMed]
Cevoli S,Sancisi E,Grimaldi D,Pierangeli G,Zanigni S,Nicodemo M,Cortelli P,Montagna P, Family history for chronic headache and drug overuse as a risk factor for headache chronification. Headache. 2009 Mar;     [PubMed]
Sarchielli P,Corbelli I,Messina P,Cupini LM,Bernardi G,Bono G,Di Piero V,Petolicchio B,Livrea P,Prudenzano MP,Pini LA,Sandrini G,Allena M,Tedeschi G,Russo A,Caproni S,Beghi E,Calabresi P, Psychopathological comorbidities in medication-overuse headache: a multicentre clinical study. European journal of neurology. 2016 Jan;     [PubMed]
Bendtsen L,Munksgaard S,Tassorelli C,Nappi G,Katsarava Z,Lainez M,Leston J,Fadic R,Spadafora S,Stoppini A,Jensen R, Disability, anxiety and depression associated with medication-overuse headache can be considerably reduced by detoxification and prophylactic treatment. Results from a multicentre, multinational study (COMOESTAS project). Cephalalgia : an international journal of headache. 2014 May;     [PubMed]
Woolf CJ, Central sensitization: implications for the diagnosis and treatment of pain. Pain. 2011 Mar;     [PubMed]
Schwedt TJ,Chong CD, Medication Overuse Headache: Pathophysiological Insights from Structural and Functional Brain MRI Research. Headache. 2017 Jul;     [PubMed]
Lai TH,Wang SJ, Neuroimaging Findings in Patients with Medication Overuse Headache. Current pain and headache reports. 2018 Jan 16;     [PubMed]
Srikiatkhachorn A,Tarasub N,Govitrapong P, Effect of chronic analgesic exposure on the central serotonin system: a possible mechanism of analgesic abuse headache. Headache. 2000 May;     [PubMed]
Di Lorenzo C,Coppola G,Currà A,Grieco G,Santorelli FM,Lepre C,Porretta E,Pascale E,Pierelli F, Cortical response to somatosensory stimulation in medication overuse headache patients is influenced by angiotensin converting enzyme (ACE) I/D genetic polymorphism. Cephalalgia : an international journal of headache. 2012 Dec;     [PubMed]
Binder DK,Scharfman HE, Brain-derived neurotrophic factor. Growth factors (Chur, Switzerland). 2004 Sep;     [PubMed]
Andersen S,Skorpen F, Variation in the COMT gene: implications for pain perception and pain treatment. Pharmacogenomics. 2009 Apr;     [PubMed]
Serretti A,Calati R,Mandelli L,De Ronchi D, Serotonin transporter gene variants and behavior: a comprehensive review. Current drug targets. 2006 Dec;     [PubMed]
De Felice M,Ossipov MH,Wang R,Lai J,Chichorro J,Meng I,Dodick DW,Vanderah TW,Dussor G,Porreca F, Triptan-induced latent sensitization: a possible basis for medication overuse headache. Annals of neurology. 2010 Mar;     [PubMed]
Coppola G,Currà A,Di Lorenzo C,Parisi V,Gorini M,Sava SL,Schoenen J,Pierelli F, Abnormal cortical responses to somatosensory stimulation in medication-overuse headache. BMC neurology. 2010 Dec 30;     [PubMed]
Boes CJ,Capobianco DJ, Chronic migraine and medication-overuse headache through the ages. Cephalalgia : an international journal of headache. 2005 May;     [PubMed]
Rapoport AM, Medication overuse headache: awareness, detection and treatment. CNS drugs. 2008;     [PubMed]
Tepper D, Medication Overuse Headache. Headache. 2017 May;     [PubMed]
Kristoffersen ES,Straand J,Vetvik KG,Benth JŠ,Russell MB,Lundqvist C, Brief intervention for medication-overuse headache in primary care. The BIMOH study: a double-blind pragmatic cluster randomised parallel controlled trial. Journal of neurology, neurosurgery, and psychiatry. 2015 May;     [PubMed]
Saper JR,Lake AE 3rd, Medication overuse headache: type I and type II. Cephalalgia : an international journal of headache. 2006 Oct;     [PubMed]
Evers S,Jensen R, Treatment of medication overuse headache--guideline of the EFNS headache panel. European journal of neurology. 2011 Sep;     [PubMed]
Zeeberg P,Olesen J,Jensen R, Discontinuation of medication overuse in headache patients: recovery of therapeutic responsiveness. Cephalalgia : an international journal of headache. 2006 Oct;     [PubMed]
Bøe MG,Salvesen R,Mygland A, Chronic daily headache with medication overuse: predictors of outcome 1 year after withdrawal therapy. European journal of neurology. 2009 Jun;     [PubMed]
Pascual J,Berciano J, [Daily chronic headache in patients with migraine induced by abuse of ergotamine-analgesics: response due to a protocol of outpatient treatment]. Neurologia (Barcelona, Spain). 1993 Aug-Sep;     [PubMed]
Saper JR,Da Silva AN, Medication overuse headache: history, features, prevention and management strategies. CNS drugs. 2013 Nov;     [PubMed]
Smith TR, Low-dose tizanidine with nonsteroidal anti-inflammatory drugs for detoxification from analgesic rebound headache. Headache. 2002 Mar;     [PubMed]
Rabe K,Pageler L,Gaul C,Lampl C,Kraya T,Foerderreuther S,Diener HC,Katsarava Z, Prednisone for the treatment of withdrawal headache in patients with medication overuse headache: a randomized, double-blind, placebo-controlled study. Cephalalgia : an international journal of headache. 2013 Feb;     [PubMed]
Bøe MG,Mygland A,Salvesen R, Prednisolone does not reduce withdrawal headache: a randomized, double-blind study. Neurology. 2007 Jul 3;     [PubMed]
Pageler L,Katsarava Z,Diener HC,Limmroth V, Prednisone vs. placebo in withdrawal therapy following medication overuse headache. Cephalalgia : an international journal of headache. 2008 Feb;     [PubMed]
Lu SR,Fuh JL,Juang KD,Wang SJ, Repetitive intravenous prochlorperazine treatment of patients with refractory chronic daily headache. Headache. 2000 Oct;     [PubMed]
Raskin NH, Repetitive intravenous dihydroergotamine as therapy for intractable migraine. Neurology. 1986 Jul;     [PubMed]
Williams DR,Stark RJ, Intravenous lignocaine (lidocaine) infusion for the treatment of chronic daily headache with substantial medication overuse. Cephalalgia : an international journal of headache. 2003 Dec;     [PubMed]
Schwartz TH,Karpitskiy VV,Sohn RS, Intravenous valproate sodium in the treatment of daily headache. Headache. 2002 Jun;     [PubMed]
Trucco M,Meineri P,Ruiz L,Gionco M, Medication overuse headache: withdrawal and prophylactic therapeutic regimen. Headache. 2010 Jun;     [PubMed]
Cheung V,Amoozegar F,Dilli E, Medication overuse headache. Current neurology and neuroscience reports. 2015 Jan;     [PubMed]
Diener HC,Dodick DW,Goadsby PJ,Bigal ME,Bussone G,Silberstein SD,Mathew N,Ascher S,Morein J,Hulihan JF,Biondi DM,Greenberg SJ, Utility of topiramate for the treatment of patients with chronic migraine in the presence or absence of acute medication overuse. Cephalalgia : an international journal of headache. 2009 Oct;     [PubMed]
Russell MB,Lundqvist C, Prevention and management of medication overuse headache. Current opinion in neurology. 2012 Jun;     [PubMed]
Aurora SK,Dodick DW,Turkel CC,DeGryse RE,Silberstein SD,Lipton RB,Diener HC,Brin MF, OnabotulinumtoxinA for treatment of chronic migraine: results from the double-blind, randomized, placebo-controlled phase of the PREEMPT 1 trial. Cephalalgia : an international journal of headache. 2010 Jul;     [PubMed]
Diener HC,Dodick DW,Aurora SK,Turkel CC,DeGryse RE,Lipton RB,Silberstein SD,Brin MF, OnabotulinumtoxinA for treatment of chronic migraine: results from the double-blind, randomized, placebo-controlled phase of the PREEMPT 2 trial. Cephalalgia : an international journal of headache. 2010 Jul;     [PubMed]
Silberstein SD,Blumenfeld AM,Cady RK,Turner IM,Lipton RB,Diener HC,Aurora SK,Sirimanne M,DeGryse RE,Turkel CC,Dodick DW, OnabotulinumtoxinA for treatment of chronic migraine: PREEMPT 24-week pooled subgroup analysis of patients who had acute headache medication overuse at baseline. Journal of the neurological sciences. 2013 Aug 15;     [PubMed]
Tassorelli C,Jensen R,Allena M,De Icco R,Sances G,Katsarava Z,Lainez M,Leston J,Fadic R,Spadafora S,Pagani M,Nappi G, A consensus protocol for the management of medication-overuse headache: Evaluation in a multicentric, multinational study. Cephalalgia : an international journal of headache. 2014 Aug;     [PubMed]
Lai JT,Dereix JD,Ganepola RP,Nightingale PG,Markey KA,Aveyard PN,Sinclair AJ, Should we educate about the risks of medication overuse headache? The journal of headache and pain. 2014 Feb 13;     [PubMed]
Probyn K,Bowers H,Caldwell F,Mistry D,Underwood M,Matharu M,Pincus T, Prognostic factors for chronic headache: A systematic review. Neurology. 2017 Jul 18;     [PubMed]
Hagen K,Jensen R,Bøe MG,Stovner LJ, Medication overuse headache: a critical review of end points in recent follow-up studies. The journal of headache and pain. 2010 Oct;     [PubMed]
Bøe MG,Thortveit E,Vatne A,Mygland Å, Chronic headache with medication overuse: Long-term prognosis after withdrawal therapy. Cephalalgia : an international journal of headache. 2017 Nov;     [PubMed]
Zidverc-Trajkovic JJ,Pekmezovic T,Jovanovic Z,Pavlovic A,Mijajlovic M,Radojicic A,Sternic N, Long-term predictors of remission in patients treated for medication-overuse headache at a specialized headache center: A prospective cohort study. Cephalalgia : an international journal of headache. 2018 Feb;     [PubMed]
Katsarava Z,Muessig M,Dzagnidze A,Fritsche G,Diener HC,Limmroth V, Medication overuse headache: rates and predictors for relapse in a 4-year prospective study. Cephalalgia : an international journal of headache. 2005 Jan;     [PubMed]
Pini LA,Cicero AF,Sandrini M, Long-term follow-up of patients treated for chronic headache with analgesic overuse. Cephalalgia : an international journal of headache. 2001 Nov;     [PubMed]
Tfelt-Hansen P,Krabbe A, Ergotamine abuse. Do patients benefit from withdrawal? Cephalalgia : an international journal of headache. 1981 Mar;     [PubMed]
Sances G,Ghiotto N,Galli F,Guaschino E,Rezzani C,Guidetti V,Nappi G, Risk factors in medication-overuse headache: a 1-year follow-up study (care II protocol). Cephalalgia : an international journal of headache. 2010 Mar;     [PubMed]
Suhr B,Evers S,Bauer B,Gralow I,Grotemeyer KH,Husstedt IW, Drug-induced headache: long-term results of stationary versus ambulatory withdrawal therapy. Cephalalgia : an international journal of headache. 1999 Jan;     [PubMed]
Grazzi L,Andrasik F,D'Amico D,Leone M,Usai S,Kass SJ,Bussone G, Behavioral and pharmacologic treatment of transformed migraine with analgesic overuse: outcome at 3 years. Headache. 2002 Jun;     [PubMed]
The International Classification of Headache Disorders, 3rd edition (beta version). Cephalalgia : an international journal of headache. 2013 Jul;     [PubMed]
Scher AI,Lipton RB,Stewart WF,Bigal M, Patterns of medication use by chronic and episodic headache sufferers in the general population: results from the frequent headache epidemiology study. Cephalalgia : an international journal of headache. 2010 Mar;     [PubMed]
He Z,Dong L,Zhang Y,Kong Q,Tan G,Zhou J, Metabolic syndrome in female migraine patients is associated with medication overuse headache: a clinic-based study in China. European journal of neurology. 2015 Aug;     [PubMed]


The intent of StatPearls is to provide practice questions and explanations to assist you in identifying and resolving knowledge deficits. These questions and explanations are not intended to be a source of the knowledge base of all of medicine, nor is it intended to be a board or certification review of NP-Gerontology Primary Care. The authors or editors do not warrant the information is complete or accurate. The reader is encouraged to verify each answer and explanation in several references. All drug indications and dosages should be verified before administration.

StatPearls offers the most comprehensive database of free multiple-choice questions with explanations and short review chapters ever developed. This system helps physicians, medical students, dentists, nurses, pharmacists, and allied health professionals identify education deficits and learn new concepts. StatPearls is not a board or certification review system for NP-Gerontology Primary Care, it is a learning system that you can use to help improve your knowledge base of medicine for life-long learning. StatPearls will help you identify your weaknesses so that when you are ready to study for a board or certification exam in NP-Gerontology Primary Care, you will already be prepared.

Our content is updated continuously through a multi-step peer review process that will help you be prepared and review for a thorough knowledge of NP-Gerontology Primary Care. When it is time for the NP-Gerontology Primary Care board and certification exam, you will already be ready. Besides online study quizzes, we also publish our peer-reviewed content in eBooks and mobile Apps. We also offer inexpensive CME/CE, so our content can be used to attain education credits while you study NP-Gerontology Primary Care.