Changes

April to May 2022 — reviewed. A literature search was conducted in April 2022 to identify evidence-based guidelines, UK policy, systematic reviews, and key randomized controlled trials published since the last revision of the topic. The recommendations have been updated in line with current evidence in the literature. No major changes to the recommendations have been made.

Update

Goals

To support primary healthcare professionals to:

• Recognize headache due to medication overuse.
• Assess whether a person is suitable for drug withdrawal in primary care and provide appropriate support.
• Arrange specialist referral for drug withdrawal if appropriate.
• Give advice on prevention of medication overuse headache.

Outcome measures

No outcome measures were found during the review of this topic.

Audit criteria

No audit criteria were found during the review of this topic.

QOF indicators

No QOF indicators were found during the review of this topic.

QIPP - Options for local implementation

No QIPP indicators were found during the review of this topic.

NICE quality standards

The following NICE quality standard is relevant for this CKS topic:

• Statement 2. People with a primary headache disorder are given information on the risk of medication overuse headache.

[NICE, 2013]

What is it?

• The International Classification of Headache Disorders (ICHD) categorizes headache into [IHS, 2018] [Ahmed, 2019]:
  • Primary headaches — these are not associated with another underlying condition, and include migraine, tension-type headache, and cluster headache. See the CKS topics on Migraine, Headache - tension-type, and Headache - cluster for more information.
  • Secondary headaches — these are precipitated by another condition or disorder (local or systemic) and include headache attributed to use of or exposure to a substance, including medication overuse headache.
    • See the CKS topic on Headache - assessment for more examples of primary and secondary headache disorders.
• The ICHD defines medication overuse headache as [IHS, 2018]:
  • Headache occurring on 15 or more days per month in a person with a pre-existing primary headache disorder, which develops as a consequence of regular overuse of one or more drugs that can be taken for acute and/or symptomatic treatment of headache, for more than 3 months. It usually, but not always, resolves after the overused medication is stopped.
    
    • Ergotamines, triptans, opioids, or combination analgesics are taken on 10 days or more per month [Ahmed, 2019; Steiner, 2019; NICE, 2021].
    • Simple analgesics such as paracetamol, nonsteroidal anti-inflammatory drugs (NSAIDs), or aspirin (either alone or in any combination) are taken on 15 days or more per month [Ahmed, 2019; Steiner, 2019; NICE, 2021].
  • The headache is not better accounted for by another ICHD-3 diagnosis.
• Medication overuse headache is a chronic headache disorder, and the pre-existing primary headache is migraine in 60–80% of people, or more rarely tension-type headache [Alstadhaug, 2017] [Ahmed, 2019] [Diener, 2020].
  • Medication overuse headache is generally of the same phenotype as the primary headache [Ahmed, 2019; Diener, 2020]. Very rarely, there may be an underlying secondary headache disorder [Diener, 2020].
  • Most people with medication overuse headache overuse more than one drug [Da Silva, 2014; Diener, 2020].
  • The condition was previously referred to as 'rebound headache', 'drug-induced headache', or 'medication-misuse headache' [Da Silva, 2014].

What causes it?

The exact pathophysiological mechanism responsible for medication overuse headache is not yet known, but it is thought to be a complex interaction between medication overuse and individual susceptibility [Alstadhaug, 2017] [Ahmed, 2019]. Proposed risk factors include:

• Primary headache disorder — a pre-existing primary headache diagnosis of migraine or tension-type headache (or both), or more rarely other primary headaches such as cluster headache [Alstadhaug, 2017; Ahmed, 2019; Diener, 2020].
  • High headache frequency at baseline increases the risk.
  • Interestingly, medication overuse headache rarely develops in people without a history of headache when analgesics are taken regularly for another condition, such as inflammatory bowel disease or joint pain.
• Pain medication — frequent use of pain medication increases the risk [Da Silva, 2014; Alstadhaug, 2017; Diener, 2020].
  • Overuse of triptans has been shown to cause medication overuse headache faster and at lower dosages compared with simple analgesics. A prospective study of 98 people with medication overuse headache who underwent standardized inpatient medication withdrawal found the average interval between the first intake and daily medication overuse headache was 1.7 years for triptans, 2.7 years for ergotamines, and 4.8 years for simple analgesics [Limmroth, 2002].
• Psychosocial — psychological comorbidities (such as anxiety and depression), other chronic pain conditions, and/or dependence-related behaviours including use of tranquilizers [Alstadhaug, 2017; Ahmed, 2019; Diener, 2019; Diener, 2020].
• Genetics — the risk appears to be greater in females and in people with a family history of medication overuse headache or other substance misuse [Kristoffersen, 2014; Diener, 2020].
  • Polymorphism in several genes has been postulated as a contributing factor in some people [Alstadhaug, 2017].
• Neurological — acquired central sensitization may have a role in the cause of chronic headache, and appears to normalize after withdrawal of overused medications [Diener, 2020].
  • Changes in central pain networks, neuronal hyperexcitability, and sensitization of both peripheral and central nociceptive pathways may be involved [Alstadhaug, 2017].

How common is it?

Prevalence estimates of medication overuse headache vary depending on the study setting, study sample, methodology, and definitions used [Diener, 2019].

• The 1-year prevalence of medication overuse headache is estimated to be 1–2% of the general population worldwide [Ahmed, 2019].
  • It affects up to 20–50% of people with chronic headache [Ahmed, 2019]. The European Academy of Neurology guideline states that in people with chronic headache, particularly chronic migraine, the prevalence is as high as 70% [Diener, 2020].
  • It is more prevalent in females than males with an estimated male to female ratio of 1:3–4 cited in a review of European epidemiological studies [Kristoffersen, 2014].
  • The prevalence is highest in people aged 40–49 years [Kristoffersen, 2014].
  • The prevalence appears to decrease with increasing age [Alstadhaug, 2017].

What are the complications?

Complications of medication overuse headache may include:

• Stress, anxiety, and depression [Da Silva, 2014; Ahmed, 2019]. See the CKS topics on Depression and Generalized anxiety disorder for more information.
• Insomnia and sleep disturbance [Da Silva, 2014]. See the CKS topic on Insomnia for more information.
• Reduced quality of life and a negative impact on home, work, and social life associated with chronic headache [Kristoffersen, 2014; Steiner, 2019].
• If untreated, an increased risk of transition from episodic to chronic migraine [Ahmed, 2019; Diener, 2019]. See the CKS topic on Migraine for more information.

What is the prognosis?

Most people with medication overuse headache improve after withdrawal of overused medication [Diener, 2020]. The responsiveness of the underlying primary headache disorder to preventative drug treatment also improves [Ahmed, 2019].

• Following successful drug withdrawal, most cases revert to an episodic primary headache disorder, such as migraine or tension-type headache. The prognosis depends on [Steiner, 2019; Diener, 2020]:
  • The initial type of primary headache disorder — more frequent relapses with migraine combined with tension-type headache, compared with migraine alone.
  • The class of medication overused — opioids have a worse prognosis compared with triptans.
  • The duration of drug overuse — worse prognosis with longer use.
  • Other comorbidities, such as psychological disorders and/or other causes of chronic pain.
  • Timescale since drug withdrawal — the relapse rate is high within the first year after drug withdrawal.
• The British Association for the Study of Headache (BASH) guideline states that 22–45% of affected people relapse within 1 year, and 40–60% within 4 years of withdrawing from overused medications [Ahmed, 2019].
• In a multicentre, multinational consensus group interventional study of people with medication overuse headache for 5–10 years before drug withdrawal (n = 376) who were followed up for 6 months [Tassorelli, 2014]:
  • In 72.9% of participants who completed drug withdrawal, medication overuse headache had resolved.
  • In 46.5% of participants, headache had reverted to episodic migraine or tension-type headache.
• A Norwegian prospective cohort study of adults with chronic headache and medication overuse for 5–10 years (n = 109) who were given brief advice and followed up after 18 months found [Grande, 2011]:
  • 76% of participants no longer had medication overuse.
  • 42% of participants no longer had a chronic headache.
• In a prospective Danish study of 175 people with probable medication overuse headache (with a combination of migraine and tension-type primary headache) followed up at 8 weeks post drug withdrawal [Zeeberg, 2006]:
  • In 45% of participants there was an improvement in headache of at least 50%.
  • In 48% of participants there was no change in headache frequency.
  • In 7% of participants there was an increase in headache frequency.

When should I suspect medication overuse headache?

The phenotype of medication overuse headache usually depends on the underlying primary headache disorder and the type of medication being overused.

• The International Classification of Headache Disorders (ICHD) defines medication overuse headache as:
  • Headache occurring on 15 or more days per month in a person with a pre-existing primary headache disorder, which develops as a consequence of regular overuse of one or more drugs that can be taken for acute and/or symptomatic treatment of headache, for more than 3 months. It usually, but not always, resolves after the overused medication is stopped.
    
    • Ergotamines, triptans, opioids, or combination analgesics are taken on 10 days or more per month.
    • Simple analgesics such as paracetamol, nonsteroidal anti-inflammatory drugs (NSAIDs), or aspirin (either alone or in any combination) are taken on 15 days or more per month.
  • The headache is not better accounted for by another ICHD-3 diagnosis.
• Note: the use of a headache diary to assess headache symptoms and correlate with acute medication use may be helpful to clarify the diagnosis. Headache may vary in site, intensity, and character, and may be worse early in the morning. There may be a history of increasingly frequent and difficult-to-treat headache episodes with increasing medication use. See the CKS topic on Headache - assessment for more information.
• Note: triptan overuse may result in daily migraine-like headache or an increase in migraine frequency, whereas overuse of other analgesics may lead to daily headache with features of both migraine and tension-type headache. See the CKS topics on Migraine and Headache - tension-type for more information.

What else might it be?

Headache is a common symptom which can be associated with many conditions. Medication overuse headache may exacerbate or co-exist with other headache disorders such as migraine and tension-type headache, as well as other more rare or serious conditions.

• Primary headache disorders:
  • Chronic migraine. See the CKS topic on Migraine for more information.
  • Chronic tension-type headache. See the CKS topic on Headache - tension-type for more information.
  • Trigeminal autonomic cephalalgias, such as cluster headache, paroxysmal hemicrania, and hemicrania continua. See the CKS topic on Headache - cluster for more information.
  • Other — primary cough or exercise headache and cold-stimulus headache.
• Other secondary headache disorders:
  • Trauma or injury to the head and/or neck. See the CKS topics on Neck pain - acute torticollis, Neck pain - cervical radiculopathy, and Neck pain - non-specific for more information.
  • Cranial or cervical vascular disorders such as intracerebral haemorrhage, central venous thrombosis, or temporal arteritis. See the CKS topics on Stroke and TIA and Giant cell arteritis for more information.
  • Non-vascular intracranial disorders such as idiopathic intracranial hypertension or brain malignancy. See the CKS topics on Brain and central nervous system cancers - recognition and referral and Head and neck cancers - recognition and referral for more information.
  • Exposure to a substance (such as carbon monoxide, alcohol, cocaine); substance withdrawal (such as caffeine, opioids, or oestrogen). See the CKS topics on Carbon monoxide poisoning, Alcohol - problem drinking, and Opioid dependence for more information.
  • Infection (may be intracranial infection such as bacterial or viral meningitis, encephalitis, or cerebral abscess) or systemic infection. See the CKS topic on Meningitis - bacterial meningitis and meningococcal disease for more information.
  • Disorders of homeostasis such as hypoxia or hypertension including pregnancy-induced hypertension and eclampsia. See the CKS topics on Hypertension and Hypertension in pregnancy for more information. 
  • Disorders of the cranium, neck, eyes, ears, nose, sinuses, teeth, mouth, or other facial or cranial structure such as acute angle-closure glaucoma, temporomandibular disorders, dental problems, otitis media, or sinusitis. See the CKS topics on Glaucoma, Otitis media - acute, Otitis media with effusion, Sinusitis, and Temporomandibular disorders (TMDs) for more information.
  • Psychiatric disorders such as somatization disorder or psychotic disorder. See the CKS topic on Psychosis and schizophrenia for more information.
• Painful cranial neuropathies, other facial pains, and other headaches — includes conditions such as post-herpetic neuralgia, trigeminal neuralgia, and optic neuritis. See the CKS topics on Post-herpetic neuralgia and Trigeminal neuralgia for more information.

Scenario: Management of medication overuse headache

From age 16 years onwards.

Search strategy

Scope of search

A literature search was conducted for guidelines, systematic reviews and randomized controlled trials on primary care management of headache caused by overuse of medication.

Search dates

August 2017 - April 2022

Key search terms

Various combinations of searches were carried out. The terms listed below are the core search terms that were used for Medline.

• exp Headache/, exp Headache Disorders, Secondary/, medication overuse headache.tw, rebound headache.tw, drug induced headache.tw, medication misuse headache.tw,
• Headache / chemically induced*
• (headache$ medication overuse) or (medication overuse headache$) or MOH.ti,ab.

Sources of guidelines

• National Institute for Health and Care Excellence (NICE)
• Scottish Intercollegiate Guidelines Network (SIGN)
• Royal College of Physicians
• Royal College of General Practitioners
• Royal College of Nursing
• NICE Evidence
• World Health Organization
• Guidelines International Network
• TRIP database
• Agency for Healthcare Research and Quality
• Institute for Clinical Systems Improvement
• National Health and Medical Research Council (Australia)
• Royal Australian College of General Practitioners
• British Columbia Medical Association
• Canadian Medical Association
• Alberta Medical Association
• Michigan Quality Improvement Consortium
• Singapore Ministry of Health
• National Resource for Infection Control
• RefHELP NHS Lothian Referral Guidelines
• Medline (with guideline filter)
• Driver and Vehicle Licensing Agency
• NHS Health at Work (occupational health practice)

Sources of systematic reviews and meta-analyses

• The Cochrane Library:
  • Systematic reviews
  • Protocols
  • Database of Abstracts of Reviews of Effects
• Medline (with systematic review filter)
• EMBASE (with systematic review filter)

Sources of health technology assessments and economic appraisals

• NIHR Health Technology Assessment programme
• The Cochrane Library:
  • NHS Economic Evaluations
  • Health Technology Assessments
• Canadian Agency for Drugs and Technologies in Health
• International Network of Agencies for Health Technology Assessment

Sources of randomized controlled trials

• The Cochrane Library:
  • Central Register of Controlled Trials
• Medline (with randomized controlled trial filter)
• EMBASE (with randomized controlled trial filter)

Sources of evidence based reviews and evidence summaries

• Bandolier
• Drug and Therapeutics Bulletin
• TRIP database
• Central Services Agency COMPASS Therapeutic Notes

Sources of national policy

• Department of Health
• Health Management Information Consortium (HMIC)

Patient experiences

• Healthtalk
• BMJ - Patient Journeys

Sources of medicines information

The following sources are used by CKS pharmacists and are not necessarily searched by CKS information specialists for all topics. Some of these resources are not freely available and require subscriptions to access content.

• British National Formulary (BNF)
• electronic Medicines Compendium (eMC)
• European Medicines Agency (EMEA)
• LactMed
• Medicines and Healthcare products Regulatory Agency (MHRA)
• REPROTOX
• Scottish Medicines Consortium
• Stockley's Drug Interactions
• TERIS
• TOXBASE
• Micromedex
• UK Medicines Information

Stakeholder engagement

Our policy

The external review process is an essential part of CKS topic development. Consultation with a wide range of stakeholders provides quality assurance of the topic in terms of:

• Clinical accuracy.
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Evidence exclusion criteria

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Studies identified during literature searches are reviewed to identify the most appropriate information to author a CKS topic, ensuring any recommendations are based on the best evidence. We use the principles of the GRADE and PICOT approaches to assess the quality of published research. We use the principles of AGREE II to assess the quality of published guidelines.

Standard exclusions for scoping literature:

• Animal studies
• Original research is not written in English

Possible exclusions for reviewed literature:

• Sample size too small or study underpowered
• Bias evident or promotional literature
• Population not relevant
• Intervention/treatment not relevant
• Outcomes not relevant
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• Setting not relevant
• Not relevant to UK
• Incorrect study type
• Review article
• Duplicate reference

Organizational, behavioural and financial barriers

Our policy

The CKS literature searches take into consideration the following concepts, which are discussed at the initial scoping of the topic.

• Feasibility
  • Studies are selected depending on whether the intervention under investigation is available in the NHS and can be practically and safely undertaken in primary care.
• Organizational and Financial Impact Analysis
• Studies are selected and evaluated on whether the intervention under investigations may have an impact on local clinical service provision or national impact on cost for the NHS. The principles of clinical budget impact analysis are adhered to, evaluated and recorded by the author. The following factors are considered when making this assessment and analysis.
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  • Condition-related costs
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  • Time dependencies
• Cost-effectiveness or cost-benefit analysis studies are identified where available. 

We also evaluate and include evidence from NICE accredited sources which provide economic evaluations of recommendations, such as NICE guidelines. When a recommended action may not be possible because of resource constraints, this is explicitly indicated to healthcare professionals by the wording of the CKS recommendation.

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• Personal financial interests
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Competing interests declared for this topic:

None.