Approach

Key Points

  • Medication overuse headache (MOH) is a chronic secondary headache disorder attributable to overuse of acute medications by a person with a pre-existing primary headache (almost always migraine and/or tension-type headache).​[1][10]

  • Overusing acute headache medications, such as simple analgesics, ergot derivatives, triptans, barbiturates, or opioids, often worsens the headache frequency in patients with underlying headache disorders, leading to a transition from an episodic to a chronic headache that occurs on more days than not.

  • The diagnosis is clinical and requires careful history-taking and examination. Investigations are not required unless there are red flags to suggest an alternative cause for the headache.

  • A headache diary is critical to determine the headache frequency and intensity, and quantify the use of acute medication.

  • MOH is common but is preventable and is often treatable.

MOH is a chronic secondary headache disorder attributable to overuse of acute medications by a person with a pre-existing primary headache, usually migraine or tension-type headache (TTH).​[1][10][30]​​

  • The diagnosis of MOH is clinical and focuses on a careful history, together with an assessment for any red flags and exclusion of other potential causes of a secondary headache.[10][27]

  • Consider the possibility of MOH in any patient with a primary headache disorder who reports that an episodic headache has increased in frequency over time to become chronic (occurring on more days than not) and is associated with frequent use of single or combination acute medication.

Make a diagnosis of MOH if the patient meets all three of the criteria set out in the 2018 International Classification of Headache Disorders (ICHD-3):[1]

  • Headache on ≥15 days per month on a background of a pre-existing primary headache disorder.

  • Regular overuse for >3 months of acute treatments (at any dose) for the pre-existing headache disorder. Overuse is defined by:

    • use of simple analgesics on ≥15 days per month (paracetamol, aspirin, or other non-steroidal anti-inflammatory drug [NSAID], alone or in any combination), or

    • use of a triptan, opioid, or ergot derivative on ≥10 days per month, or

    • use of a combination of analgesics from different classes on ≥10 days per month.

  • No other ICHD-3 headache diagnosis better accounts for the symptoms.

History

Ask about the history of the primary headache disorder, when the headaches started to increase in frequency, and how often they now occur. Be aware that migraine is by far the most common underlying headache.

  • Migraine is the underlying primary headache condition affecting around 80% of adults with MOH.[27][28]​ Up to 90% of patients with MOH have a history of migraine and/or TTH.[2][3][4]​​

  • Adults newly diagnosed with MOH have typically had a diagnosis of the underlying headache disorder for an average of 20 years.[10]​ The peak prevalence of MOH occurs in the 50-60 years age group.[9]

  • The typical history is a background of migraine that has increased in frequency and/or severity over months or years, accompanied by escalating use of acute or symptomatic medication, which leads to a transition from an episodic to a chronic pattern of headache.[5][6]

Ask which acute medications are being used and how often each is being taken. Ensure that this covers both prescription medications and over-the-counter drugs.[30]​ It is important to get specific information on this as the details can have an impact on the most appropriate treatment approach.[27]

  • Common medications associated with MOH are triptans, ergot derivatives, simple analgesics (including aspirin and other NSAIDs, or paracetamol), opioids, barbiturates, or benzodiazepines.

  • A cross-sectional survey of 13,649 US adults with migraine found that medication overuse was more common in those using triptans, opioids, and barbiturates and less likely in those using NSAIDs.[2]

  • Some evidence suggests that MOH develops over a shorter period when triptans, opioids, or combination analgesics are overused compared with simple analgesics.[6][30]​ One study found that the average time period between first use of the acute medication and development of daily MOH was 1.7 years for triptans, 2.7 years for ergot derivatives and 4.8 years for analgesics.[32]

  • Bear in mind that the individual may be overusing >1 medication.[27]​ If the patient is using multiple drug classes for symptomatic treatment of the underlying headache, they can be diagnosed with MOH if acute medication is being used on ≥10 days/month, even if no individual drug class is being overused.[1]

  • Data from clinical trials suggest that frequent use of oral calcitonin gene-related peptide (CGRP) antagonists does not seem to lead to MOH.[10][33]​​​

  • Among children and adolescents with a primary headache disorder, the literature reports overuse of medication in 10% to 60%.[34]​ NSAIDs are the most commonly overused medications, followed by paracetamol and triptans.[35]

Ask the patient whether any pain medication is being used for a different medical condition (e.g., a musculoskeletal disorder).

  • MOH can develop in an individual with an episodic primary headache who is using pain medication for another condition (rather than for the primary headache disorder).[27]

Ask about the characteristics and duration of the headache. These vary widely in MOH and can be affected by the primary underlying headache and the type of medication that is being overused.[27]

  • The patient may develop a new type of headache or experience a worsening frequency of their pre-existing headache.

  • One prospective study found that patients with migraine and/or TTH who overused analgesic medication were more likely to develop a dull, diffuse, holocranial headache without migrainous symptoms. In contrast, those who overused triptans for underlying migraine were more likely to develop a daily migrainous headache (unilateral pulsating headache with autonomic disturbances).[32]

If you suspect MOH based on the history, ask the patient to keep a headache diary or calendar.[10][30]​​​​ This is a key tool to quantify headache frequency and use of acute medication and thereby confirm that the diagnostic thresholds for MOH have been reached.

  • In addition to determining the frequency of headache and tracking use of acute or symptomatic medication, the headache diary can also help to indicate headache features, identify patterns or triggers, and act as a baseline to monitor the effectiveness of treatment.

  • Electronic diaries are available that prompt the patient to complete daily reports. Such diaries often include options for recording the presence of a headache, a scale to rate its severity, and boxes to note specific symptomatic features (e.g., aura, photophobia, vomiting). They also allow the patient to record use of different medication classes used to relieve symptoms.[10] The Migraine Trust: keeping a headache diary Opens in new window British Association for the Study of Headache: headache diary Opens in new window​​

The diagnosis of MOH is made in addition to the diagnosis of the underlying headache disorder.[1]​ A diagnosis of MOH implies that the overused medication is the cause of the frequent headache.[10]

  • However, while the 2004 edition of the ICHD diagnostic criteria required an improvement in the headache after withdrawal of the causative medication, this requirement was removed in 2018 as part of ICHD-3.[1][36]

  • The ICHD-3 criteria state that MOH usually, but not invariably, resolves after withdrawal of the overused acute medication.[1]

  • In clinical practice, this can sometimes make it difficult to distinguish MOH from a scenario in which a rising frequency of headache from the pre-existing headache disorder has led to increasing use of acute medication.[10]

  • Some patients who meet the diagnostic criteria for MOH do not see an improvement after withdrawal of the overused medication, with the proportion varying between studies that used different withdrawal protocols.[27] It is also worth noting that not every individual with an episodic primary headache disorder who overuses acute medication (either for the headache or for another chronic condition) will transition to an increased headache frequency. As such, it can be difficult in practice to distinguish between medication overuse as a cause of MOH and a scenario in which the medication overuse is a consequence rather than a cause of increasingly frequent headaches.[10]

  • Note that medication overuse in general is distinct from MOH because patients without an underlying headache disorder who overuse analgesia for other pain conditions do not develop chronic headache.[27]

Be aware of comorbidities that are commonly associated with MOH as they may contribute to the development or exacerbation of the condition and, in some cases, reduce the likelihood of successful treatment. In practice, however, it can be difficult to distinguish whether such conditions are true risk factors for MOH or simple comorbidities.[10]

  • Depression and anxiety are strong independent risk factors for chronification of the primary headache, which can lead in turn to medication overuse. They are the most frequent comorbidities among patients with MOH and are predictors of a worse outcome from treatment.[9][17][18]​​​[19][30]

  • Chronic musculoskeletal disorders have been found to be associated with a twofold increased risk of MOH.[4]​ Note that MOH can develop in a patient with an episodic primary headache who uses pain medication for a condition such as arthritis (rather than for the primary headache disorder).[27]

  • There have also been suggestions that patients with MOH are more likely than the general population to have gastrointestinal problems, insomnia, hypothyroidism, and metabolic syndrome, although the evidence for this is limited.[10]

  • Check for any history of substance misuse disorder. Evidence suggests a possible link in some patients between overuse of medication or the development of MOH and substance misuse disorder. Moreover, emerging findings indicate that individuals with MOH have an increased familial risk of drug dependence and a possible genetic association with dopaminergic and drug-dependence molecular pathways.[10][37][38]​​​​ The Severity of Dependence Scale (SDS) score is a significant predictor of medication overuse among patients with headache disorders.[1]

Female sex is another significant risk factor for MOH.

  • MOH is more common in women than in men. A prospective longitudinal study of 25,596 individuals in Norway with an 11-year follow-up found that female sex was associated with a 1.9-fold increased risk of MOH compared with male sex (95% CI 1.4 to 2.6), and an epidemiological survey of 44,300 randomly selected women in Sweden reported a female-to-male ratio of 2.8:1.[4][16]

  • This reflects the predominance of migraine among females. Evidence suggests that the sex ratio associated with migraine changes from 1:1 in pre-pubertal children to a 2:1 predominance of girls during adolescence.[39]​ Functional MRI (fMRI) studies of pre- and post-pubertal individuals with migraine have found that distinct changes in brain connectivity during puberty are associated with an increased post-pubertal headache burden in females.[40]

One longitudinal study found that a lower level of education and lower household income were also associated with MOH.[4]

​Categorise the patient's MOH as uncomplicated or complicated. This may have implications for the most appropriate management plan.[27]

  • Uncomplicated MOH refers to individuals who overuse simple analgesics, triptans, or ergot derivatives; have no significant psychiatric comorbidity; and have no past history of an MOH relapse.

  • Complicated MOH refers to individuals who overuse opioids, benzodiazepines, barbiturates, or other sedatives, and/or have a significant psychiatric comorbidity and/or have a history of relapse after previous treatment for MOH.

Be aware that MOH has a substantial negative impact on quality of life and daily functioning, with patients experiencing lower scores than the general population on validated measures such as SF-36 and SF-12, including reduced Physical Health Composite Scores (PCS-12) and Mental Health Composite Scores (MCS-12), as observed in both clinical and population-based studies.[15]

  • MOH is a significantly disabling condition, often requiring frequent routine or urgent care consultations. Effective treatment can lead to lower healthcare and wider economic costs in addition to improving quality of life.[18][41][42]

Red flags in the history

Check for any red flags in the history that should raise suspicion of an alternative cause of secondary headache. These include some elements of the SNOOP4 or SNNOOP10 mnemonics for red flag symptoms and signs in a patient who presents with headache.[43][44]​​​​ The red flags that are most relevant in the context of a patient suspected of having MOH are:[43][44]

  • Abnormal neurological symptoms: could be suggestive of a variety of conditions that need to be ruled out, such as brain tumour, brain abscess, spontaneous intracranial hypotension, cerebral venous sinus thrombosis.

  • Headache aggravated by postural changes or Valsalva manoeuvre: may be a feature of intracranial hypertension or hypotension.

  • Systemic symptoms or features, such as fever or weight loss: fever could indicate a secondary headache attributable to infection, particularly if the patient has a history of HIV or other immunosuppression. Weight loss might be a symptom of malignancy.

  • A history of cancer: potential for brain metastasis.

  • Older age (>50 years): consider the possibility of giant cell arteritis.[30]

  • History of trauma: may indicate the possibility of a persistent headache attributable to traumatic brain injury.

  • Pregnancy or puerperium: exclude pre-eclampsia, cerebral sinus thrombosis, hypothyroidism, anaemia, gestational diabetes.

Physical examination

​The diagnostic criteria for MOH do not include any physical signs, and there are usually no findings of note on examination.[1]

  • An unremarkable neurological examination is an important prerequisite for diagnosing MOH.[10]

  • Any motor weakness or sensory deficit should prompt suspicion for a brain tumour.[43]

​Focus the physical examination on excluding red flags and identifying any other potential signs of an alternative cause for secondary headache.[30]​ Serious causes of secondary headache are very uncommon.[30] Among the most concerning signs to look for (and the potential underlying conditions that need to be ruled out if present) are:[43]

  • Papilloedema on ophthalmological examination (idiopathic intracranial hypertension [also known as pseudotumor cerebri] or brain tumour)[30]

  • Visual field defect (pituitary tumour)

  • Neck tenderness with limited range of motion (cervical myofascial pain syndrome)

  • Localised pain, induration, tenderness, or erythematous nodules over or along both temporal arteries (giant cell arteritis, especially if >50 years of age)

  • Jaw tenderness (temporomandibular joint disorder)

  • Joint hypermobility (cerebral spinal fluid leak)

  • Cranial nerve palsy (chronic meningitis)

  • Orthostatic tachycardia (postural orthostatic tachycardia syndrome)

Initial investigations

The diagnosis of MOH is clinical, based on the ICHD-3 criteria.[1]​ No specific biomarkers, blood tests, or neuroimaging studies are available to confirm the diagnosis. Such tests are only indicated if there are red flags or other symptoms or signs that indicate the need to rule out an alternative diagnosis.[45]

Other investigations

If there are any red flags or other symptoms or signs in the history or physical examination that suggest an alternative diagnosis, consider ordering further investigations. These may include neuroimaging, blood tests, lumbar puncture, and cerebrospinal fluid (CSF) studies.[10][43]

Magnetic resonance imaging (MRI) (either without contrast, or both without and with contrast) is the recommended investigation for most adult patients who have one or more red flags and is recommended for any child with a secondary headache.[45] Computed tomography (CT) without contrast may be appropriate if intracranial hypertension is suspected, or there are neurological deficits or a history of cancer or immunosuppression.[45] 

Blood tests may reveal signs of infection or giant cell arteritis (elevated erythrocyte sedimentation rate). Lumbar puncture may be indicated if there is suspicion of meningitis or encephalitis and can also be used to measure cerebrospinal fluid pressure in patients with papilloedema.

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