Treatment algorithm

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer

ACUTE

adults: uncomplicated

1st line – withdrawal from/reduction of acute medication ± rescue medication

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ACUTE
|
adults: uncomplicated
1st line – 

withdrawal from/reduction of acute medication ± rescue medication

Withdrawal of the causative medication(s), or severely restricting its use, is an important element in management of MOH and can lead many patients to revert from chronic to episodic headache.[27][30]​​​

  • Advise the patient that aiming for complete withdrawal is often more effective than limited ongoing use of the overused medication(s).[61][62]

Patient education is an essential first step in managing medication overuse, and may be sufficient on its own to bring about reduction in use of the acute medication and resolution of the MOH in some patients.[1][27][30]

  • Advice on its own is an appropriate initial treatment approach in patients with uncomplicated MOH (i.e., they overuse triptans, simple analgesics, or ergot derivatives; do not have a major psychiatric comorbidity; and have not relapsed after previous successful treatment for MOH).[27] The advice can be provided by a primary care physician, trained headache nurse, or neurologist.[27]

  • When providing education, ensure that the patient understands the concept of MOH and how the frequent use of acute medications can lead to more frequent headaches that become chronic over time.​[6][10]​​

  • Evidence from randomised trials suggests that a primary care-based education intervention can be highly effective for uncomplicated MOH.[58][59][60]

  • Ensure that the patient is forewarned that the headache may worsen when the acute medication is reduced or terminated, but reassure them that this is transient.[10][57]

Patients with uncomplicated MOH can be successfully managed by primary care physicians.[27]

  • Withdrawal of triptans, ergot derivatives, and simple analgesics can be undertaken in outpatient settings.[10]

  • Abrupt discontinuation is probably safe and effective for ergot derivatives, triptans, or simple analgesics (including paracetamol, aspirin, and other non-steroidal anti-inflammatory drugs [NSAIDs]).[27] In practice, any need for tapering is decided based on the patient's individual characteristics.

  • After medication withdrawal, the improvement in headache frequency may be gradual and can take up to 12 weeks.[30]

Ensure that the patient is prepared for a transient worsening of symptoms prior to the start of withdrawal.[64]

  • Withdrawal symptoms can last for 2-10 days (average 3.5 days) and can include withdrawal headache, nausea, vomiting, arterial hypotension, tachycardia, sleep disturbance, anorexia, and anxiety.[27][30]

  • In practice, it is important to encourage the patient to identify the most suitable time to attempt withdrawal (e.g., during a period of leave from work) and to pre-warn their family and friends.

Provide an alternative acute medication (with limited frequency of use) for breakthrough headaches that occur during withdrawal.

  • Symptomatic treatment ('rescue' or 'bridging' medication) is often required to mitigate the symptoms of breakthrough headache that occur when the overused medication is withdrawn.​[9][10]​​ There is no trial evidence to guide selection of bridging medication; hence, recommendations are based on expert consensus.[6]

  • For breakthrough headache, select a medication from a different drug class from the overused medication (e.g., an analgesic if triptans are overused, and vice versa).[10][27]

  • Other options for bridging therapy during withdrawal are medications recommended for acute migraine (e.g., prochlorperazine or metoclopramide, diphenhydramine, and valproate). Note that valproate must not be used in pregnancy or in women of childbearing potential unless they are following a pregnancy prevention programme and specific conditions are met.[27] Systemic corticosteroids are sometimes used for more severe withdrawal symptoms, although the evidence to support this is not strong.[10][27] For more information on rescue therapy options in pregnant and non-pregnant adults, see Migraine headache in adults or Tension-type headache.

Advise the patient to stay off the withdrawn medication for at least 2 weeks and ideally 1 month.[6]​ In the UK, the National Institute for Health and Care Excellence (NICE) recommends at least 1 month.[57]

  • Once the MOH has been successfully treated, the previously overused medication can be reintroduced, but ensure a reduced frequency of use to avoid relapse.

Note that various strategies for managing MOH are used in practice. These include discontinuation of the overused medication without use of preventative medication; discontinuation supported by concurrent preventative medication; or initiation of preventative medication together with restricted frequency of the acute overused medication.[10][27]​ Studies have produced varying conclusions; hence, there is limited evidence to support the benefits of one approach over another.[10] One review co-authored by US and European experts has recommended a combination of education, discontinuation of the overused medication, and early use of preventative medication for any patient with uncomplicated MOH who is willing to attempt withdrawal.[10]

  • Local protocols for MOH are an additional factor that may determine the strategy. In the UK, NICE recommends: advise any patient with MOH to abruptly stop taking all overused acute medications for at least 1 month, and consider preventative treatment alongside this.[57]

Pregnant patients

The same broad principles apply to management of MOH in pregnancy as in any other adult patient, with education, withdrawal of the overused medication, and an effective preventative strategy for the primary headache disorder all important.

Non-pharmacological strategies are preferred wherever possible. If medication is needed either as part of bridging therapy or as the preventative strategy for the underlying headache, the safest available medication at the lowest dose for the shortest duration is recommended.

Note that the American College of Obstetricians and Gynecologists has published specific recommendations for management of headaches in pregnancy and the postnatal period.[101]

For more detail on acute and symptomatic management options in pregnancy, see Migraine headache in adults or Tension-type headache.

Consider – pharmacological preventative therapy

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ACUTE
|
adults: uncomplicated
|
with migraine as underlying disorder
Consider – 

pharmacological preventative therapy

Additional treatment recommended for SOME patients in selected patient group

Preventative medication that targets the underlying headache disorder is an important part of the management plan for many patients with MOH.[10][27]​​​

  • In principle, preventative medication can be used: before withdrawal of the overused medication; from the start of withdrawal as part of a combination strategy; or after withdrawal is complete.[10]

  • In practice, the combination approach is often taken, with initiation of a preventative regimen used to facilitate withdrawal from the overused medication(s).

  • A preventative regimen alone may be the best available option if the patient has uncomplicated MOH and is unwilling to discontinue the overused medication.​[9][10]​​ This has been found to be non-inferior to preventative medication with acute medication withdrawal.[54]

The goal of preventative medication is to target the underlying headache disorder.[10] Use one of the following preventative medication options in patients with migraine as the underlying primary headache disorder:​[6][27]​​​[33]

  • Topiramate. Topiramate is recommended as a first-line option for chronic migraine by the American Headache Society.[33] Subgroup analysis of results from two multi-centre randomised controlled trials in patients with migraine and MOH who did not discontinue the overused medication concluded that topiramate was likely to be effective.[65]​ However, its use can be limited by adverse effects.[10] Note that topiramate should not be used during pregnancy or in women of childbearing potential as it may cause fetal harm.[27]

  • Botulinum toxin type A. The American Headache Society recommends botulinum toxin type A as a first-line option for chronic migraine. It was found to be more effective than placebo in reducing headache days in subgroup analysis of two trials in patients with migraine and MOH who did not discontinue the overused acute medication.[66]​ However, it did not show any added benefit over acute medication discontinuation alone in one randomised trial.[67]​ Note that botulinum toxin type A should be avoided in pregnancy unless essential as there are limited data in pregnant women.

  • Calcitonin gene-related peptide (CGRP) antagonists. Therapies that target CGRP are recommended by the American Headache Society as an option for migraine prevention.[33] Protocols vary, so check local guidance. In the UK, the National Institute for Health and Care Excellence (NICE) recommends CGRP antagonists as an option for migraine prevention only if at least three other preventative medications have been tried and failed.[68][69][70][71][72][73]

    • Oral CGRP antagonists (also known as gepants) - atogepant or rimegepant. These are small molecule CGRP antagonists that are taken orally. Atogepant has been shown to be associated with fewer monthly migraine days and fewer acute medication use days compared with placebo in people with migraine who overuse acute medications.[74][75]

    • CGRP antagonist monoclonal antibodies - these include erenumab, fremanezumab, and galcanezumab (all administered subcutaneously) or eptinezumab (administered intravenously). All four have been found to result in fewer monthly migraine days and lower acute medication use compared with placebo in patients with migraine who overuse acute medications.[76][77][78][79]​ They also have good tolerability, suggesting the possibility of a major role in treatment of MOH, particularly when combined with withdrawal of the overused acute medication.[27][80][81]

    • Note that use of CGRP antagonists should be avoided in pregnancy due to a lack of data.

A meta-analysis of randomised controlled trials that evaluated the relative efficacy of the above medications in patients with MOH against a background of migraine found that:[82]

  • Studies assessing CGRP antagonist monoclonal antibodies included 1982 patients and showed a significant benefit compared with placebo, with a mean reduction of 2.68 migraine days per month (95% CI -3.46 to -1.91) and a 2.90 times higher likelihood (95% CI 2.23 to 3.78) of a ≥50% reduction in migraine or headache days from baseline.

  • Studies assessing botulinum toxin type A included 1139 patients and showed a mean reduction in headache frequency of 1.92 days per month (95% CI -2.68 to -1.16) compared with placebo, although there were uncertainties regarding the likelihood of a ≥50% reduction in migraine or headache days.

  • There was insufficient evidence available to determine the efficacy of topiramate for this purpose.

Ongoing long-term use of the preventative medication, supported by regular follow-up consultations, is important to reduce the risk of relapse into renewed overuse of acute headache medication.[10]

For more detail on preventative strategies, see Migraine in adults.

Primary options

topiramate: 25 mg orally (immediate-release) once daily at bedtime for 1 week initially, increase gradually according to response, maximum 100-200 mg/day in 2 divided doses; 25 mg orally (extended-release) once daily for 1 week initially, increase gradually according to response, maximum 100-200 mg/day

OR

botulinum toxin type A: consult specialist for guidance on dose

Secondary options

atogepant: 60 mg orally once daily

OR

rimegepant: 75 mg orally/sublingually once daily on alternate days

OR

erenumab: 70-140 mg subcutaneously once monthly

OR

fremanezumab: 225 mg subcutaneously once monthly; 675 mg subcutaneously every 3 months

OR

galcanezumab: 240 mg subcutaneously as a single loading dose, followed by 120 mg once monthly

OR

eptinezumab: 100-300 mg intravenously every 3 months

Consider – occipital nerve blockade

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ACUTE
|
adults: uncomplicated
|
with migraine as underlying disorder
Consider – 

occipital nerve blockade

Additional treatment recommended for SOME patients in selected patient group

One small study found that repeated sessions of occipital nerve blockade with lidocaine resulted in better outcomes than acute medication withdrawal alone in patients with MOH associated with triptan overuse.[83]

Consider – non-pharmacological preventative therapy

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ACUTE
|
adults: uncomplicated
|
with migraine as underlying disorder
Consider – 

non-pharmacological preventative therapy

Additional treatment recommended for SOME patients in selected patient group

Non-invasive neuromodulation devices and acupuncture may also be considered as part of the preventative management approach.[10]

Consider – pharmacological preventative therapy

Back
ACUTE
|
adults: uncomplicated
|
with tension-type headache as underlying disorder
Consider – 

pharmacological preventative therapy

Additional treatment recommended for SOME patients in selected patient group

Preventative medication that targets the underlying headache disorder is an important part of the management plan for many patients with MOH.[10][27]​​​

  • In principle, preventative medication can be used: before withdrawal of the overused medication; from the start of withdrawal as part of a combination strategy; or after withdrawal is complete.[10]

  • In practice, the combination approach is often taken, with initiation of a preventative regimen used to facilitate withdrawal from the overused medication(s).

  • A preventative regimen alone may be the best available option if the patient has uncomplicated MOH and is unwilling to discontinue the overused medication.​[9][10]​​ This has been found to be non-inferior to preventative medication with acute medication withdrawal.[54]

If the patient's underlying primary headache disorder is tension-type headache (TTH), target the preventative regimen at that.

  • No evidence is available from controlled trials to inform the most appropriate preventative approach for MOH against a background of TTH.[6]

  • Amitriptyline, started at a low dose and titrated up to an effective dose, is the most commonly used pharmacological option, although its use should be avoided during pregnancy if at all possible.[6][84][85]

  • Mirtazapine and venlafaxine are second-line options but should also be avoided during pregnancy.[85]

Ongoing long-term use of preventative medication, supported by regular follow-up consultations, is important to reduce the risk of relapse into renewed overuse of acute headache medication.[10]

For more detail on preventative strategies for TTH, see Tension-type headache.

Primary options

amitriptyline: 10-25 mg orally once daily at bedtime initially, increase gradually according to response, maximum 150 mg/day

Secondary options

mirtazapine: 15 mg orally once daily at bedtime initially, increase gradually according to response, maximum 30 mg/day

OR

venlafaxine: 37.5 mg orally (extended-release) once daily initially, increase gradually according to response, maximum 150 mg/day

Consider – non-pharmacological preventative therapy

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ACUTE
|
adults: uncomplicated
|
with tension-type headache as underlying disorder
Consider – 

non-pharmacological preventative therapy

Additional treatment recommended for SOME patients in selected patient group

There is evidence to support the effectiveness of relaxation training and cognitive behavioural therapy (CBT) in prevention of chronic TTH and some evidence to suggest benefit from acupuncture.[6][84][85]

adults: complex

1st line – multidisciplinary care and consider hospital admission

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ACUTE
|
adults: complex
1st line – 

multidisciplinary care and consider hospital admission

A holistic, multimodal approach is needed for individuals with complex MOH. Patients with complex MOH are ideally managed by a specialist multidisciplinary team including neurologists or pain specialists and psychologists.[27]

Complex MOH is defined by one or more of: overuse of opioids, barbiturates, benzodiazepines, or other sedatives; the presence of psychiatric or substance abuse comorbidity; a history of relapse following previous treatment for MOH.[10][27]

Consider inpatient care, where available, if:

  • The patient is discontinuing long-term use of an opioid, barbiturate, or benzodiazepine.[10][27][89]​ Careful monitoring of metabolic parameters, blood pressure, fluid balance, and sedation is generally required during withdrawal.[27]

  • The patient has been overusing acute medications from multiple drug classes.

  • The patient has had a prior attempt at medication withdrawal that either failed or resulted in a relapse of MOH.[6][27]​​[57]​​[89]

  • The patient has a significant psychiatric or substance misuse comorbidity.[6][10][89]​​

A combined approach to withdrawal, bridging medication, and preventative medication is taken for complex MOH, using similar principles to those employed for uncomplicated MOH, with the choice of preventative regimen dependent on the underlying primary headache disorder. See the Adults: uncomplicated patient group for details.

  • A gradual taper is recommended for withdrawing opioids, barbiturates, or benzodiazepines.[27][63]​ In some situations, long-acting opioids or phenobarbital may be needed as a transition.[27] This is important for reducing the risk of withdrawal symptoms.[10]

In addition, patients with complex MOH are likely to benefit from additional interventions, such as behavioural interventions to address any anxiety, depression, and suicidality together with pain coping strategies.

  • Overuse of pain medication has a strong behavioural element, and discontinuation involves substantial changes in behaviour and lifestyle.[10]

  • One trial involving 179 patients with uncomplicated MOH found that, compared with minimal behavioural support, maximal behavioural intervention - which consisted of intensive contact with a headache nurse for education, motivational interviewing, and value-based activity planning - significantly reduced acute medication use days, although there was no change in monthly migraine days.[86]

  • Biofeedback and mindfulness have also shown promising results as add-ons to preventative medication.[87][88]

  • Acupuncture and neuromodulation techniques have limited evidence but may also be used.[10]

children and adolescents

1st line – withdrawal from/reduction of acute medication ± rescue medication

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ACUTE
|
children and adolescents
1st line – 

withdrawal from/reduction of acute medication ± rescue medication

There is limited high-quality evidence to inform management of MOH in children and adolescents.[10]​ In practice, the same general treatment strategies used for adults with MOH can be applied to children and adolescents. Education on the importance of reduction of acute medication is a vital aspect of care, and an emphasis on behavioural support is important.[10][90]

Withdrawal of the overused medication is recommended.[91]

  • The few studies published on MOH in children with migraine show a response rate to drug withdrawal (i.e., a >50% reduction in headache frequency) that varies between 40% and 77%.[35][92][93][94]

  • If bridging therapy is needed for withdrawal symptoms, depending on the overused acute medication, options might include a simple analgesic (paracetamol or a non-steroidal anti-inflammatory drug [NSAID]) or a triptan.[95]​ Daily use of naproxen for 1 month to support withdrawal of the overused medication has been suggested as a reasonable strategy.[91]

  • For more detail on bridging therapy options, see acute management in Migraine headache in children or Tension-type headache.

  • If conventional approaches to bridging therapy fail, one group has suggested the following alternative strategies for children and adolescents with MOH:[91]

    • Occipital nerve blockade (with a mix of local anaesthetic and corticosteroid)[91]

    • Hospital admission for a short course of intravenous dihydroergotamine if both simple analgesia (e.g., with naproxen) and occipital nerve blockade prove to be insufficient as bridging therapies to support withdrawal from the overused medication.[91]

Consider – non-pharmacological preventative therapy

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ACUTE
|
children and adolescents
Consider – 

non-pharmacological preventative therapy

Additional treatment recommended for SOME patients in selected patient group

Non-pharmacological preventative strategies are preferred to long-term medication whenever possible. Trigger avoidance is recommended, and behavioural therapies such as cognitive behavioural therapy (CBT) or biofeedback are options.[85][90]​​ Neuromodulation devices have also shown promising early results.[96]

  • Triggers to avoid often include inadequate hydration, skipping meals, poor sleep, and insufficient physical activity.[96]

Consider – pharmacological preventative therapy

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ACUTE
|
children and adolescents
|
with migraine as underlying disorder
Consider – 

pharmacological preventative therapy

Additional treatment recommended for SOME patients in selected patient group

If non-pharmacological approaches are ineffective, preventative medication may become necessary, although evidence is scarce to support this for chronic migraine in children.[90]

Most randomised controlled trials have failed to demonstrate any benefit over placebo.[97]​ Agents that can be considered include propranolol (though not in children with asthma), pizotifen (if available), topiramate (with appropriate cautions over adverse effects), and amitriptyline combined with CBT (with caution around the risk of suicidal thoughts and behaviour).[90] A cautious approach is required, with decision-making shared with patients and carers and regular monitoring of benefit versus potential harm, because evidence is limited and often conflicting.[97]

Oral preventative medications can be poorly tolerated, and botulinum toxin type A and calcitonin gene-related peptide (CGRP) antagonists are not licensed for use in children in most countries.[10]

For more detail on preventative medications, see Migraine headache in children.

Primary options

propranolol: children <35 kg body weight: 10 mg orally once daily initially, increase gradually according to response, maximum 60 mg/day in 3 divided doses; children >35 kg body weight: 20-40 mg orally three times daily

OR

pizotifen: children ≥5 years of age: 0.5 mg orally once daily at bedtime initially, increase gradually according to response, maximum 1.5 mg/day in divided doses (maximum 1 mg/single dose at night)

Secondary options

topiramate: children ≥12 years of age: 25 mg orally (immediate-release) once daily at bedtime for 1 week initially, increase gradually according to response, maximum 100-200 mg/day in 2 divided doses; 25 mg orally (extended-release) once daily for 1 week initially, increase gradually according to response, maximum 100-200 mg/day

OR

amitriptyline: children ≥2 years of age: 0.1 to 0.25 mg/kg orally once daily at bedtime initially, increase gradually according to response, maximum 2 mg/kg/day in 2 divided doses (or 75 mg/day)

Consider – pharmacological preventative therapy

Back
ACUTE
|
children and adolescents
|
with tension-type headache as underlying disorder
Consider – 

pharmacological preventative therapy

Additional treatment recommended for SOME patients in selected patient group

If non-pharmacological approaches are ineffective, preventative medication may become necessary, although evidence is very scarce to support this for tension-type headache in children. Low-dose amitriptyline is sometimes used.[98][99][100]

Primary options

amitriptyline: children ≥2 years of age: 0.1 to 0.25 mg/kg orally once daily at bedtime initially, increase gradually according to response, maximum 2 mg/kg/day in 2 divided doses (or 75 mg/day)

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Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups. See disclaimer

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