Approach

Key Points

  • Education and advice for patients and family members is the first step in managing medication overuse headache (MOH) and may be sufficient on its own to resolve the condition in some patients.

  • Withdrawal from the overused acute medication is an important element of treatment and can be abrupt for ergot derivatives, triptans, and simple analgesics but involves gradual tapering for opioids, barbiturates, or benzodiazepines. Symptomatic treatment for withdrawal symptoms may be needed.

  • Initiation of a preventive regimen is typically used to facilitate withdrawal from the overused medication.

  • Patients with complex MOH require a multidisciplinary approach that includes behavioral interventions and pain coping strategies. Consider inpatient treatment for any patient withdrawing from opioids, barbiturates, or benzodiazepines.

  • Some acute headache medications, such as calcitonin gene-related peptide (CGRP) antagonists or antiemetics, probably do not lead to MOH and should be considered part of the treatment regimen for adults.

​Managing MOH involves a multifaceted approach that includes:[10][27]​​​

  • Patient and family education, including information on the importance of reducing the frequency of the overused medication. In uncomplicated MOH, this may be sufficient on its own.

  • Withdrawal of the overused medication, supported by symptomatic management of any short-term breakthrough headaches that occur during the withdrawal period.

  • Use of appropriate preventive medication targeting the underlying primary headache.

  • Behavioral interventions to address any psychological or medical comorbidities and to maintain adherence to treatment.

Various strategies for managing MOH are used in practice, and there is limited evidence to support the benefits of one over another.[10]

  • There are few double-blind randomized controlled trials specifically looking at different management options for MOH.[10][27] Hence, the selection of treatment regimen is determined less by the strength of evidence and more by individual patient characteristics including comorbidities and the patient's willingness to discontinue the overused medication.[10][27]

  • Evidence is even more scant regarding MOH in children, although the general principles are the same as for adults.[10]

​Commonly used approaches are:[10][27]​​

  • Early discontinuation of the overused medication(s) (either abrupt or tapered) without preventive medication.

  • Early discontinuation of the overused medication(s) (either abrupt or tapered) supported by concurrent preventive medication.

  • Preventive medication together with restricted frequency of use of the overused medication(s).

  • Preventive treatment without actively restricting use of the overused medication(s). In practice, this strategy is generally reserved for patients who are reluctant to withdraw from the acute medication, although evidence suggests it is noninferior to a combination approach.[54]

​Bear in mind that the evidence on the relative benefits of these different management strategies is mixed.[10][27]

  • A multicenter open-label study involving 694 patients from seven countries found that starting preventive medication in parallel with withdrawal of the overused acute medication led to a 44% reduction in headache days in the first month, increasing to 60% after 6 months. Some 68% of the 492 participants who completed the protocol reverted from MOH to an episodic headache pattern.[55]

  • An open-label randomized trial of 120 patients that compared withdrawal of the overused medication alone, preventive medication alone, and a combined strategy of withdrawal plus preventive medication found no difference in reduction of monthly migraine days, acute medication use, or headache intensity.[56]​ However, secondary outcome analysis showed higher rates of reversion from chronic to episodic migraine and greater chance of MOH resolution in the group who had a combination of withdrawal plus preventive medication (74% and 97%, respectively) compared with the preventive medication alone group (60% and 74%) or the withdrawal alone group (42% and 89%).[56]

  • A subsequent, larger pragmatic randomized trial involving 720 participants found that preventive medication alone (with no limitation of the overused medication) was noninferior to the combination of preventive medication plus withdrawal of the overused medication.[54]

Tailoring management to the individual patient: a practical approach

A review by US and European experts has recommended a practical approach to selecting the most appropriate approach for the individual patient.[10]

  • If the patient has uncomplicated MOH and is willing to attempt withdrawal of the overused medication, the recommended approach is a combination of education, discontinuation of the causative medication, and early use of preventive medication.

  • If the patient has uncomplicated MOH and is unwilling to attempt withdrawal of the causative medication, education plus early preventive medication alone can be used. If this approach fails, withdrawal of the causative medication becomes necessary.

  • If the patient has complex MOH, multidisciplinary specialist care is needed, with withdrawal of the overused medication, aggressive use of preventive medication, pain management therapy, and behavioral interventions to support lifestyle change. Complex MOH is defined by the presence of one or more of: use of an opioid, barbiturate, benzodiazepine, or sedative; significant psychiatric comorbidity; a substance misuse or addiction disorder; a history of relapse following previous treatment for MOH. For more detail, see Complex cases, below.

Note that local protocols for MOH are an additional factor that may determine the strategy.

Patient education

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 or simple analgesics, 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] In some patients, this may be sufficient to revert the headache pattern from chronic to episodic (i.e., <15 headache days/month).

  • Advice alone is not appropriate for patients with complex MOH (i.e., they overuse an opioid, barbiturate, or sedative, and/or have experienced previous MOH relapse, and/or have a psychiatric comorbidity).[27] These patients need specialist referral, ideally for multidisciplinary management.[27]

When providing education, ensure 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]​​

  • Explain that MOH is treatable and that restricting or withdrawing the overused medication is a key element.

  • Use open conversation but take care to avoid using language that could be perceived as blaming the patient for excessive use of acute medications.[10]

  • Evidence from randomized trials suggests that a primary care-based education intervention can be highly effective for uncomplicated MOH.[57][58]​​​[59]

Ensure 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][60]​​

Withdrawal/discontinuation of overused 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]​​​

There is no clear consensus on the optimum timing of discontinuation and whether this should be abrupt or gradual.[10][27][62]​​

  • Uncertainty also remains as to whether, in what circumstances, and at what stage of withdrawal preventive medications should be used.[27]

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

Tailor the speed of the withdrawal plan to the individual patient's circumstances.[10]

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

  • 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]

Ensure 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, valproate). Note that valproate must not be used in pregnancy or in women of childbearing potential unless they are following a pregnancy prevention program 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 nonpregnant 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]

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

Preventive treatment

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

  • In principle, preventive 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 preventive regimen used to facilitate withdrawal from the overused medication(s).

A preventive 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 noninferior to preventive medication with acute medication withdrawal.[54]

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

Preventive medication options for migraine

The goal of preventive medication is to target the underlying headache disorder, which is usually migraine or tension-type headache (TTH).[10]

Use one of the following preventive medication options first line 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 multicenter randomized controlled trials in patients with migraine and MOH who did not discontinue the overused medication concluded that topiramate was likely 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]

  • OnabotulinumtoxinA. The American Headache Society recommends onabotulinumtoxinA as a first-line option for chronic migraine.[33] 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 randomized trial.[67]​ Note that onabotulinumtoxinA should generally 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 a first-line option for migraine prevention.[33] Protocols vary, so check local guidance.

    • 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.[68][69]​​​

    • 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.[70][71][72][73]​​​​​​​​ 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][74][75]​​​​​

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

A meta-analysis of randomized controlled trials that evaluated the relative efficacy of the above medications in patients with MOH against a background of migraine found that:[76]

  • 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 onabotulinumtoxinA 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.

Other oral preventive medications, such as beta-blockers, tricyclic antidepressants, valproate, and candesartan (an angiotensin-II receptor antagonist), are also widely used in clinical practice but have not been well studied in MOH and so lack supporting evidence.[10][27]

  • Most patients who need preventive medication as part of specialist MOH management have already failed preventive therapy with beta-blockers, valproate, or amitriptyline.[27]

Nerve blockade, noninvasive neuromodulation devices, and acupuncture may also be considered.[10]

  • 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.[77]

For more detail on preventive approaches to migraine, see Migraine headache in adults.

Preventive medication options for tension-type headache (TTH)

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

If the patient's underlying primary headache disorder is TTH, target the preventive regimen at that.

  • Amitriptyline, started at a low dose and titrated up to an effective dose, is the most commonly used pharmacologic option, although its use should be avoided during pregnancy if at all possible.[6][78][79]​​​​

  • Mirtazapine and venlafaxine are second-line options but should also be avoided during pregnancy.[79]

There is evidence to support the effectiveness of relaxation training and cognitive behavioral therapy (CBT) in prevention of chronic TTH and some evidence to suggest benefit from acupuncture.[6][78][79]

For more detail, see Tension-type headache.

Complex cases

A holistic, multimodal approach is needed for individuals with complex MOH.

  • Complex MOH is often 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]

  • In addition to an aggressive preventive medication regimen, these patients will likely benefit from additional interventions, such as behavioral interventions to address any anxiety, depression, and suicidality together with pain coping strategies.

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

    • One trial involving 179 patients with uncomplicated MOH found that, compared with minimal behavioral support, maximal behavioral 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.[80]

    • Biofeedback and mindfulness have also shown promising results as add-ons to preventive medication.[81][82]​​​

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

Setting of care

Patients with uncomplicated MOH (i.e., those who are overusing simple analgesics, triptans, or ergot derivatives and do not have significant comorbidities) can be successfully managed by primary care physicians.[27]

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

Patients with complex MOH are ideally managed by a specialist multidisciplinary team including neurologists or pain specialists and psychologists.[27]

Consider inpatient care, where available, if:

  • The patient is discontinuing long-term use of an opioid, barbiturate, or benzodiazepine.[10][27][83]​​ 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][60][83]​​​

  • The patient has a significant psychiatric or substance misuse comorbidity.​[6][10][83]

Management of children and adolescents

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 behavioral support is important.[10][84]​​

Medication withdrawal

Withdrawal of the overused medication is recommended.[85]

  • 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][86][87][88]​​​​​​​

  • If bridging therapy is needed for withdrawal symptoms, depending on the overused acute medication, options might include a simple analgesic (acetaminophen or an NSAID) or a triptan.[89][90]​​​ Daily use of naproxen for one month to support withdrawal of the overused medication has been suggested as a reasonable strategy.[85] For more detail on bridging therapy options, see acute management in Migraine headache in children.

  • If conventional approaches to bridging therapy fail, one group has suggested the following alternative strategies for children and adolescents with MOH:[85]

    • Occipital nerve blockade (with a mix of local anesthetic and corticosteroid)[85]

    • Hospital admission for a short course of intravenous dihydroergotamine if both simple analgesia (e.g., naproxen) and occipital nerve blockade prove to be insufficient as bridging therapies to support withdrawal from the overused medication.[85]

Prevention of the underlying headache

Nonpharmacologic preventive strategies are preferred to long-term medication whenever possible. Trigger avoidance is recommended, and behavioral therapies such as cognitive behavioral therapy (CBT) or biofeedback are options.[79][84]​​ Neuromodulation devices have also shown promising early results.[90]

  • Triggers to avoid often include inadequate hydration, skipping meals, poor sleep, and insufficient physical activity.[90]

Evidence is scarce to support preventive medication for chronic migraine in children.[84]

  • Most randomized controlled trials have failed to demonstrate any benefit over placebo.[91]​ Agents that can be considered include propranolol (though not in children with asthma), topiramate (with appropriate cautions over adverse effects), and amitriptyline combined with CBT (with caution around the risk of suicidal thoughts and behavior).[84] A cautious approach is required, with decision-making shared with patients and caregivers and regular monitoring of benefit versus potential harm, because evidence is limited and often conflicting.[91]

  • Oral preventive medications can be poorly tolerated, and onabotulinumtoxinA and CGRP antagonists are not licensed for use in children in most countries.[10]

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

Evidence to support the use of preventive medication is even scarcer for children with chronic TTH.

  • Low-dose amitriptyline is sometimes used.[92][93][94]​​​​​

Management of 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 preventive strategy for the primary headache disorder all important.

Nonpharmacologic strategies are preferred wherever possible. If medication is needed either as part of bridging therapy or the preventive 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 postpartum.[95]

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

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