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Medication overuse headache: Treatment and prognosis

Medication overuse headache: Treatment and prognosis
Literature review current through: Jan 2024.
This topic last updated: May 16, 2022.

INTRODUCTION — Chronic daily headache is a descriptive term that encompasses several different specific headache diagnoses. Chronic daily headache types of long duration (ie, four hours or more) include chronic migraine, chronic tension-type headache, medication overuse headache, hemicrania continua, and new daily persistent headache.

Medication overuse headache (MOH) is a common problem in clinical practice that needs to be properly managed in order to increase the likelihood of successful chronic daily headache treatment.

This topic will review the treatment and prognosis of MOH. Other clinical aspects of MOH are discussed elsewhere. (See "Medication overuse headache: Etiology, clinical features, and diagnosis".)

The remaining subtypes of chronic daily headache are reviewed separately. (See "Chronic daily headache: Associated syndromes, evaluation, and management".)

TREATMENT APPROACH — Our approach to the management of MOH starts with patient education on the rationale for treatment. Pharmacotherapy involves initiating effective preventive therapy and discontinuing the overused medication [1-3]. For most patients, we start preventive therapy at the same time as or prior to discontinuing the overused medication and add a temporary symptomatic (rescue) medication for breakthrough pain [4,5]. Follow-up to monitor efficacy of treatment is important to help prevent relapse.

PATIENT EDUCATION — Clinicians must educate patients about the detrimental effects of medication overuse [1]. Patients need to understand that some medications used for the acute treatment of headache have the potential to cause MOH and that overuse can potentially worsen headache symptoms and lead to medication adverse effects or toxicities [2].

Since most people are not aware of MOH, primary prevention via education and advice is essential [3]. A national awareness campaign conducted in Denmark reached 10 percent of the population and improved knowledge about MOH [4].

Several small studies have demonstrated the importance of MOH patient education for reducing medication intake [5-9]. One of these was a prospective, unblinded trial of 120 patients with migraine plus MOH who were randomly assigned to either strong advice to discontinue the overused medication or to a structured inpatient or outpatient detoxification program [5]. Patients in all three groups were instructed to stop the overused medication, and all were permitted to use nonsteroidal anti-inflammatory drugs (NSAIDs) or triptans not more than two days a week for symptomatic relief. Approximately 75 percent of patients in all groups successfully discontinued the overused medications. The trial excluded patients who overused agents containing opioids, benzodiazepines, and barbiturates, and those with coexisting medical or psychiatric illness, and the results may not be generalizable to all patients with MOH.

DISCONTINUATION OF THE OVERUSED MEDICATION — Discontinuation of the overused medication or a substantial reduction in the frequency of taking the overused medication is a key component of treating MOH. In a meta-analysis of 17 studies and 1101 patients with MOH, 72 percent reported no headache at all or a reduction in headache days of >50 percent within one to six months following withdrawal therapy [10].

Weaning strategies — For patients with MOH, discontinuation or substantial reduction of the overused medication is a key goal [1,3]. Preventive (prophylactic) therapy aimed at the suspected background primary headache disorder (eg, migraine) is an integral component of the treatment strategy [11]. There are several transitional strategies that may be used to help discontinue the overused medication and reduce headache burden.

Switch from the overused medication to an alternative symptomatic therapy – A rapid wean may be achieved by stopping the overused medication while starting or optimizing preventive therapy and offering an alternative symptomatic medication to be used ≤2 days each week. This strategy may be appropriate for patients at risk for toxicity from the overused medication who are not at risk for withdrawal with abrupt discontinuation. In a systematic review of treatment strategies for MOH, low-quality evidence supported early discontinuation of the overused medications with use of alternative symptomatic and preventive medications [12]. This approach is also supported by evidence from open-label clinical trials [13,14].

Continue the overused medication during initial treatment – Adding effective preventive therapy while initially continuing the overused medication may be appropriate for some patients unable or unwilling to stop the overused medication. This strategy is used when there are not immediate concerns for toxicity or adverse events related to the overused medication. In an open-label trial, 726 patients with MOH were treated with preventive medications and randomized either to continue the overused medication or to switch to another class of medication used ≤2 days/week for symptomatic management [13]. At baseline, patients had a mean of 13 moderate to severe headache days over 4 weeks. By weeks 9 to 12, both groups had fewer moderate to severe headache days. The frequency of moderate to severe headache days was similar for patients who continued the overused medication and those who were switched to a different medication (9.3 versus 9.1). The frequency of moderate to severe headaches during the first two weeks was also similar between groups. However, the prevalence of medication overuse and the mean frequency of days using symptomatic medication by week 12 was lower in the group that was switched to a different medication. Adverse events were similar for both groups.

Add additional temporary medication (bridge therapy) – Bridge therapy consists of adding a medication to reduce the frequency and severity of headaches that occur during the initial period following discontinuation of the overused medication. It is typically used to provide additional symptomatic relief during the initial transition for patients with severe or frequent headaches who are felt to be unlikely to succeed with a treatment plan consisting of discontinuing the overused medication along with symptomatic and preventive therapy. (See 'Bridge therapy' below.)

Bridge (transitional) therapy may be useful to reduce the detrimental effects of analgesic overuse, although there are only limited supportive data. Screening and intervening for comorbid psychiatric and substance use disorders may also help guide therapy [11,15,16].

Discontinue the overused medication before starting prophylactic treatment – Stopping the overused medication for two months without the use of preventive medication is an alternative strategy that has been observed to improve headache burden. We do not use this strategy because patients may have worsening headaches after acutely stopping the overused medication and may be unable to adhere to the protocol.

In an open-label controlled trial, patients with MOH undergoing detoxification over two months were randomly assigned to receive either no acute headache medication or acute medication restricted to two days per week [14]. Of 58 patients who completed six-month follow-up, patients assigned to no acute treatment had a greater reduction in headache days per month (46 versus 22 percent) and a higher rate of reversion to episodic headache (70 versus 42 percent) compared with patients assigned to limited acute treatment two days per week. The number of patients who initiated preventive treatment was similar in both groups. Detoxification without acute treatment was assessed to be the most effective detoxification strategy.

Some observational data suggest that discontinuing acute headache medications may result in a responsive state amenable to prophylactic intervention [2]. In an uncontrolled prospective study of 175 patients with probable MOH who discontinued acute headache medications and complied with a two-month medication-free period before starting prophylactic treatment, approximately one-half had a significant reduction in headache frequency [17]. The remaining 50 percent of patients who showed no initial response at two months improved after onset of prophylactic therapy with a reported 26 percent reduction in headache frequency. However, in several randomized trials, concomitant prophylactic therapy was similarly effective for patients who were overusing medications and those who were not [18-25].

After treatment of MOH, an ongoing headache treatment regimen is needed for acute and preventive therapy since most patients will continue to have intermittent headaches. Close follow-up after discontinuation of the overused medications is imperative to evaluate progress and prevent relapse. (See 'Follow-up and relapse prevention' below.)

Outpatient and inpatient settings — Withdrawal of overused acute medications can be accomplished on an outpatient or inpatient basis [11]. Most patients can be managed as outpatients. Outpatient discontinuation is particularly appropriate for patients who are highly motivated and are not taking frequent barbiturates, opioids, or other potentially addictive medications [26].

A multicenter observational study of patients with MOH compared inpatient detoxification from the overused medication plus administration of alternate medications with outpatient detoxification plus prescription medications [27]. At six months, among those completing the study (n = 257), two-thirds of patients were no longer overusing acute medications and had reverted to an episodic headache pattern (ie, fewer than 15 headache days per month). Inpatient and outpatient strategies were both effective, though there was a higher dropout rate in the outpatient group.

Significant complications may occur as a consequence of drug dependency when withdrawing from opioids, benzodiazepines and barbiturates, and the choice between outpatient and inpatient withdrawal of these agents remains an area of debate [28]. Some experts favor inpatient withdrawal with close observation and medical monitoring in the first several days [29]. However, it is often reasonable to try outpatient treatment first unless serious withdrawal problems develop or are considered likely.

In addition to the number and type of overused substances, variables influencing the choice between outpatient and inpatient management include social support structure, patient motivation, medical stability, presence of coexisting medical illness, psychological and psychiatric comorbidities, and need for patient monitoring during administration of medical therapies [15,29].

Discontinuation of medications other than barbiturates, opioids, or benzodiazepines — Our suggested outpatient approach for discontinuation of overused medications other than for patients using frequent barbiturates, opioids, or benzodiazepines includes [11]:

Start preventive therapy or optimize existing preventive therapy and do one of the following:

Discontinue the overused medication and switch to an alternative medication from a different class. Limit the use of acute medications to no more than two days per week, or

Taper the acute medication gradually as the headache frequency decreases in response to effective preventive therapy

For patients who are expected to be unsuccessful with the strategy of preventive therapy combined with discontinuing the overused medication either by slow taper or by switching to alternative symptomatic therapy, bridge therapy with a long-acting nonsteroidal anti-inflammatory drug (NSAID) or steroid can be added to the treatment regimen. (See 'Bridge therapy' below.)

Discontinuation of barbiturates, opioids, or benzodiazepines — With overuse of barbiturates, opioids, or benzodiazepines, the pace of discontinuation depends on the amount and frequency of usage. Abrupt outpatient withdrawal is routinely done in clinical practice if dosage of the offending agent is not very high. However, we suggest a gradual taper when these agents are being used frequently or at high doses. The taper can usually be accomplished in two to four weeks.

For patients discontinuing butalbital, we suggest a phenobarbital taper for seizure prophylaxis, particularly when butalbital is stopped abruptly or when high doses are being used. Our preferred regimen is 30 mg of phenobarbital per day for every 100 mg of butalbital that was being used, given that each 100 mg of butalbital is pharmacologically equivalent to 30 mg of phenobarbital. Assuming the total daily dose of butalbital is no higher than 300 mg, the recommended maximum, the initial phenobarbital dose should not exceed 90 mg and can be tapered by 30 mg every three to seven days [30].

When there is concern for opioid withdrawal symptoms, treatment with a once-weekly transdermal clonidine patch (0.1 to 0.2 mg/24 hours) for one to two weeks may help.

Bridge therapy with a long-acting NSAID daily and initiation or optimization of preventive therapy is suggested to accompany discontinuation of these agents. (See 'Bridge therapy' below.)

An inpatient protocol originally suggested for transformed migraine with medication overuse is as follows [11]:

Discontinue the overused medication abruptly. However, opioids may need to be tapered rather than abruptly stopped if high doses are being overused.

When there is concern for opioid withdrawal symptoms, treat with a once-weekly transdermal clonidine patch (0.1 to 0.2 mg/24 hours) for one to two weeks; alternatively, clonidine can be given as needed for withdrawal symptoms (0.1 to 0.2 mg three times daily, titrated up or down based on symptoms).

Treat with 30 mg of phenobarbital for every 100 mg of butalbital that was being used, tapering phenobarbital by 30 mg every two to three days until stopped.

Use intravenous bridge therapy (dihydroergotamine plus metoclopramide, prochlorperazine, valproate sodium, or methylprednisolone).

Start or optimize preventive therapy.

Withdrawal symptoms — During the period of acute medication discontinuation, the headaches may worsen before subsequently improving [11]. In addition to increased headache, withdrawal symptoms can include nausea, vomiting, restlessness, anxiety, nervousness, and disturbed sleep [10,11]. Withdrawal symptoms typically last 2 to 10 days [10] but occasionally can persist for as long as two to four weeks [11].

The duration and severity of withdrawal headache depends on the type of overused analgesic. In one prospective study of 95 patients, the mean duration of withdrawal headache was 4.1 days for triptans, 6.7 days for ergots, and 9.5 days for analgesics (most of which were combined with codeine, caffeine, or barbiturates) [31]. Overall, withdrawal from triptan-induced MOH was less severe than withdrawal from other analgesics.

BRIDGE THERAPY — Bridge therapy, also known as transitional therapy, is used to reduce the frequency and severity of headaches that occur during the initial period following discontinuation of the overused medication. Bridge therapy is typically used to provide additional symptomatic relief during the initial transition for patients with severe or frequent headaches who are felt to be unlikely to succeed with a treatment plan consisting of discontinuing the overused medication along with symptomatic and preventive therapy. Although there are inadequate published data to confirm that bridge therapy is effective, strategies that may have some merit include the short-term use of certain oral (naproxen, tizanidine, glucocorticoids) and intravenous (dihydroergotamine, prochlorperazine, valproic acid, aspirin) medications.

The data supporting these strategies are largely from case series, retrospective chart reviews, prospective uncontrolled studies, and expert opinion [11]. No high-quality comparative studies exist regarding the different options for analgesic discontinuation. Given the available data, reviewed below, when bridge therapy is used, we suggest use of either long-acting nonsteroidal anti-inflammatory drugs (NSAIDs), prednisone, or dihydroergotamine (DHE). Antiemetics are also frequently needed in clinical practice.

For inpatient withdrawal, we suggest intravenous bridge therapy using dihydroergotamine plus metoclopramide, prochlorperazine, valproate sodium, or methylprednisolone.

Naproxen — Evidence from two small studies suggests that naproxen is useful as bridge therapy during withdrawal of overused analgesic medications.

In a series of 22 patients, the effect of naproxen for ergotamine withdrawal symptoms was studied during inpatient treatment [32]. Ten patients were given symptomatic medication (antiemetics, analgesics, and hydration) as needed, while 12 patients were treated with naproxen (500 mg twice daily) starting one day before the ergotamine withdrawal was initiated and continuing until the withdrawal was complete. By the eighth day after withdrawal, those on naproxen had significantly less pain, nausea, vomiting, and restlessness.

A second study with 30 subjects treated MOH on an outpatient basis [33]. The regimen involved patient education, abrupt withdrawal of offending medications (analgesics and/or ergotamine and/or caffeine), use of naproxen for symptomatic relief, and prophylactic medication. Improvement with a >75 percent reduction in headache frequency and intensity was observed in 20 patients (67 percent), all of whom remained off analgesics entirely. Improvement with a 50 to 75 percent reduction in headache frequency and intensity was reported in nine patients (30 percent). The results, however, were obtained at 2.5 months of treatment. It is therefore impossible to attribute the benefit to naproxen alone since it is likely that prophylaxis contributed to improved outcomes.

One suggested bridge therapy regimen is naproxen sodium 550 mg twice daily for two to four weeks while the overused acute medication is withdrawn [11]. An alternative is naproxen sodium 550 mg twice daily for one week and then once daily for one week.

Tizanidine plus nonsteroidal anti-inflammatory drugs — Bridge therapy using tizanidine combined with a NSAID may be effective for MOH.

The evidence comes from one retrospective study of a subset of 55 outpatients with transformed migraine and MOH who were treated with tizanidine (started at 2 mg at bedtime) plus a long-acting NSAID (eg, piroxicam, naproxen, ketoprofen sustained release, or celecoxib) [34]. Patients were instructed to stop frequent use of the suspected offending analgesics and to self-administer triptans or dihydroergotamine for severe headache; triptans were not permitted if they were the offending drugs. Tizanidine was titrated up by 2 mg every three to five days until a therapeutic effect or sedation occurred. The mean daily tizanidine dose was 3.6 mg (range 2 to 16 mg). At six weeks, the number of responders (ie, those with no or trivial analgesic use) was 36 patients (65 percent). The treatment protocol was well tolerated. However, the findings are limited by the retrospective design and the concurrent use of triptans and dihydroergotamine.

Glucocorticoids — The utility of oral glucocorticoids for MOH bridge therapy is uncertain. A 2017 meta-analysis of patients with MOH identified four randomized controlled trials comparing prednisone with placebo or celecoxib after medication withdrawal and concluded that there was low to very low quality evidence that prednisone was not beneficial [35].

These limited data suggest that a short course of high-dose oral prednisone (100 mg) has only minimal, if any, benefit for treating withdrawal headache in patients with MOH. In addition, it is not clear whether patients with primary headache types other than migraine (eg, chronic tension-type headache) might benefit from glucocorticoids [36]. According to 2011 European guidelines, however, prednisone at a dose of at least 60 mg is possibly effective in the treatment of withdrawal symptoms [37]. We commonly prescribe 60 mg daily for five days when using prednisone as bridge therapy. Larger randomized controlled trials are needed to clarify the role of glucocorticoid bridge therapy in the management of MOH.

Other glucocorticoid bridge protocols to treat withdrawal headache include intravenous methylprednisolone 100 to 200 mg every 12 hours for two to three days [11,38,39].

Based on the benefit from glucocorticoids observed in status migrainosus, others have used parenteral dexamethasone or hydrocortisone as bridge therapy to break the cycle of rebound headache [40,41]. Dexamethasone (intravenous or intramuscular) can be started at 8 to 20 mg daily in divided doses, rapidly tapering over two to three days. Hydrocortisone can be started intravenously via a saline drip at 100 mg over 10 minutes every 6 hours for the first 24 hours, then tapered to every 8 hours for the second 24 hours, then every 12 hours for the third 24 hours, and then one final dose for the last 24 hours.

Dihydroergotamine — DHE appears to be beneficial as bridge therapy for MOH. Intravenous (IV) DHE is also used as treatment for status migrainosus [42].

Repetitive IV DHE (the "Raskin protocol") was evaluated originally in a 1986 study that treated 55 patients with chronic intractable migraine headache (including 36 dependent on ergotamine, analgesics, diazepam, or glucocorticoids) [43]. These patients received IV DHE and metoclopramide every eight hours. A control group consisted of 54 matched patients (38 drug-dependent) treated with IV diazepam every eight hours. Many of the patients in both groups were overusing opioids and aspirin-caffeine-butalbital preparations. Within 48 hours, 49 DHE-treated patients (89 percent) became headache-free, while only seven diazepam-treated patients (13 percent) became free of headache within three to six days. Since then, other studies have shown benefit of DHE in bridging during analgesic overuse withdrawal.

Repetitive IV DHE was also studied in a retrospective report of 300 patients with refractory headache, including 258 classified as having chronic daily headache (the study preceded the contemporary classification for chronic migraine) [44]. Treatment involved tapering or discontinuation of overused medications (eg, analgesics, barbiturates, caffeine, narcotics, ergots), repetitive IV DHE and metoclopramide, preventive medications, and educational and psychological support. Adjunct medications (methadone, clonidine, phenobarbital, lorazepam, among others) were used for withdrawal symptoms of narcotic, barbiturate, and anxiolytic drugs. In addition to DHE, NSAIDs were given as analgesics during withdrawal. Overall, 91 percent of the patients became headache-free, typically within two to three days. The average duration of hospitalization was 7.4 days.

Continuous IV DHE may be as effective as repetitive IV DHE. In a retrospective study of 171 patients with refractory headache, the headache-free rates were similar after treatment with continuous IV DHE and repetitive IV DHE (92.5 versus 86.5 percent) [45]. The average hospital stay for both treatment groups was four days. The average length of time to become headache-free was approximately three days for both continuous and repetitive IV DHE.

Protocols — DHE can be given intravenously as repetitive or continuous therapy.

Repetitive IV DHE treatment is started with IV metoclopramide (10 mg) given over 30 minutes, followed by a test dose of IV DHE (0.5 mg) over one minute [44]. Therapy is stopped if hypertension, severe nausea, or chest pain occur. Patients who have clinically significant improvement in headache after the test dose are continued on DHE (0.5 mg) every eight hours. Those with persistent headaches without severe nausea are given an additional dose of DHE (0.5 mg) one hour after the first dose, and then DHE (1 mg) every eight hours. Metoclopramide (10 mg) is administered as needed before each infusion of DHE. In patients who have severe nausea, the metoclopramide dose is increased to 20 mg, or the next dose of DHE is decreased to 0.25 mg. The doses of DHE and metoclopramide are adjusted daily based upon headache severity and side effects.

DHE therapy is continued every eight hours until the patient is headache-free. At that point, IV DHE is tapered to every 12 hours for two or three doses, then discontinued if the patient remains headache-free. Thereafter, any breakthrough headaches are treated with IV DHE every eight hours as needed.

Continuous IV DHE is delivered using 3 mg DHE in 1000 mL of normal saline at 42 mL/hr by IV infusion pump, totaling 3 mg of DHE over 24 hours if administered at a constant rate [45]. Metoclopramide (10 mg IV) is given every eight hours as needed for nausea for approximately six doses. Adjustments in DHE dosage are made to alleviate side effects. The delivery of IV DHE is decreased or interrupted if significant nausea, vomiting, leg cramps, diarrhea, or other undesirable symptoms occur. Once these subside, the DHE dose can usually be continued at a decreased but more tolerable rate. As headaches began to diminish, the dose of continuous IV DHE is decreased.

Side effects and contraindications — Significant adverse reactions to DHE include nausea, vomiting, dizziness, and somnolence. Uncommon but important reactions include arterial and coronary vasospasm, hypertension, and ventricular arrhythmias.

DHE is contraindicated in patients with ischemic vascular disease involving the coronary, cerebrovascular, or peripheral circulations. Other contraindications to DHE include pregnancy, uncontrolled hypertension, hemiplegic migraine, migraine with brainstem aura, sepsis, and severe hepatic or renal dysfunction.

Prochlorperazine — Short-term treatment with repetitive IV prochlorperazine may be a useful intervention for patients with chronic daily headache with or without analgesic overuse [46].

In a retrospective study, 135 patients with refractory chronic daily headache, including 95 with analgesic overuse, were treated with IV prochlorperazine 5 to 10 mg every eight hours, with the dose adjusted up to a maximum of 10 mg every six hours (for no longer than two to three days at the maximum dose) according to efficacy and side effects [46]. All analgesics, narcotics, and ergots were discontinued, but preventive medications were maintained or added to the regimen. Oral diphenhydramine (100 mg) was given before sleep to prevent prochlorperazine-related extrapyramidal symptoms (eg, akathisia or dystonia). Prochlorperazine was tapered off by one dose a day if the patient was headache-free or had minimal headache for >24 hours.

After IV prochlorperazine treatment, a ≥50 percent reduction of headache intensity was noted by 121 patients (90 percent), and headache-free status was achieved by 85 (63 percent) [46]. The mean inpatient stay was 6 days (range 3 to 20), and the mean total prochlorperazine used was 98 mg (range 15 to 255 mg). Acute extrapyramidal symptoms occurred in 21 patients (16 percent). These were treated with diphenhydramine or biperiden.

Valproate — Intravenous valproate (divalproex sodium, a valproic acid derivative) may be an option in patients who have contraindications to or have failed treatment with DHE [47]. In an uncontrolled study, 10 patients with chronic daily headache and/or transformed migraine, with or without medication overuse, were treated with IV valproate beginning with a loading dose of 15 mg/kg infused over 30 minutes, followed by maintenance doses of 5 mg/kg infused over 15 minutes every eight hours for 12 to 48 hours. All analgesics and triptans were discontinued prior to treatment with valproate, and preventative medications for migraine were begun or continued. Total or near total resolution of headache was reported by four of the 10 patients, while some improvement in headache was reported by eight.

Aspirin — A single retrospective chart review from the United Kingdom reported that open-label IV aspirin (lysine acetylsalicylate) was effective for short-term pain relief, assessed one to three hours after administration [48]. The study evaluated a series of 168 hospitalized adults with various forms of headache, including 165 with chronic daily headache, 159 who were overusing headache medication at admission, and 129 with a primary headache diagnosis of migraine. IV aspirin (1 g) was given from one to 50 doses (median five). Among 113 patients with available outcome information, the subjective effect of aspirin was considered good, moderate, or absent for 27, 58, and 14 percent of patients, respectively. The treatment was well-tolerated, and no serious adverse events were reported.

IV aspirin is available in Europe and Japan but is not available in the United States.

PREVENTIVE THERAPY — We suggest starting preventive treatment at the time the overused medication is discontinued or even before, in agreement with available guidelines and data from clinical trials as well as a 2016 systematic review [12,37,49]. Most patients will require long-term preventive therapy as part of the strategy to reduce headache burden.

Efficacy – One trial of 102 MOH patients evaluated strategies of withdrawing the overused agent, adding a preventive agent, or withdrawing the overused agent along with adding a preventive agent. The reduction in number of headache days was similar across groups. At six months, however, remission to episodic headaches was more likely in patients in the withdraw-plus-prevention group than those in the withdrawal-only group (74 versus 42 percent) [49].

Some data have shown preventive therapy may improve migraine patterns even when patients are not instructed to discontinue the overused medication [18-25,50-52]. As an example, a secondary analysis of two trials of onabotulinumtoxinA for the treatment of chronic migraine focused on the subgroup of 904 subjects who were overusing medications at baseline [24]. Compared with placebo, onabotulinumtoxinA provided greater reductions in headache days, migraine days, days with moderate/severe headache, headache episodes, number of hours with headache, and the percentage of participants with severe headache-related disability [24]. Outcomes for subjects overusing medications at baseline were very similar to the outcomes that included participants with and without medication overuse.

Other experts argue that early discontinuation of the overused medication, prior to starting preventive medication or at the same time as starting preventive medication, is unnecessary [53]. This argument is based on the notion that once preventive therapy results in reduced headache frequency, patients will naturally reduce the frequency with which they are using acute medications. Supporting evidence comes from a prospective, open-label investigation of 56 adults with MOH who were assigned to either immediate prophylactic treatment without instructions to stop the overused medication (the prophylaxis group), outpatient discontinuation of the overused medication without prophylactic treatment (the withdrawal group), or no specific treatment (the control group) [54]. At three months, the prophylaxis group averaged 7.2 fewer headache days per month (95% CI -2.7 to -11.8), the withdrawal group 4.2 fewer headache days per month (95% CI -3.3 to -7.4), and the control group 1.6 fewer headache days per month (95% CI 1.8 to -5.1). Although the reduction in headache days was most pronounced for the prophylaxis group, the difference between the prophylaxis and withdrawal groups for this outcome measure did not achieve statistical significance. In a subsequent study reporting one- and four-year follow-up data for 50 of these subjects, those in both the prophylaxis and withdrawal groups had sustained reductions in headache frequency compared with baseline, again with no significant differences between the two groups [55]. Although these studies provide low quality evidence, they suggest that both discontinuation of the overused medication (without prophylaxis therapy) and prophylaxis therapy (without discontinuation) are associated with short- and long-term improvements in headache frequency, and that both treatment methods are better than no intervention [54,55].

Regardless of the exact timing with which patients discontinue their overused medication and regardless of whether preventive medication can reduce headache frequency despite medication overuse, discontinuation of the overused medication is indicated to reduce medication side effects and toxicities.

Selection of therapy – Headache preventive therapy should be chosen according to the suspected underlying primary headache disorder (eg, migraine, chronic tension-type headache). Preventive therapy is discussed in detail separately for the major types of primary headache that underlie MOH. (See "Preventive treatment of episodic migraine in adults" and "Chronic migraine" and "Acute treatment of migraine in children" and "Tension-type headache in adults: Preventive treatment" and "Tension-type headache in children" and "Hemicrania continua" and "New daily persistent headache".)

The role of biofeedback in MOH management remains to be determined. However, a small randomized, controlled, single-blind trial found that patients treated with frontal electromyographic (EMG) biofeedback combined with preventive pharmacological therapy were more likely to experience a decrease in headache frequency compared with those getting pharmacological treatment alone [56].

FOLLOW-UP AND RELAPSE PREVENTION — It is important to establish or maintain follow-up after the overused medications have been stopped [11]. Patients frequently return to a pattern of intermittent headaches, which in some individuals may include both full blown migraine attacks and mild to moderate headaches with predominant tension-type features.

Long acting nonsteroidal anti-inflammatory drugs (NSAIDs) such as naproxen sodium or ketoprofen are favored for the treatment of mild headaches [11]. Moderate to severe migraine attacks can be treated with triptans, dihydroergotamine, and/or other migraine abortives. The acute treatment of migraine and tension-type headache is reviewed in detail elsewhere. (See "Acute treatment of migraine in adults" and "Acute treatment of migraine in children" and "Tension-type headache in adults: Acute treatment" and "Tension-type headache in children".)

To prevent the redevelopment of MOH, the frequency of acute symptomatic medication usage should be limited, and the rationale for the restriction should be explained to the patient. The use of triptans, ergotamine-dihydroergotamine, or combination analgesics should be limited to nine or fewer days a month on average, butalbital-containing analgesics should be used sparingly, and dosing limited to three or fewer days a month and NSAIDs to 14 or fewer days a month to prevent MOH [57]. The more restrictive limits on butalbital-containing analgesics are due to their high potential for MOH. In general, it is best to avoid the use of opioids and/or butalbital for the regular management of primary headache disorders. Calcitonin gene-related peptide antagonists and non-invasive neuromodulation are acute treatment options that are not likely to be associated with MOH [58].

Proper treatment of MOH and relapse prevention requires recognition of the elements that may contribute to and underlie its development and perpetuation. Coexistent anxiety should be properly managed if present. (See "Medication overuse headache: Etiology, clinical features, and diagnosis", section on 'Biobehavioral factors'.)

PROGNOSIS — The long-term success of withdrawal from MOH depends, in part, on the type of primary headache and the type of overused medication. Most relapses happen in the first year after withdrawal. These points are illustrated by the following reports:

As noted earlier, a meta-analysis of 17 studies and 1101 patients with MOH found that the success rate for withdrawal therapy at one to six months was 72 percent, where treatment success was defined as either no headaches or a reduction in headache days of >50 percent [10]. (See 'Discontinuation of the overused medication' above.)

In a study with prospective data collected from 240 patients with MOH who were treated with drug withdrawal and preventive therapy, the one-year rate of treatment success (defined as absence of chronic headache and medication overuse) was 57 percent [59]. Independent predictors of unfavorable treatment outcome at one year were a higher frequency of primary headache, ergotamine overuse, and a greater degree of headache-related disability at the time of MOH diagnosis. Similarly, a longitudinal study of hospitalized patients with chronic migraine and MOH undergoing withdrawal therapy found that a high baseline headache frequency predicted MOH relapse requiring another withdrawal treatment at one year [60].

In a prospective study of 96 patients with MOH, complete data sets at four years were available for 75 patients [61]. The relapse rate at six months, one year, and four years was 31, 41, and 45 percent, respectively [61]. Patients with underlying migraine headache had a lower relapse rate than those with tension-type headache or combined migraine and tension-type headache, but small numbers prevent definitive conclusions.

In a retrospective report that analyzed outcomes for 67 patients with MOH after multidisciplinary headache treatment at a tertiary center, the reduction in total headache frequency for those with underlying tension-type headache and those with underlying migraine was 50 and 72 percent [62]. These findings suggest that patients with background migraine have a better outcome following withdrawal from MOH than those with underlying tension-type headache.

Outcome at one year after MOH treatment may be a reliable predictor of long-term remission and could be an important time to detect those at risk of MOH relapse. In a prospective cohort study at a specialized headache center, 240 patients with MOH were treated and included in a one-year follow-up study and then subsequently followed for up to 10 or more years (median follow-up 3 years) [63]. At the end of follow-up, approximately 43 percent were in remission. The most important predictors of remission were lower number of headache days per month at one year (hazard ratio [HR] 0.94, 95% CI 0.88-0.99) and efficient initial drug withdrawal (HR 0.14, 95% CI 0.04-0.44).

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Beyond the Basics topics (see "Patient education: Headache treatment in adults (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

Treatment approach – Our approach to the management of medication overuse headache (MOH) involves patient education on the rationale for treatment, initiation of effective preventive therapy, discontinuation of the overused medication, and follow-up to prevent relapse. (See 'Treatment approach' above.)

Strategies for discontinuing the overused medication – For patients with MOH, discontinuation or substantial reduction of the overused medication is a key goal. In most instances, the choice of discontinuation strategy depends on patient preference and involves shared decision-making. (See 'Discontinuation of the overused medication' above.)

Abrupt discontinuation involves stopping the overused medication while starting or optimizing preventive therapy and offering an alternative symptomatic medication to be used ≤2 days each week. This strategy may be appropriate for patients at risk for toxicity from the overused medication who are not at risk for withdrawal with abrupt discontinuation. (See 'Weaning strategies' above.)

A slow taper may be used after a transition of initially continuing the overused medication until symptoms improve with effective preventive therapy. This strategy may be appropriate for patients unable or unwilling to stop the overused medication when there are not immediate concerns for toxicity or adverse events and for patients taking barbiturates, opioids, or benzodiazepines who are at risk for withdrawal with abrupt discontinuation. (See 'Weaning strategies' above.)

For patients taking barbiturates, opioids, or benzodiazepines frequently or at high doses, we suggest a slow taper over two to four weeks rather than abrupt discontinuation (Grade 2C). For patients discontinuing butalbital, we use phenobarbital at 30 mg daily for each 100 mg of butalbital that was being used and taper phenobarbital by 30 mg every two to three days. For patients discontinuing opioids who are at risk for withdrawal symptoms, we used a clonidine patch for one to two weeks. (See 'Discontinuation of barbiturates, opioids, or benzodiazepines' above.)

Bridge therapy – For patients with severe and/or frequent headaches who are unlikely to be successful with discontinuing the overused medication when combined with preventive and symptomatic therapy, we suggest adding bridge therapy (Grade 2C). (See 'Bridge therapy' above.)

For outpatients, our preferred choices for bridge therapy are long-acting nonsteroidal anti-inflammatory drugs (NSAIDs; eg, naproxen) or oral prednisone. (See 'Naproxen' above and 'Glucocorticoids' above.)

For inpatients, our preferred choices for bridge therapy are intravenous dihydroergotamine plus metoclopramide, intravenous prochlorperazine, intravenous valproate, or intravenous methylprednisolone. (See 'Dihydroergotamine' above and 'Prochlorperazine' above and 'Valproate' above and 'Glucocorticoids' above.)

Preventive therapy – For patients with MOH, we suggest starting preventive treatment before or at the same time as withdrawing the overused medication (Grade 2C). (See 'Preventive therapy' above.)

Preventing relapse – To prevent MOH relapse, triptan, ergotamine-dihydroergotamine, or combination analgesic use should be limited to nine or fewer days a month on average and NSAIDs to 14 or fewer days a month. Butalbital-containing analgesics and opioids should be avoided because of their high risk for MOH. (See 'Follow-up and relapse prevention' above.)

  1. Abrams BM. Medication overuse headaches. Med Clin North Am 2013; 97:337.
  2. Mathew NT, Kurman R, Perez F. Drug induced refractory headache--clinical features and management. Headache 1990; 30:634.
  3. Diener HC, Dodick D, Evers S, et al. Pathophysiology, prevention, and treatment of medication overuse headache. Lancet Neurol 2019; 18:891.
  4. Carlsen LN, Westergaard ML, Bisgaard M, et al. National awareness campaign to prevent medication-overuse headache in Denmark. Cephalalgia 2018; 38:1316.
  5. Rossi P, Di Lorenzo C, Faroni J, et al. Advice alone vs. structured detoxification programmes for medication overuse headache: a prospective, randomized, open-label trial in transformed migraine patients with low medical needs. Cephalalgia 2006; 26:1097.
  6. Lagman-Bartolome AM, Lawler V, Lay C. Headache Education Active-Waiting Directive: A Program to Enhance Well-Being During Long Referral Wait Times. Headache 2018; 58:109.
  7. Kristoffersen ES, Straand J, Vetvik KG, et al. Brief intervention by general practitioners for medication-overuse headache, follow-up after 6 months: a pragmatic cluster-randomised controlled trial. J Neurol 2016; 263:344.
  8. Grande RB, Aaseth K, Benth JŠ, et al. Reduction in medication-overuse headache after short information. The Akershus study of chronic headache. Eur J Neurol 2011; 18:129.
  9. Rossi P, Faroni JV, Nappi G. Short-term effectiveness of simple advice as a withdrawal strategy in simple and complicated medication overuse headache. Eur J Neurol 2011; 18:396.
  10. Diener HC, Limmroth V. Medication-overuse headache: a worldwide problem. Lancet Neurol 2004; 3:475.
  11. Boes CJ, Black DF, Dodick DW. Pathophysiology and management of transformed migraine and medication overuse headache. Semin Neurol 2006; 26:232.
  12. Chiang CC, Schwedt TJ, Wang SJ, Dodick DW. Treatment of medication-overuse headache: A systematic review. Cephalalgia 2016; 36:371.
  13. Schwedt TJ, Hentz JG, Sahai-Srivastava S, et al. Patient-Centered Treatment of Chronic Migraine With Medication Overuse: A Prospective, Randomized, Pragmatic Clinical Trial. Neurology 2022; 98:e1409.
  14. Carlsen LN, Munksgaard SB, Jensen RH, Bendtsen L. Complete detoxification is the most effective treatment of medication-overuse headache: A randomized controlled open-label trial. Cephalalgia 2018; 38:225.
  15. Dodick D, Freitag F. Evidence-based understanding of medication-overuse headache: clinical implications. Headache 2006; 46 Suppl 4:S202.
  16. Bottiroli S, Allena M, Sances G, et al. Psychological, clinical, and therapeutic predictors of the outcome of detoxification in a large clinical population of medication-overuse headache: A six-month follow-up of the COMOESTAS Project. Cephalalgia 2019; 39:135.
  17. Zeeberg P, Olesen J, Jensen R. Discontinuation of medication overuse in headache patients: recovery of therapeutic responsiveness. Cephalalgia 2006; 26:1192.
  18. Diener HC, Bussone G, Van Oene JC, et al. Topiramate reduces headache days in chronic migraine: a randomized, double-blind, placebo-controlled study. Cephalalgia 2007; 27:814.
  19. Silberstein SD, Lipton RB, Dodick DW, et al. Efficacy and safety of topiramate for the treatment of chronic migraine: a randomized, double-blind, placebo-controlled trial. Headache 2007; 47:170.
  20. Diener HC, Dodick DW, Goadsby PJ, et al. Utility of topiramate for the treatment of patients with chronic migraine in the presence or absence of acute medication overuse. Cephalalgia 2009; 29:1021.
  21. Aurora SK, Dodick DW, Turkel CC, et al. OnabotulinumtoxinA for treatment of chronic migraine: results from the double-blind, randomized, placebo-controlled phase of the PREEMPT 1 trial. Cephalalgia 2010; 30:793.
  22. Diener HC, Dodick DW, Aurora SK, et al. OnabotulinumtoxinA for treatment of chronic migraine: results from the double-blind, randomized, placebo-controlled phase of the PREEMPT 2 trial. Cephalalgia 2010; 30:804.
  23. Dodick DW, Turkel CC, DeGryse RE, et al. OnabotulinumtoxinA for treatment of chronic migraine: pooled results from the double-blind, randomized, placebo-controlled phases of the PREEMPT clinical program. Headache 2010; 50:921.
  24. Silberstein SD, Blumenfeld AM, Cady RK, et al. OnabotulinumtoxinA for treatment of chronic migraine: PREEMPT 24-week pooled subgroup analysis of patients who had acute headache medication overuse at baseline. J Neurol Sci 2013; 331:48.
  25. Tepper SJ, Diener HC, Ashina M, et al. Erenumab in chronic migraine with medication overuse: Subgroup analysis of a randomized trial. Neurology 2019; 92:e2309.
  26. Katsarava Z, Jensen R. Medication-overuse headache: where are we now? Curr Opin Neurol 2007; 20:326.
  27. Tassorelli C, Jensen R, Allena M, et al. A consensus protocol for the management of medication-overuse headache: Evaluation in a multicentric, multinational study. Cephalalgia 2014; 34:645.
  28. Obermann M, Katsarava Z. Management of medication-overuse headache. Expert Rev Neurother 2007; 7:1145.
  29. Freitag FG, Lake A 3rd, Lipton R, et al. Inpatient treatment of headache: an evidence-based assessment. Headache 2004; 44:342.
  30. Young W, Silberstein S, Nahas S, Marmura M. Jefferson Headache Manual, Demos Medical Publishing, New York 2010.
  31. Katsarava Z, Fritsche G, Muessig M, et al. Clinical features of withdrawal headache following overuse of triptans and other headache drugs. Neurology 2001; 57:1694.
  32. Mathew NT. Amelioration of ergotamine withdrawal symptoms with naproxen. Headache 1987; 27:130.
  33. 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 1993; 8:212.
  34. Smith TR. Low-dose tizanidine with nonsteroidal anti-inflammatory drugs for detoxification from analgesic rebound headache. Headache 2002; 42:175.
  35. de Goffau MJ, Klaver ARE, Willemsen MG, et al. The Effectiveness of Treatments for Patients With Medication Overuse Headache: A Systematic Review and Meta-Analysis. J Pain 2017; 18:615.
  36. Diener HC. How to treat medication-overuse headache: prednisolone or no prednisolone? Neurology 2007; 69:14.
  37. Evers S, Jensen R, European Federation of Neurological Societies. Treatment of medication overuse headache--guideline of the EFNS headache panel. Eur J Neurol 2011; 18:1115.
  38. Young WB. Medication Overuse Headache. Curr Treat Options Neurol 2001; 3:181.
  39. Rozen TD. Migraine Headache: Immunosuppressant Therapy. Curr Treat Options Neurol 2002; 4:395.
  40. Krymchantowski AV, Barbosa JS. Prednisone as initial treatment of analgesic-induced daily headache. Cephalalgia 2000; 20:107.
  41. Silberstein SD, Saper JR, Freitag FG. Migraine: diagnosis and treatment. In: Wolff's Headache and Other Head Pain, Silberstein SD, Lipton RB, Dalessio DJ (Eds), Oxford University Press, New York 2001. p.121.
  42. Silberstein SD. Practice parameter: evidence-based guidelines for migraine headache (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 2000; 55:754.
  43. Raskin NH. Repetitive intravenous dihydroergotamine as therapy for intractable migraine. Neurology 1986; 36:995.
  44. Silberstein SD, Schulman EA, Hopkins MM. Repetitive intravenous DHE in the treatment of refractory headache. Headache 1990; 30:334.
  45. Ford RG, Ford KT. Continuous intravenous dihydroergotamine in the treatment of intractable headache. Headache 1997; 37:129.
  46. Lu SR, Fuh JL, Juang KD, Wang SJ. Repetitive intravenous prochlorperazine treatment of patients with refractory chronic daily headache. Headache 2000; 40:724.
  47. Schwartz TH, Karpitskiy VV, Sohn RS. Intravenous valproate sodium in the treatment of daily headache. Headache 2002; 42:519.
  48. Weatherall MW, Telzerow AJ, Cittadini E, et al. Intravenous aspirin (lysine acetylsalicylate) in the inpatient management of headache. Neurology 2010; 75:1098.
  49. Carlsen LN, Munksgaard SB, Nielsen M, et al. Comparison of 3 Treatment Strategies for Medication Overuse Headache: A Randomized Clinical Trial. JAMA Neurol 2020; 77:1069.
  50. Dodick DW, Doty EG, Aurora SK, et al. Medication overuse in a subgroup analysis of phase 3 placebo-controlled studies of galcanezumab in the prevention of episodic and chronic migraine. Cephalalgia 2021; 41:340.
  51. Diener HC, Marmura MJ, Tepper SJ, et al. Efficacy, tolerability, and safety of eptinezumab in patients with a dual diagnosis of chronic migraine and medication-overuse headache: Subgroup analysis of PROMISE-2. Headache 2021; 61:125.
  52. Silberstein SD, Cohen JM, Seminerio MJ, et al. The impact of fremanezumab on medication overuse in patients with chronic migraine: subgroup analysis of the HALO CM study. J Headache Pain 2020; 21:114.
  53. Diener HC. Detoxification for medication overuse headache is not necessary. Cephalalgia 2012; 32:423.
  54. Hagen K, Albretsen C, Vilming ST, et al. Management of medication overuse headache: 1-year randomized multicentre open-label trial. Cephalalgia 2009; 29:221.
  55. Hagen K, Stovner LJ. A randomized controlled trial on medication-overuse headache: outcome after 1 and 4 years. Acta Neurol Scand Suppl 2011; :38.
  56. Rausa M, Palomba D, Cevoli S, et al. Biofeedback in the prophylactic treatment of medication overuse headache: a pilot randomized controlled trial. J Headache Pain 2016; 17:87.
  57. Garza I, Swanson JW. Answers to frequently asked questions about migraine. Mayo Clin Proc 2006; 81:1387.
  58. Saengjaroentham C, Strother LC, Dripps I, et al. Differential medication overuse risk of novel anti-migraine therapeutics. Brain 2020; 143:2681.
  59. Zidverc-Trajkovic J, Pekmezovic T, Jovanovic Z, et al. Medication overuse headache: clinical features predicting treatment outcome at 1-year follow-up. Cephalalgia 2007; 27:1219.
  60. Raggi A, Giovannetti AM, Leonardi M, et al. Predictors of 12-Months Relapse After Withdrawal Treatment in Hospitalized Patients With Chronic Migraine Associated With Medication Overuse: A Longitudinal Observational Study. Headache 2017; 57:60.
  61. Katsarava Z, Muessig M, Dzagnidze A, et al. Medication overuse headache: rates and predictors for relapse in a 4-year prospective study. Cephalalgia 2005; 25:12.
  62. Zeeberg P, Olesen J, Jensen R. Efficacy of multidisciplinary treatment in a tertiary referral headache centre. Cephalalgia 2005; 25:1159.
  63. Zidverc-Trajkovic JJ, Pekmezovic T, Jovanovic Z, et al. Long-term predictors of remission in patients treated for medication-overuse headache at a specialized headache center: A prospective cohort study. Cephalalgia 2016.
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