2/4/2020 Medication overuse headache: Treatment and prognosis - UpToDate

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Medication overuse headache: Treatment and prognosis

Authors: Ivan Garza, MD, Todd J Schwedt, MD, MSCI
Section Editor: Jerry W Swanson, MD, MHPE
Deputy Editor: John F Dashe, MD, PhD

All topics are updated as new evidence becomes available and our peer review process is complete.

Literature review current through: Mar 2020. | This topic last updated: Sep 25, 2019.

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 "Overview of
chronic daily headache".)

APPROACH

Discontinuation of the overused medication is an integral part of the treatment strategy for medication
overuse headache (MOH) [1,2]. It is also important to educate patients about the detrimental effects of
analgesic overuse. Bridge (transitional) therapy may be useful during the immediate post-
discontinuation phase to provide symptomatic relief, although there are only limited supportive data.
For most patients, preventive (prophylactic) therapy aimed at the suspected background primary
headache disorder (eg, migraine) should be included in the treatment strategy for MOH [3]. Screening
and intervening for comorbid psychiatric and substance use disorders is also recommended [3-5].
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Once the overused medications have been discontinued, 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.

PATIENT EDUCATION

Clinicians must educate patients about the detrimental effects of analgesic overuse [1]. Patients need
to understand that analgesics have the potential to cause medication overuse headache (MOH), and
that analgesic overuse can potentially have a negative impact on the effectiveness of some headache
preventive measures [6].

Since most people are not aware of MOH, primary prevention via education and advice is essential
[2]. A national awareness campaign conducted in Denmark reached 10 percent of the population and
improved knowledge about MOH [7].

Several small studies have demonstrated the importance of MOH patient education for reducing
medication intake [8-12]. 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 [8]. 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

The range of short-term benefit following medication discontinuation for patients with medication
overuse headache (MOH) is suggested by the following observations:

A meta-analysis of 17 studies and 1101 patients with MOH defined treatment success as either
no headache at all or a reduction in headache days of >50 percent following withdrawal therapy
[13]. The mean success rate within one to six months after withdrawal was 72 percent.

An uncontrolled prospective study evaluated 175 patients with probable MOH, all of whom
complied with abrupt discontinuation of acute headache medication and a two month medication-

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free period [14]. After the medication-free period, prophylactic treatment was started and follow-
up continued for a mean time of 228 days. Approximately one-half of patients had a significant
reduction in headache frequency with discontinuation of the offending drug. In the remaining 50
percent of patients, who showed no improvement at two months after drug discontinuation, there
was a significant 26 percent decrease in headache frequency after the end of the medication-free
period until the end of the study. The authors concluded that acute medication discontinuation
resulted in a responsive state amenable to prophylactic intervention.

Results from an early observational study suggested that daily concomitant use of analgesic
medications might reduce the effect of prophylactic medications, while discontinuing daily
analgesic medications enhanced the beneficial effect of prophylactic medications [6]. However, in
randomized controlled trials of topiramate, onabotulinumtoxinA, and erenumab, prophylactic
therapy was similarly effective in patients who were overusing medications and those who were
not [15-22]. Further investigations are required to validate these findings and to determine if they
extend to other prophylactic therapies.

Outpatient and inpatient strategies — Withdrawal of overused acute medications can be

accomplished on an outpatient or inpatient basis [3]. Most patients can be managed as outpatients.
Outpatient discontinuation is particularly appropriate for patients who are highly motivated and are not
taking barbiturates or tranquilizers frequently [23].

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 [24]. 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 [25]. Some experts favor inpatient withdrawal
with close observation and medical monitoring in the first several days [26]. 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 family 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 [4,26].

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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 [3]:

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

• Discontinue the overused medication abruptly and provide rescue abortive therapy that can
be used no more than two days per week and is preferably from a medication class that is
different than the overused medication, or

• Instruct the patient to gradually taper the use of acute headache medication as their
headache frequency decreases in response to the effective preventive therapy

For patients who are expected to be unsuccessful with the strategy of abrupt discontinuation of the
overused medication combined with rescue abortive therapy and preventive 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.)

A two-month detoxification followed by preventive treatment only if indicated could be an alternative

strategy in some. 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 [27]. 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.

Discontinuation of barbiturates, opioids, or benzodiazepines — With overuse of barbiturates,

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

For patients withdrawing from 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

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recommended maximum, the initial phenobarbital dose should not exceed 90 mg and can be
tapered by 30 mg every two to three days [28].

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 withdrawal of these agents. (See 'Bridge therapy' below.)

An inpatient protocol originally suggested for transformed migraine with medication overuse is as
follows [3]:

Withdraw 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 analgesic withdrawal, the headaches are likely to
exacerbate before subsequently improving [3]. In addition to increased headache, withdrawal
symptoms can include nausea, vomiting, restlessness, anxiety, nervousness, and disturbed sleep
[3,13]. Withdrawal symptoms typically last 2 to 10 days [13], but occasionally can persist for as long
as two to four weeks [3].

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) [29]. Overall, withdrawal from triptan-induced MOH was less severe than withdrawal
from other analgesics.

BRIDGE THERAPY
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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 suggested for patients who, in the clinician's opinion, are unlikely to be successful
with a treatment plan consisting of discontinuing the overused medication along with rescue therapy
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, lidocaine, valproic
acid, aspirin) medications.

The data supporting these strategies are largely from case series, retrospective chart reviews,
prospective uncontrolled studies, and expert opinion [3]. 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 [30]. 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 medication overuse headache (MOH) on an outpatient
basis [31]. 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.

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One suggested bridge therapy regimen is naproxen 550 mg twice daily for two to four weeks while the
overused acute medication is withdrawn [3]. An alternative is naproxen 550 mg twice daily for one
week, and then naproxen 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) [32]. 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 [33].

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 [34]. According to 2011 European guidelines, however,
prednisone at a dose of at least 60 mg is possibly effective in the treatment of withdrawal symptoms
[35]. 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 [3,36,37].

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 [38,39]. 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

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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 [40].

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) [41]. 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 who had chronic daily headache [42]. 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) [43]. 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 [42]. 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

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(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 [43].
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 [44].

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 [44]. 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.

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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) [44]. 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 [45]. 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 [46]. 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

Whether preventive headache medication should be started at the time of analgesic discontinuation,
after discontinuation, or before discontinuation is controversial and data are limited [23,25]. Since
most patients will require long-term preventive therapy, we suggest starting such treatment at the time
of offending medication withdrawal or even before, in agreement with available guidelines and the
conclusions of a 2016 systematic review [35,47].

In contrast, other authors argue that a preventive drug is unlikely to help during acute analgesic
withdrawal, and note that some patients with medication overuse headache (MOH) will not need a
prophylactic agent after successful withdrawal [25].

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In a retrospective study of 43 children (6 to 17 years old) with chronic daily headache and
medication overuse, 20 were treated with daily doses of a preventive medication, while 23
received no preventive medication [48]. At one month after withdrawal of analgesics, the
proportion of children with a ≥90 percent reduction in headache was similar for those treated or
not treated with daily preventive medication (57 and 50 percent, respectively). The authors
concluded that the concurrent use of preventive agents was not necessary during analgesic
withdrawal in children with medication overuse headache (MOH), but that such agents could be
added if headaches persist after one month [48].

A nonrandomized open-label study compared two outpatient treatment methods and assigned
patients with MOH to either early discontinuation of the overused medication plus prophylactic
medication or discontinuation of the overused medication plus a multidisciplinary educational
program (consisting of six two-hour sessions for groups of up to seven patients) with no
prophylactic medication [49]. Among 86 subjects with MOH who completed one year of follow-up,
the proportion "cured" (ie, no longer overusing medications) was similar for the early
discontinuation/prophylactic medication group and the early discontinuation/multidisciplinary
education group (85 versus 80 percent). Headache frequency was reduced by >50 percent in
similar proportions of participants (approximately 49 percent) in both groups.

Some experts argue and evidence suggests that early discontinuation of the overused medication,
prior to starting preventive medication or at the same time as starting preventive medication, is
unnecessary [50]. 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
abortive medications. Supporting evidence comes from a prospective, open-label investigation of 56
adults with MOH who were randomly 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) [51]. By intention-to-treat analysis 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 [52]. Although these studies provide low quality evidence, they suggest that
both discontinuation of the overused medication (without prophylaxis therapy) and prophylaxis

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therapy (without discontinuation) are associated with short- and long-term improvements in headache
frequency, and that both treatment methods are better than no intervention [51,52].

Furthermore, data from randomized controlled trials investigating topiramate, onabotulinumtoxinA,

and erenumab therapy for chronic migraine have demonstrated that patients have improvements in
migraine patterns even when they are not instructed to discontinue the overused medication [15-22].
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 [21].
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 [21]. Outcomes for subjects
overusing medications at baseline were very similar to the outcomes that included participants with
and without medication overuse.

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 clearly indicated so as to reduce medication
side effects and toxicities.

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 [53].

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 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".)

FOLLOW-UP AND RELAPSE PREVENTION

It is important to establish or maintain follow-up after the overused medications have been stopped
[3]. 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.

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Long acting nonsteroidal anti-inflammatory drugs (NSAIDs) such as naproxen sodium or ketoprofen
are favored for the treatment of mild headaches [3]. 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 medication overuse headache (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 to three or fewer days a month, and NSAIDs to 14 or fewer days a month to prevent MOH
[54]. 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.

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 medication overuse headache (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
[13]. (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 [55]. 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

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MOH undergoing withdrawal therapy found that a high baseline headache frequency predicted
MOH relapse requiring another withdrawal treatment at one year [56].

In a prospective study of 96 patients with MOH, complete data sets at four years were available
for 75 patients [57]. The relapse rate at six months, one year, and four years was 31, 41, and 45
percent, respectively [57]. 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
[58]. 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) [59].
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).

INFORMATION FOR PATIENTS

UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The
Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and
they answer the four or five key questions a patient might have about a given condition. These articles
are best for patients who want a general overview and who prefer short, easy-to-read materials.
Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These
articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth
information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-
mail these topics to your patients. (You can also locate patient education articles on a variety of
subjects by searching on "patient info" and the keyword(s) of interest.)

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

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SUMMARY AND RECOMMENDATIONS

The following are the basic steps in the management of medication overuse headache (MOH):

• Patient education (see 'Patient education' above)

• Discontinuation of the offending medication (see 'Discontinuation of the overused medication'

above)

• Bridge (transitional) therapy, when necessary, aimed at symptomatic relief during medication
withdrawal (see 'Bridge therapy' above)

• Establishment of a headache treatment regimen covering acute and preventive care

appropriate for the underlying primary headache disorder (see 'Preventive therapy' above)

• Follow up and relapse prevention (see 'Follow-up and relapse prevention' above)

It is important to educate patients about the detrimental effects of analgesic overuse, particularly
that analgesics have the potential to cause MOH. (See 'Patient education' above.)

For most patients with MOH, we suggest abrupt discontinuation of the offending medication
rather than a gradual taper (Grade 2C). This can usually be managed in the outpatient setting.
For patients who are unwilling or unable to abruptly discontinue the overused medication,
preventive therapy with a gradual taper off of the overused medication is suggested. (See
'Outpatient and inpatient strategies' above.)

With overuse of barbiturates, opioids, or benzodiazepines, the pace of withdrawal depends on

the amount and frequency of usage. Abrupt discontinuation is done routinely in clinical practice if
the dosage and/or frequency of administration are not too high. However, we suggest a gradual
taper when these agents (particularly barbiturates or benzodiazepines) are being used frequently
or at high doses (Grade 2C). The taper can usually be accomplished in two to four weeks. When
butalbital is stopped abruptly or when high doses are being used, we suggest a phenobarbital
taper for seizure prophylaxis (Grade 2C). Our suggested regimen is to treat with 30 mg of
phenobarbital per day for every 100 mg of butalbital that was being used and to taper
phenobarbital by 30 mg every two to three days until stopped. (See 'Outpatient and inpatient
strategies' above.)

When there is concern for opioid withdrawal symptoms, we suggest treatment with a clonidine
patch for one to two weeks (Grade 2C). (See 'Outpatient and inpatient strategies' above.)

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Inpatient discontinuation withdrawal with medical monitoring in the first several days may be
preferred for some patients who have been using high doses of barbiturates, opioids, and
benzodiazepines. Inpatient management may also be preferable for patients with weak social
support, medical or psychiatric comorbidities, and poor motivation, and for those who have
previously failed outpatient drug withdrawal. (See 'Outpatient and inpatient strategies' above.)

For patients who are unlikely to be successful with discontinuing the overused medication when
combined with preventive and rescue therapy, we suggest bridge therapy. (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)

For patients with MOH and an identified underlying primary headache disorder (eg, migraine or
tension-type headache), we suggest starting preventive treatment at the same time as
withdrawing the offending medication (Grade 2C). (See 'Preventive therapy' above.)

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.)

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