Medication Overuse (Rebound) Headaches
Neurology. 2006 Jul
11;67(1):109-13.
Medication-overuse headache in patients with cluster headache.
Paemeleire K, Bahra A, Evers S, Matharu MS, Goadsby PJ.
Headache Group, Institute of Neurology, Queen Square, London, UK.
OBJECTIVE: Medication-overuse headache (MOH) in cluster headache (CH) patients is incompletely described, perhaps because of the relatively low prevalence of CH. METHODS: The authors describe a retrospective series of 17 patients (13 men, 4 women) with CH who developed MOH in association with overuse of a wide range of monotherapies or varying combinations of simple analgesics (n = 9), caffeine (n = 1), opioids (n = 10), ergotamine (n = 3), and triptans (n = 14). The series includes both episodic (n = 7) and chronic (n = 10) CH patients. RESULTS: A specific triptan-overuse headache diagnosis was made in 3 patients, an opioid-overuse headache diagnosis was made in 1 patient, and an ergotamine-overuse headache diagnosis was made in 1 patient. In approximately half of the patients (n = 8), the MOH phenotype was a bilateral, dull, and featureless daily headache. In the other 9 patients, the MOH was characterized by at least one associated feature, most commonly nausea (n = 6), exacerbation with head movement (n = 5), or throbbing character of the pain (n = 5). The common denominator in 15 patients was a personal or family history, or both, of migraine. The 2 other patients gave a family history of unspecified headaches. Medication withdrawal was attempted and successful in 13 patients. CONCLUSIONS: Medication-overuse headache is a previously underrecognized and treatable problem associated with cluster headache (CH). CH patients should be carefully monitored, especially those with a personal or family history of migraine.
PMID: 16832088
Funct Neurol. 2000 Jul-Sep;15(3):167-70
Sumatriptan overuse in episodic cluster headache: lack of adverse events, rebound syndromes, drug dependence and tachyphylaxis.
Centonze
V, Bassi A, Causarano V, Dalfino L, Cassiano MA, Centonze A, Fabbri
L, Albano O.
Dept of Internal Medicine and Public Medicine, University of Bari,
Italy.
This observational study was designed to examine the pattern of sumatriptan use in patients with cluster headache using more than the recommended daily dose of subcutaneously injected (s.c.) sumatriptan. Thirteen patients suffering from episodic cluster headache were asked to record the characteristics of their attacks and drug intake for 1 year. All reported a high daily frequency of attacks (more than 3 per day) and the related overuse of s.c. sumatriptan. The results show that the overall incidence of adverse events among patients receiving sumatriptan injections for the treatment of cluster headache is low. The extended administration of this drug in episodic cluster headache did not result in tolerance problems or tachyphylaxis. Only 4 patients experienced minor adverse events and recovered more slowly than the others. They suffered from migraine without aura and cluster headache, and showed a family history of migraine. Even though they must be viewed with caution, due to the observational nature of the study and the low number of patients included, these results suggest that the profile of sumatriptan may differ in cluster headache compared with migraine.
PMID: 11062845
Daily Sumatriptan for Detoxification From Rebound
Peggy Drucker, Stewart Tepper, MD
Abstract
Medications which provide symptomatic relief from headache can
transform
episodic migraine into chronic daily headache by propagating the daily
headache,
causing "rebound." It is possible to restore the episodic migraine
pattern by using an inpatient course of intravenous dihydroergotamine.
This study was undertaken to explore whether it was possible to use oral sumatriptan in the outpatient setting as a bridge to detoxification for patients with chronic daily headache due to medication overuse. All patients had previously met International Headache Society (IHS) criteria for episodic migraine and currently had greater than 15 days of headache per month for greater than 1 month. These patients were advised to take 25 mg sumatriptan by mouth three times a day for 10 days or until they were headache-free for 24 hours.
Results reveal that of the 26 patients who started the protocol, 58% had reverted to an episodic migraine pattern at 1 month, and 69% were no longer having chronic daily headache at 6 months. This study demonstrates that it is possible to detoxify patients with rebound headaches using oral sumatriptan during the withdrawal period in an outpatient setting.
Key words: rebound, chronic daily headache, migraine, sumatriptan, dihydroergotamine, transformed migraine, withdrawal
Abbreviations: CDH chronic daily headache, DHE dihydroergotamine
People
with migraine are at risk for developing a second disorder, a pattern
of
chronic daily headache (CDH). Of those with CDH, over 80% have
converted to the
daily pattern and maintain it as a result of the medications taken to
relieve
headaches or symptoms.(1) The daily symptomatic relief medications can
transform
episodic migraine into CDH resulting in transformed migraine with
medication
overuse, or so-called "rebound."(2,3) It may take as few as 15
acetaminophen per week to cause this transformation.(4)
Rebound becomes an extremely frustrating situation for both clinician
and
patient. Once a patient is in rebound, prophylactic antimigraine
regimens are
far less successful in reducing headaches. It has been demonstrated
that there
is a change in membrane transduction during medication overuse, and
following
cessation, a return to baseline is seen, correlating with a reduction
in
headache frequency.(5) It is, therefore, imperative that the
rebound-causing
medications be withdrawn if the episodic migraine pattern is to be
restored.
However, because the patient has become habituated to the
rebound-causing
medications, detoxification from these medications may result in an
extremely
uncomfortable withdrawal period.
Currently, two conventional and widely used methods are employed to restore the episodic pattern of migraine. A patient may either choose to abruptly cease all rebound-causing medications, or undergo the inpatient approach to detoxification first described by Raskin. With the latter approach, intravenous dihydroergotamine (DHE) is used as a bridge to detoxification from the habituating drugs. Conventionally, patients are admitted to the hospital, symptomatic relief medications are withdrawn, and intravenous DHE and prophylactic antimigraine medications are employed to achieve this end.(6,7)
For some patients, a period in the hospital is not a viable option. This study was undertaken to see if repetitive oral sumatriptan, a conventional abortive antimigraine medication, given to patients with rebound headaches could be used as a bridge to detoxification during withdrawal of symptomatic relief medications in an outpatient setting.
METHODS
Patients meeting the proposed criteria of Silberstein et et al(3) for
transformed migraine with medication overuse were sequentially selected
from a
neurology practice. These patients all had greater than 15 days of
headache a
month and had previously had episodic migraine as classified by IHS
criteria.(8)
Exclusion criteria included evidence of cardiovascular or
cerebrovascular
disease, uncontrolled hypertension, hemiplegic or basilar migraine,
migraine
with prolonged aura, use of monoamine oxidase inhibitors, evidence of
rebound
caused by sumatriptan, habituation to more than two doses of
habituation per
day, and habituation to benzodiazepines.
After meeting the inclusion criteria, patients were instructed to discontinue the use of the rebound-causing medication(s) and begin taking 25 mg oral sumatriptan three times a day for 10 days or until they were headache-free for 24 hours. Concomitantly, the patients were started. on conventional prophylactic antimigraine medications tailored to their individual needs. Patients were asked to complete a headache diary for those days in which they had headaches. The day of the headache, as well as the severity (mild, moderate, or severe) and any medications taken, were recorded. Once the patient became headache-free for 24 hours or 10-days of daily sumatriptan use had elapsed, oral sumatriptan was then used to abort the moderate to severe headaches on an as needed basis. Follow-up at 2 weeks, 1 month, 3 months, and 6 months was obtained in order to ascertain the patients' headache status.
The primary endpoint of the study was whether the patient had converted back to an episodic migraine pattern at 1 month and at 6 months. Secondary endpoints included if this was achieved with sumatriptan alone (ie, whether they required additional DHE or other rescue medications) and, subjectively, whether the patient felt the sumatriptan was helpful during the detoxification period. In addition, it was noted if a patient was felt to have developed or begun to develop rebound headaches from the sumatriptan itself.
RESULTS
Thirty-five patients were sequentially selected to enroll in the study;
however,
9 left the clinic and did not begin the protocol The demographics of
tiffs group
are similar to that of those who followed through with the protocol.
The average
duration of CDH as reported by the 26 patients was 8.2 years.
The daily symptomatic relief medications used are shown in Table 1, and
the
prophylactic antimigraine medications used are shown in Table 2.
Of the 26 patients who began the protocol, 58% were no longer having
CDHs at 1
month and 69% had reverted to an episodic pattern at 6 months. Six
patients
required DHE or other rescue medications in addition to oral
sumatriptan during
the detoxification period.
Subjectively, only 2 patients did not feel that the sumatriptan was helpful during the withdrawal period, while 24 reportedly felt that sumatriptan did help relieve the withdrawal headaches during detoxification. Four patients were instructed to discontinue the use of sumatriptan following repetitive use after the 10-day detoxification period due to the possible development of rebound headaches from the sumatriptan.
COMMENTS
This was a nonblinded, nonrandomized study in which all patients were
placed on
the protocol, making it a suboptimal design. However, we were able to
demonstrate that it is possible to detoxify patients with transformed
migraine
from medication overuse using repetitive oral sumatriptan in an
outpatient
setting. While it took longer for patients to achieve headache freedom
using the
outpatient approach as compared to the DHE protocol, patients were able
to avoid
the time and costs associated with a hospitalization.
Importantly, the study included several patients who were habituated to ergotamine and who were successfully detoxified using this outpatient protocol. In the past, the standard of care for the ergotamine-habituated patient has been hospitalization.(9) Three of these patients were no longer having CDH at 1 month, and all four had returned to an episodic migraine pattern at 6 months. All four of the patients felt that sumatriptan was useful' during the withdrawal period. One of the ergotamine-habituated patients, however, was not able to use sumatriptan alone during the withdrawal period and did require three injections of DHE. However, it is important to note that this was all achieved as an outpatient. The next step would be to design a study with a larger number of ergot-habituated patients to further examine the use of repetitive triptans.
A concern at the onset of the study was the controversial and unresolved issue of sumatriptan rebound. The concern that one potentially rebound-causing medication was being substituted for another was raised. Several studies have demonstrated that daily sumatriptan use may cause rebound.(10,11) Four patients in the study were instructed to discontinue sumatriptan due to continued daily use beyond the 10-day withdrawal period. All but one of the patients did revert to an episodic migraine pattern following cessation of the sumatriptan. Because they were seen at such frequent intervals, it was felt that any patient in this study who had the potential to develop sumatriptan rebound from daily use beyond the 10-day withdrawal period would be screened and the possibility could be avoided. Further studies to determine whether or not sumatriptan is a potential rebound-causing medication, and the duration and dose required to cause this situation would be helpful in order to provide strict criteria for sumatriptan use. It may be possible to educate patients in the avoidance of sumatriptan-induced rebound.
Subjectively, all but two patients felt that sumatriptan provided a helpful bridge during the acute withdrawal period. Outpatient oral sumatriptan detoxification for medication-habituated patients may offer an alternative to the now traditional Raskin inpatient DHE protocol.
This study was designed using 25 mg sumatriptan by mouth three times a day, and it would be interesting to see if the time to headache freedom might be decreased by increasing the dose to 50 mg three times a day, since studies have shown that 50 mg is a more effective dose in aborting migraine.(12,13)
Further double-blind, randomized, placebo-controlled studies would be useful to examine whether outpatient repetitive oral sumatriptan is a viable alternative to detoxification. Additionally, with the introduction of the new selective 5-HT1 receptor agonists with varying pharmacokinetics, it would be interesting to study whether the longer-acting agonists would be beneficial in this setting.
Those with CDH and clinicians who treat them should, nonetheless, be optimistic about possible outpatient alternatives for management of CDH from medication overuse.
--------------------------------------------------------------------------------
REFERENCES
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3. Silberstein SD, Lipton RB, Sliwinski M. Classification of daily and
near-daily headaches: field trial of revised IHS criteria. Neurology.
1996;47:871-875.
4. Mathew NT, Kurman R, Perez F. Drug induced refractory
headache-clinical
features and management. Headache. 1990;30:634-638.
5. Hering R, Gardiner I, Catarci T, Whitmarsh T, Steiner T, de
Belleroche J.
Cellular adaptation in migraineurs with chronic daily headache.
Cephalalgia.
1993;13:261-266.
6. Raskin NH. Repetitive intravenous dihydroergotamine as therapy for
intractable migraine. Neurology. 1986;36:995-997.
7. Silberstein SD, Schulman EA, Hopkins MM. Repetitive intravenous DHE
in the
treatment of refractory headache. Headache. 1990;30:334-339.
8. Headache Classification Committee of the International Headache
Society.
Classification and diagnostic criteria for headache disorders, cranial
neuralgias and facial pain. Cephalalgia. 1988;8(suppl 7):1-96.
9. Raskin N. Headache. 2nd ed. New York: Churchill Livingstone; 1988.
10. Suchowersky O. Rebound headaches due to sumatriptan. Neurology.
1993;43(suppl 2).
11. Gobel H, Stolze H, Heinze A, Dworschak M. Easy therapeutical
management
of sumatriptan-induced daily headache.
Neurology. 1996;47:297-298.
12. Pfaffenrath V. A study comparing the efficacy, safety and
tolerability of
oral sumatriptan 25 mg, 50 mg and 100 mg doses in the acute treatment
of
migraine. Eur J Neurol. 1996;3(suppl 5):149.
13. Pfaffenrath V. Efficacy and safety of sumatriptan tablets (25 mg,
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oral sumatriptan. Cephalalgia. 1997;17:420.
After
Overuse, Type of Medication Determines Withdrawal Headache Symptoms
NEW YORK (Reuters Health) Dec 13 - The duration and severity of
withdrawal
headaches and accompanying autonomic symptoms following overuse of
headache
medication depend on the type of overused drug.
Dr. Volker Limmroth and colleagues from University Hospital Essen, Germany, conducted a prospective study of 95 patients to assess withdrawal headache following overuse of various headache medications, including single and combination analgesics, ergots, and triptans.
Patients who overused triptans had a significantly shorter duration of withdrawal headache (4.1 days) compared with patients who overused ergots (6.7 days) or analgesics (9.5 days; p < 0.002), according to the report in the November 13th issue of Neurology.
"By day 14 (last day of observation), 85% of the patients in the triptan group were headache-free, whereas only 57% of patients in the ergot group and 23% in the analgesic group reported themselves to be headache-free," the authors explain.
They observed no difference between the groups in terms of mean headache intensity on the first day of withdrawal (p = 0.821). However, by day 14, patients overusing triptans had lower mean headache intensity (0.08) than patients overusing ergots (0.4) or analgesics (0.9; p < 0.005).
"Because only patients with migraine, but no patient with tension-type headache, overused triptans, withdrawal headache was shorter in the group of patients with migraine alone (6.7 days versus 9.6 days for patients with tension-type headache and 8.5 days for patients with combination headache, p < 0.02)," Dr. Limmroth and colleagues note.
Headaches from Excessive Use of
Analgesics (Pain Pills) or
Ergotamine
Why they occur and what they are:
People who take analgesics frequently to alleviate migraines or
episodic
tension-type headaches risk developing a chronic daily headache. Most
patients
who develop such a headache have been taking daily doses of one or more
analgesics for at least several weeks to suppress their frequently
occurring
natural headache, and they continue doing so after the chronic daily
headache
sets in. Although this daily headache is not impressively reduced by
the
analgesic doses, it often flares up markedly when doses are delayed or
skipped.
Although excessive use of simple analgesics, such as acetaminophen, can
produce
chronic daily headache, compound analgesics, such as combinations of
aspirin,
caffeine, and butalbital, and opioids produce it more readily (see
example of
episodic tension-type headache changed to chronic daily headache by
Excedrin).
When such a headache develops from migraine, it is often referred to as
a
transformed migraine (see example). Ergotamine abuse is also well known
to
change intermittent migraines into a daily headache (example). The
intensifications of transformed migraine have prominent migrainous
features.
Many patients with chronic tension-type headache also take analgesics
daily.
Such use may worsen the headache and make it less responsive to
preventive
medicines.
Verifying
diagnosis of analgesic-abuse headache:
Although frequent use of analgesics or ergotamine strongly suggests
that a
chronic daily headache is from drug abuse, the diagnosis must be
verified by
seeing the headache lessen notably after a period (generally a month or
two) of
complete abstinence from the drug(s) in question. After such a period,
patients
with transformed migraines generally return to having intermittent
migraines,
and those whose daily headaches developed from episodic tension-type
headaches
generally experience the latter type once again. Those whose original
headaches
were the chronic tension-type continue to have a chronic daily
headache, but it
generally lessens in severity and shows a responsiveness to standard
preventives
not present during heavy analgesic use.
Diagnostic
criteria of the International Headache Society:
These are omitted here because they are (frankly) outdated. Recently
published
criteria for transformed migraine better reflect current thinking about
the
degree of analgesic or ergotamine use leading to its development
(Silberstein et
al., 1994). These criteria (not validated) state that migraine can be
transformed into chronic daily headache with any of the following
abuses for at
least one month:
Simple
analgesic use: over 1000 mg of aspirin or acetaminophen, or an
equivalent of another drug, more than 5 days per week.
Compound analgesic use: over 3 tablets per day more than 3 days per
week.
Opioid use: over 1 tablet per day more than 2 days per week.
Ergotamine use: 1 mg more than 2 days per week (rebound headache from
excessive
use of ergotamine was recognized long before analgesic-abuse headache
was
identified).
Comment: Similar analgesic use can change episodic tension-type
headache into
chronic daily headache or worsen chronic tension-type headache.
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