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Chronic Daily Headaches 

Medication Overuse Headache

The following brief review is written specifically for those patients who have chronic headache resulting in the frequent use of pain medication.

Studies show that approximately 4% of the American population suffers from headache more than 15 days per month. 1 Most of those individuals have a daily or almost daily headache syndrome. Further reports indicate that as many as 80% of those patients with chronic daily headache may use pain medication on a daily or almost daily basis. 2

Although previous terms such as analgesic rebound headache, drug induced headache, and transformed migraine have previously been used to describe headache associated with sustained drug exposure, the recently revised International Headache Society Classification Criteria has classified these headaches under the term Medication Overuse Headache (MOH).3 

Under the International Headache Society guidelines, MOH is headache that occurs >15 days per month, is associated with the frequent intake of pain medications, and resolves after discontinuation of the medication. The clinical syndrome becomes a self sustaining, rhythmic, headache medication cycle characterized by the daily or almost daily headache in association with the daily or almost daily use of analgesics. MOH can occur as a result of the overuse of simple over the counter pain medications (Aspirin, Excedrin, Advil, Aleve, Tylenol, BC Powders, etc.) and / or as a result of prescription pain medications ( Fiorinal and other Butalbitals, Darvon, Ultram, Stadol Nasal Spray, etc.) including narcotics (Vicodin and other Hydrocodones, Codeine, Demerol, etc.) and triptans (Imitrex, Zomig, Maxalt, Relpax, Axert, Amerge Frova and Treximet ).4

In summary, Medication Overuse Headache can be facilitated by virtually any agent used for symptomatic relief of headache. Headache associated with medication overuse is one of the more common causes of Chronic Daily Headache in patients who present to specialized headache clinics in North America.5,6

As the science of Medication Overuse Headache has become better understood, it also became recognized that medication overuse may make headaches refractory to preventive (prophylactic) therapy.7 This means that not only will analgesic overuse in headache patients lead to worsening of headache rather than relief, but that pain medication consumption also appears to interfere with the therapeutic benefit of standard usually effective pharmacological (example: prophylactic or preventive headache medications) and nonpharmacological treatment regimens, thus preventing expected improvement. It is widely accepted that a patient who has Medication Overuse Headaches will often not respond to other commonly used treatment protocols. There is evidence to suggest that other potentially effective headache medications may be ineffective until discontinuance and withdrawal of the daily or almost daily pain medication is accomplished. Therefore, medications such as Topamax, Depakote, Atenelol, Toprol, Amitriptyline, Verapamil, and other commonly used prophylactic medications, may have been tried without benefit. Based on the literature, in most instances, it is strongly recommended that the discontinuation of daily or almost daily pain medication is critical to establishing effective headache management.

The earlier terminology of Analgesic Rebound Headache which historically had been widely used to describe Medication Overuse Headache implies that the headache was caused by withdrawal from analgesics. However, the term "rebound" was originally intended to explain the increased headache frequency observed with medication overuse. Thus, the overuse of pain medication may actually result in important changes within the brain which perpetuate the recurrent headache. One might infer that the medication used to prevent today's headache actually causes tomorrow's headache.

The syndrome of headaches caused by medication overuse is not a drug withdrawal. The condition is not indicative of drug addiction. Instead, Medication Overuse Headache is a condition which appears to affect different parts of the Central Nervous System (CNS). These CNS changes may directly suppress certain pain receptors within the brain and may actually down regulate or even diminish the number of anti‑pain receptors in the brain. There may also be biochemical changes which take place within the brain tissue. Research has shown that important substances within the brain such as serotonin, glutamate, calcitonin gene related peptide (CGRP), nitric oxide, and others, play an important role in the mechanism of migraine and therefore, would likely be involved in Medication Overuse Headache. These substances are known as neurotransmitters and may be instrumental in the production of increased pain when analgesics are stopped. Headaches such as migraine appear to develop through a cascade of events that take place within the brain during a migraine attack. An alteration of these events secondary to chronic use of analgesics may underlie the development of chronic headache.

Research has also shown that there are anatomical or physical changes that also occur in the brain as a result of frequent migraine.8 In specific areas of the brain, there appears to be tissue damage or damage to the neurons (brain cells). These changes take place in areas of the brain that are involved in the pain modulating system. One possible implication is that untreated chronic migraine leads to further injury and dysfunction of the brain's antinociceptive (anti‑pain) system. Theoretically, this impairment of the antinociceptive (anti‑pain) activity could subsequently result in a permanent feeling of head pain (chronic headaches). It is also possible that the frequent use of pain medications may also play a role in this process. 

There is concern that eventually these events which may lead to permanent central nervous system changes result in chronic daily headaches. Clinical experience has also shown that, in a specific group of individuals, even stopping the daily or almost daily pain medication does not disrupt the chronic daily headache pattern. Therefore there may be a population of patients who do not respond to medication withdrawal (detoxification), and who continue to have chronic refractory headaches even when off pain medication. Fortunately, this population of refractory headache patients represents a relatively smaller group of individuals with MOH. The majority of patients with Medication Overuse Headaches, if motivated, have a favorable prognosis for recovery. However, the rehabilitative process takes time. The experience of many Headache Medicine specialists suggests that it may take several months following withdrawal of pain medication before headache improvement is appreciated. In those who persist in having daily headaches even when off frequent pain medication, one possible explanation points to pathophysiological changes within the brain itself.

If one were to summarize the International Headache Society (IHS) criteria for Medication Overuse Headache, the diagnostic criteria would include:9

A. Headache present on >15 days/month.

B. Regular use of a medication > 3 months of one or more acute / symptomatic treatment drugs:

1. Ergotamine, triptans, opioids, or combination analgesic medications >10 days a month on a regular basis for >than 3 months.

2. Simple analgesics or any combination of ergotamine, triptans, analgesic opioids >15 days/month on a regular basis for >3 months without overuse of any single class alone.

C. Headache has developed or markedly worsened during medication overuse.

It should be emphasized that although improvement may occur even within a 2 month period following discontinuation of pain medication, there are many headache specialists who agree that it may take up to 6 months (or even longer) for a patient to reach maximum improvement.10

Therefore, although the exact cause of Medication Overuse Headache is still within the research phase, the etiology points to a probable complex interaction of biochemical, anatomical, environmental and psychological factors. Consideration of all these issues is important in developing an effective treatment plan. It has been universally agreed, that after the proper diagnosis has been established, effective therapy requires withdrawing from the daily use of pain medication. Clinical experience indicates that medical and behavioral headache treatment has less chance of being successful as long as the patient continues to take daily or almost daily pain medications. 

The withdrawal of analgesics is frequently difficult and depending on the degree of involvement, must be accomplished under appropriate medical supervision. Patients suffering from medication-induced headache may also exhibit primary or secondary emotional disorders such as depression, low frustration or low tolerance due to the chronic pain. Other patients may exhibit physical and emotional dependency. Some patients may benefit from treatment with behavioral methods including biofeedback, stress management, and cognitive behavioral therapy.

There are those in whom psychotherapy and appropriate medical management of associated neuropsychiatric conditions is very helpful. In addition, treatment should also include lifestyle changes, cessation of smoking, a healthy diet, regular eating and sleeping patterns and an exercise program. Headache triggers must be avoided if recognized.

In any medication withdrawal process, potential withdrawal symptoms including severe headache exacerbation, nausea and vomiting, agitation, restlessness and sleep disturbance may occur. Depending on the medication the patient is overusing, there may be other neurological and medical issues that should be anticipated and treated if present. Although only rarely observed, in patients who overuse barbiturate containing headache drugs, one must caution against the possibility of seizures and hallucinations. If only minor withdrawal symptoms were to occur, they often last on an average of 2 to 10 days. It is likely that almost every headache specialist has encountered patients who have attempted, on their own, to discontinue pain medication and have experienced such escalation of pain that they are reluctant to stop their medications. Other patients simply have a great deal of trepidation about stopping their medications. The discontinuation of pain medication may also be complicated by psychological factors which include medication dependency. Therefore, a transition or bridging regimen is usually recommended. The transitional medications might include alternative analgesics and nonpharmacological support that increases the patient's ability to work through a potential withdrawal process. The use of "rescue medications" is sometimes useful during the discontinuation phase of treatment when daily or almost daily analgesics are being withdrawn. It is important that the patient understand that a rescue medication is not appropriate for frequent use. The above considerations are usually designed for an outpatient treatment protocol recognizing that the patient would need to be a reliable individual who is motivated and able to proceed according to physician instructions. Family support and/or support from other relationships is also important. However, in those patients who are not candidates and/or have not responded to outpatient treatment, hospitalization for inpatient care is appropriate.

Hospitalization must also be considered if it is anticipated that an outpatient environment for withdraw or "detoxification", (the term used for withdrawal from pain medications), will not be successful or safe. Other factors that must be considered include the medical stability of the patient, presence of coexisting medical illnesses, drug dependency issues, associated psychological and psychiatric conditions, and the need for patient monitoring during intravenous administration of medical therapies. In addition, there are those who believe that a short hospital stay is recommended if Medication Overuse Headaches have lasted a longer period of time and the patient has required the use of tranquilizers, barbiturates, and/ or narcotics. 

The US Headache Guidelines Consortium, Section on Inpatient Treatment recently published an excellent comprehensive review entitled Inpatient Treatment of Headache: An Evidenced Based Assessment.11 The report, which was conducted by leading headache experts, evaluated the hospital treatment of headache patients within the United States. Although there remain a number of areas for further research to add to the current information that is available, the following is the Consensus Statement from that review: 

"There is a need for inpatient headache treatment, and appropriately selected patients benefit over both the short and long term. Overall, the results indicate very positive improvements in patients following discharge from inpatient care in centers both here and abroad, with outcomes generally maintained over follow‑up periods from 2 weeks to 5 years."

It is well recognized that there are a number of headache patients with frequent intractable headaches, often associated with significant disability, who do not benefit from traditional outpatient care. Many of these individuals could benefit from more intense levels of care, including inpatient treatment. It may also be necessary to hospitalize a patient during periods of severe acute headache which has not responded to the usual abortive or rescue medications, or when severe headache is associated with significant changes in vital signs and other clinical conditions, such as repetitive vomiting.  

The use of intravenous medications requires supervised monitoring; whether administered in an outpatient infusion center or in the hospital. As an example, repetitive intravenous Dihydroergotamine (DHE) is one of the more commonly used intravenous medications for the treatment of migraine. Some headache centers, if indicated, administer intravenous DHE in an infusion center monitored by nurses trained in intravenous infusions. If however, a patient does not respond after two days of outpatient treatment, admission to the hospital is usually indicated. The American Academy of Neurology in their practice parameter has set out guidelines for inpatient hospital monitoring.12 There are also published criteria for admission to headache inpatient treatment centers.13, 14  

The following is an example of the type of patients who would be considered candidates for hospitalization.

  • Failed outpatient withdrawal from pain medications
  • The need for in patient hospital service
  • The need to treat medication dependency
  • Patients who overuse ergots, opiates, barbiturates, or tranquilizers
  • The presence of severe acute intractable headache that fails to respond to appropriate outpatient care
  • Those patients who require sustained use of intravenous medications such as DHE
  • The presence of continued nausea, vomiting, or diarrhea
  • The presence of dehydration, electrolyte imbalance, and prostration that requires intravenous fluids
  • Those patients who require protective monitoring against withdrawal symptoms
  • Those patients who require monitoring of medical and neurological signs during withdrawal
  • The presence of unstable vital signs
  • The presence of repeated previous emergency department visits for headache care
  • The need to rapidly initiate both immediate pain reduction and effective pharmacologic prophylaxis
  • The need for daily monitoring of intravenous medications and frequent adjustments of medications
  • The need to urgently address other medical conditions contributing to or accompanying the headache
  • The need to urgently address a patient’s psychological factors
  • The presence of pain that is accompanied by serious adverse reactions such as complications from therapy
  • The need to observe the patient for potential interactions between different medications
  • The need for evaluation of other suspicious serious medical conditions or diseases 

It should be emphasized that patients with Medication Overuse Headaches must accept the realization that several mechanisms appear to play an important role in the production of chronic daily or almost chronic daily headaches. In addition to the disability associated with persistent pain, the pathophysiological, biochemical and behavioral mechanisms may lead to chronic changes within the brain. In addition, Medication Overuse Headache is considered by many to be a major health problem. Acute pain medications when overused could also affect other organ systems. Overuse of various medications may result in chronic kidney failure and gastrointestinal ulcers (nonsteroidal anti‑inflammatory drugs, combination pain medications), or even have potential harmful effects on the cardiovascular system (drugs that constrict the arteries such as the ergotamines and possibly even the triptans) if used daily or almost daily.  

It is also important for patients with Medication Overuse Headaches to recognize that even hospitalization and the use of intravenous medications should not be considered as "the cure”. If outpatient treatment fails and inpatient hospital treatment is necessary, admission should be based upon defined criteria; as indicated in the above examples. Whereas in patient hospital care may offer a patient the opportunity to minimize the side effects of withdrawal from analgesics as well as receive the benefits from commonly used intravenous medications, improvement from headache pain still must occur over the course of time.  

The prognosis for a good functional recovery also depends on each patient's individual clinical situation. In other words, "There Is No Quick Fix".

There is a period of rehabilitation for every patient during which time any psychological and behavioral factors must also be addressed. The overall treatment of Medication Overuse Headache should be considered a rehabilitative model of care which is important to maximize the functional capacity, and quality of life potential of the chronic headache patient. 

Stuart B Black M.D.; FAAN

Chief of Neurology at Baylor University Medical Center at Dallas

Co Director of the Baylor Neuroscience Center

REFERENCES

1. Scher AL Lipton RB, Stewart W. Risk factors for chronic daily headache. Curr Pain Headache Rep. 2002;6:486‑491.

2. Mathew NT. Transformed migraine. Cephalgia. 1993; 13(suppl 12):78‑83.

3. Headache Classification Subcommittee of the International Headache Society. The international classification of headache disorders: 2nd edition. Cephalalgia 2004; 24 (suppl 1): 1‑60.

4. Limmroth V, Katsarava Z, Fritsche G, Przywara S, Diener HC. Features of medication overuse headache following overuse of different acute headache drugs. Neurology 2002; 59 (7): 1011-1014.

5. Mathew NT, Reuveni U, Perez F. Transformed or evolutive migraine. Headache 1987 ; 27: 102‑106.

6. Rapoport AM,. Analgesic rebound headache. Headache 1988 28: 662‑665.

7. Mathew NT,, Kkurman R,‑ Perez F. Drug induced refractory headache clinical features and management. Headache 1990; 30: 634‑638.

8. Welch KM, Nagesh V, Aurora SS, Gelman N. Periaqueductal gray matter dysfunction in migraine: cause or the burden of illness? Headache 2001; 41: 629‑637.

9. Headache Classification Committee: Cephalalgia 2006; 26: 742-746.

10. Headache Classification Subcommittee of the International Headache Society. The international classification of headache disorders. Cephalalgia 2004; 24: 94‑95.

11. Freitag FG, Lake AL, Lipton R, Cady R. Inpatient Treatment of Headache: An Evidenced Based Assessment. Headache 2004: 44: 342‑360.

12. American Academy of Neurology. Practice parameter: appropriate use of ergotarnine tartrate and Dihydroergotamine in the treatment of migraine and status migrainosus (summary statement). Report of the Quality Standard Subcommittee of the American Academy of Neurology. Neurology. 1995: 45: 585‑587.

13. Saper JR, Silberstein S, Gordon CD, Hamel RL,, Swidan S. Handbook of Headache Management. A Practical Guide To Diagnosis of Head, Neck, and Facial Pain. 2nd ed. Philadelphia: Lippincott, Williams and Wilkins; 1999.

14. Fritag F, Cady R, eds. The National Headache Foundation Standards of Care. 3rd ed. National Headache Foundation, 2001.