CHRONIC DAILY HEADACHES

Medication Overuse Headache

By Stuart B Black , M.D.; FAAN

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 and Frova ).⁴ In summary, Medication Overuse Headache can be facilitated by virtually any agent used for symptomatic relief of headache. Headache associated with drug overuse is one of the most common reasons for consultation at The Dallas Headache Association and is one of the most 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 can 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 interferes with the therapeutic benefit of standard usually effective pharmacological (example: prophylactic headache medications) and nonpharmacological treatment regimens, thus preventing expected improvement. A patient who has Medication Overuse Headaches will often not respond to other commonly used treatment protocols. The other often effective headache medications may be ineffective until discontinuance and withdrawal of the daily or almost daily pain medication is accomplished. Therefore, preventive medications such as Topamax, Depakote, Neurontin, Inderal, Atenelol, Amitriptyline, Verapamil, etc. may have been tried without benefit. Discontinuation of the offending pain medication or medications 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 actually causes important changes in 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 affects 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 are also biochemical changes which take place within the brain tissue. Research has shown that important substances such as serotonin, glutamate, calcitonin gene related peptide (CGRP), nitric oxide, etc. play an important role in the mechanism of migraine and are also important in the pathophysiology of Medication Overuse Headache. These substances are important neurotransmitters in brain metabolism 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 and modulatory systems within the brain. Derangement of these modulatory systems secondary to chronic use of analgesics may underlie the development of chronic headache and may play a role in the development of Medication Overuse 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 There is tissue damage or damage to the neurons (brain cells). These changes appear to represent a permanent injury to specific 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 refractive headaches). It is also possible that the frequent use of pain medications may also play a role in this process. There is evidence to suggest that eventually these events which 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. This may represent a population of patients who do not respond to medication withdrawal (detoxification), and who continue to have chronic refractive headaches even when off pain medication. Fortunately, this population of refractive headache patients represents a 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. There is literature which indicates that it may take up to 2‑6 months "for the brain to heal" following withdrawal of pain medication. In those who persist in having daily headaches even when off frequent pain medication, one possible explanation points to the irreversible central nervous system (brain) damage.

If one were to summarize the new 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 the IHS criteria defines improvement at a 2 month period following discontinuation of overused medication, as indicated above, there are many headache specialists who support additional published data that, indeed, 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 not entirely scientifically defined, the etiology is felt to be a 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 the offending analgesics. Clinical experience indicates that medical and behavioral headache treatment fails 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 drug-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. Other patients may require psychotherapy and appropriate medical management of associated neuropsychiatric conditions. Treatment may 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 possible.

In any medication withdrawal process, potential withdrawal symptoms including severe headache exacerbation, nausea and vomiting, agitation, restlessness, sleep disturbance, and even more significant neurological and medical issues must be anticipated and treated if present. Depending on the pain medications used, other withdrawal symptoms may include arterial hypotension, tachycardia (rapid heart rate), and, although only rarely observed, in patients who overuse barbiturate‑containing headache drugs, seizures and hallucinations could occur. Although typical withdrawal symptoms often last for 2 to 10 days, in others, symptoms may persist for 2 weeks or longer. 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 or medication withdraw symptoms 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 my also be complicated by psychological factors which include the reinforcement that pain relief may occur by drug consumption. From a psychiatric standpoint, this may be referred to as a form of positive conditioning. Therefore, a transition or bridging regimen may be necessary. The transitional medications might include alternative analgesics and nonpharmacologic support that increases the patient's ability to work through the withdrawal process. The use of "rescue medications" is also often useful during the washout 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 and may cause sedation as a side effect. The above considerations are usually designed for an outpatient treatment protocol recognizing that the patient would have to be a reliable individual who is motivated and able to proceed according to physician instructions. However, in those patients who have not responded or are refractive to outpatient treatment, hospitalization for inpatient care is appropriate.

Hospitalization must also be considered if it is anticipated that an outpatient environment for "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 more than 5 years 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. As an example, repetitive intravenous Dihydroergotamine (DHE), which is one of the more commonly used intravenous medications for the treatment of migraine and refractory chronic headaches, when used >2 days has been recognized by the American Academy of Neurology in their practice parameter as necessitating inpatient monitoring.¹² There are published criteria for admission to headache inpatient treatment centers.^13,14 The following is an example of hospital admission criteria used at the Dallas Headache Association for headache patients:

• Failed outpatient detoxification

• The need for in patient (hospital) detoxification

• Need to treat dependency or Medication Overuse phenomena

• Dependence on pain medication, ergots, opiates, barbiturates, or            tranquilizers

• Presence of moderate to severe acute intractable headache that fails to respond to appropriate outpatient care and requires sustained and intravenous medications such as DHE

• Presence of continuing nausea, vomiting, or diarrhea

• Presence of dehydration, electrolyte imbalance, and prostration that requires intravenous fluids

• Monitor protectively against withdrawal symptoms

• Monitor medical and neurological signs during withdrawal

• Presence of unstable vital signs

• Presence of repeated previous emergency department visits for headache care

• Need to rapidly develop both immediate pain reduction and effective pharmacologic prophylaxis

• Need for daily monitoring of intravenous medications and frequent adjustments of medications

• Need to urgently address other medical conditions contributing to or accompanying the headache, including psychological factors

• Presence of pain that is accompanied by serious adverse reactions such as complications from therapy or when continued use of such therapy could induce further illness

• Treatment requiring copharmacy with drugs that may cause a drug interaction thus necessitating careful observation

• Diagnostic suspicion of a serious medical condition or disease

It should be emphasized that patients with Medication Overuse Headaches must accept the realization that often 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 chronic pain, the pathophysiological, biochemical and behavioral mechanisms may lead to a "chronification" process which may be further complicated by the overuse of pain medication. In addition, Medication Overuse Headache is considered by many to be a major health problem made even worse by the potential secondary effects of chronic medication overuse. Acute pain medications when overused may affect other organ systems which could result in chronic kidney failure (combination analgesics), gastrointestinal ulcers (nonsteroidal anti‑inflammatory drugs), or even have potential harmful effects on the cardiovascular system (vasoactive drugs such as the ergots 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 intravenous intervention should not be considered as "the cure”. If inpatient treatment is necessary it should be based upon a defined criteria (example given above) or other important factors specific for an individual patient. Whereas in patient hospital care offers a patient the opportunity to minimize the side effects of withdrawal from analgesics as well as receive the benefits from commonly used intravenous medications, the central nervous system changes that may result from medication overuse must have an opportunity to improve. 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 during which time "the brain must heal", and during which time psychological and behavioral factors must 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.

Additional Patient References

Example of Treatment Options

Example Of Hospital Treatment Plan