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 up to 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% pf those patients with chronic daily or almost daily headaches 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 been previously used to describe headache associated with sustained medication exposure, the 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 the discontinuation of the medication.  The clinical syndrome of MOH 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, Percodan, Percocet, etc.) and triptans (Imitrex, Zomig, Maxalt, Relpax, Axert, Amerge, Frova, Treximet, etc.).4   In summary, Medication Overuse Headache can be facilitated by virtually any agent used for symptomatic relief of headache.  Headache associated with the 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 the headache rather than relief, but that pain medication overuse also appears to interfere with the therapeutic benefit of standard usually effective pharmacological and nonpharmacological treatment regimens, specifically prophylactic or preventive headache medications.  Thus, the use of preventive medications does not result in the expected improvement until discontinuance and withdrawal of the daily or almost daily analgesics are accomplished. 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 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

 

1. Headache present on >15 days/month.
2. Regular use of a medication > 3 months of one or more acute / symptomatic treatment drugs:
3. Ergotamine, triptans, opioids, or combination analgesic medications >10 days a month on a regular basis for >than 3 months.
4. 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.
5. 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

 

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 such as Butalbital, one must caution against the possibility of seizures and hallucinations. If most patients, with appropriate medical supervision, if 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 safer analgesic control and nonpharmacological support that increases the patient’s ability to work through a potential withdrawal process. The use of “rescue medications” is sometimes necessary 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.

In fully Comprehensive Multidisciplinary Headache Centers the above considerations and treatment models are designed for outpatient treatment protocols which may include the availability of eadache medicine outpatient infusion centers for the administration of appropriate specific intravenous medications when indicated.  Family support and support from other relationships is also important.   In those few patients who have additional medical comorbidities that may also require treatment, hospitalization for inpatient care may also be appropriate.  Although very few in number, those select headache medicine patients who may require hospitalization, earlier medical literature has defined the efficacy of hospitalization in that patient population. The most frequently quoted reference is from the US Headache Guidelines Consortium, Section on Inpatient Treatment. That excellent comprehensive review was entitled “Inpatient Treatment of Headache: An Evidenced-Based Assessment”11 But again, it is to be emphasized that only a small minority of patients require hospitalization for the effective treatment of Medication Overuse Headaches.

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 or even have potential harmful effects on the cardiovascular system if used daily or almost daily.

 

With appropriate treatment under the supervision of a headache medicine specialist, 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 with objectives and goals to improve the patient’s quality of life and maximize their functional capacity, while protecting them from the potential long term undesirable side effects following the chronic use of analgesics for headache control.

 

SBB

 

   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.