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Current Understanding and Management Of Medication-overuse Headache

While the number of patients presenting with medication-overuse headache is growing, the condition is commonly overlooked and difficult to treat.
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Medication-overuse headache (MOH) is a chronic disorder that arises from the frequent use of acute (abortive) medications for the treatment of a primary headache. It manifests as almost daily headaches that cause substantial disability and diminish health-related quality of life.

The International Headache Society defines MOH as a condition in which headaches occur on 15 or more days per month when the therapeutic agent is used excessively and on a regular basis for three or more months and when headaches have developed or worsened during the period of medication overuse.1

MOH has become a chronic headache of growing worldwide importance. The World Health Organization Atlas of Headache Disorders reported that in primary and neurology care, a respective 6% and 9% of headache sufferers present with this disorder. In specialized headache clinics the figure is closer to 30%, and more than 50% in the United States.2 Data from a physician survey that included neurologists, headache specialists, and general practitioners suggested that MOH may be the third most frequent type of headache after migraine and tension type headaches (TTHs).3 Yet, while the number of patients presenting with this condition is growing, MOH is commonly overlooked and difficult to treat.4 This review aims to discuss the clinical features, risk factors, and pathophysiology of MOH. It also summarizes current strategies for managing and preventing headache chronicity.

Clinical Features
The primary headache disorders leading to MOH include migraine headache (65%), TTH (27%), or a combination of the two (8%). Interestingly, individuals with cluster headaches generally consume acute medication without developing MOH. Women are more prone to MOH than men. Studies indicate that the average duration of the primary headache is 20.4 years, the mean duration of the excessive medication intake is 10.3 years, and the mean period of daily headaches is 5.9 years in patients with MOH.5

In principle, all acute-care headache medications have the potential to cause MOH. These include over-the-counter drugs like aspirin and acetaminophen, combination medications containing paracetamol and aspirin, non-steroidal anti-inflammatory drugs, anti-migraine abortive drugs (ergots, triptans), barbiturate-containing medications (mainly butalbital), opioids, and opioid agonist/antagonist agents (butorphanol). However, triptans in particular are currently the most frequently overused medication associated with MOH.6

The time until development of MOH and the amount of drug that is sufficient to trigger MOH varies with the individual agent. One prospective study of 96 headache patients who developed MOH revealed that the delay between starting the drug and developing MOH was shortest for triptans (1.7 years), longer for ergots (2.7 years), and longest for analgesics (4.8 years). It was further demonstrated that just 18 single doses of triptans per month were enough to induce MOH, compared with the lowest doses per month of 37 and 114 for ergots and analgesics, respectively.4 Generally, for an episodic condition to transform into a chronic one, medications need to be taken only a modest number of days per month: five to 10, depending on the type of drug.7

Since up to 90% of all patients with MOH consume more than one specific drug for the treatment of acute attacks, it is difficult to differentiate exactly between the features of different MOH subtypes according to the drug overused. Nevertheless, recent studies reveal that patients who intake ergotamine and analgesics tend to develop a daily TTH-like headache, whereas patients with triptan-induced MOH are more likely to report a migraine-like headache or an increase in migraine frequency.6

Irrespective of the offending agent, there are several general clinical characteristics that can help distinguish MOH in patients with primary headache disorders (Table 1). The threshold for head pain is low, with the slightest physical and intellectual exertion being enough to trigger headache. It has been found that simultaneous prophylactic drugs are unsuccessful while the patient is taking excess amounts of the culprit drug. Moreover, withdrawal symptoms are observed when patients are taken off their pain medications abruptly. However, spontaneous improvement of the headache does occur within days of drug discontinuation.4

The mechanisms that underlie MOH remain unclear, primarily due to a lack of experimental work and appropriate animal models. Several mechanisms are theorized to play a key role.

Genetic Disposition
Since only patients suffering from migraine or TTH, but not patients with cluster headache, are seen to develop MOH upon chronic analgesic overuse, genetic determination appears to be important. This is supported by the observation that patients with other chronic painful disorders, such as rheumatoid arthritis, take large amounts of analgesics regularly without incidence of increased headache. On the other hand, patients with migraine who consume analgesics for non-headache pain (ie, neck pain) are significantly more prone to develop MOH than those without migraine. The conclusion drawn from this evidence suggests a specific genetic susceptibility for patients with migraine or TTH to develop MOH.8

Altered Receptor and Enzyme Physiology
It has also been postulated that headache medications have a direct inhibitory effect on the pain-regulating capacity of our brain. Repetitive exposure to triptans causes a substantial decrease in serotonin synthesis and downregulation of serotonin receptors in various cortical regions, the extrapyramidal system, and the brainstem. These alterations may occur as soon as 24 to 96 hours after chronic exposure. Similarly, analgesics like aspirin decrease functional cyclooxygenase (COX)-1 and 2 function. This reduction of serotonin receptors and prostaglandin-synthesizing enzymes occurs in brain structures that transmit or modulate nociceptive signals. For example, the periaqueductal gray matter functionally loses serotoninergic pathways that inhibit trigeminal nuclei. The result is impaired antinociceptive activity and the creation of a hyperalgesic state.4

Last updated on: September 25, 2012
First published on: June 1, 2012