Other diagnoses entertained. The more diagnoses suggested for daily headache, and the more treatments tried unsuccessfully, the more likely the diagnosis is actually medication overuse headache. Because this condition is protean, patients and caregivers alike make more and more fanciful diagnoses such as allergies, cervicogenic headache, temperomandibular disorder, occipital neuralgia, chronic Lyme disease, and systemic candidiasis. A useful strategy is to assume that daily headache is likely due to medication overuse. And since medication overuse headache is generally treatable, patients labeled as having refractory headaches often are dramatically improved by appropriate intervention.
WHY ARE MIGRAINEURS SO SUSCEPTIBLE?
Medication overuse headache occurs primarily in people with a history of episodic migraine, but the unique susceptibility of migraineurs is not fully understood.
Structural changes in the brain?
Episodic migraine attacks appear to be generated in the upper brainstem. This region in turn activates a set of peripheral pain mechanisms, ie, meningeal inflammation and vasodilation. The peripheral pain processes turn on afferent circuits that carry the pain signals to the lower brainstem, where these signals are integrated. Finally, the central signals ascend the brainstem, stimulating autonomic nuclei that account for nausea and other vasomotor changes, proceed through the thalamus, and terminate in the cortex where pain is perceived. Thus, migraine without aura consists of three steps—a central generator, a set of peripheral pain mechanisms, and a series of steps culminating in central integration. (Aura involves other steps, not outlined here.)
A possible explanation of why migraine becomes chronic is that a yo-yo effect of repeated migrainous pain processes, followed by repeated medication, results in structural changes. These propagate central sensitization with a lowered threshold for activation of all of the central processing of head pain.
This set of disturbances may occur due to undertreatment of migraine pain. With inadequate pain control, headaches recur, and the process repeats until damage occurs. Evidence for this is seen in up-regulation of excitatory serotonin receptors when analgesics are repetitively given to laboratory animals. 23
A pure withdrawal phenomenon?
Also possible is that medication overuse headache is just a complex dependence-and-withdrawal phenomenon. Thus, the cyclical use of various medications results in withdrawal headaches and a set of symptoms, including disturbed sleep, morning headache, and vasomotor signs of withdrawal. Arguing against its being a pure withdrawal phenomenon is that daily use of analgesics or opioids generally does not cause daily headache in nonmigraineurs. 24
HOW MUCH MEDICATION USE IS TOO MUCH?
For an episodic migraine condition to transform into a chronic one, medications need to be taken on only a modest number of days per month: 5 to 10, depending on the type of medication.
A pivotal study 3 found that butalbital combinations were most likely to cause medication overuse headache, needing to be taken on merely 5 or more days per month to cause it in migraineurs. Opioids caused it if taken 8 or more days per month, and triptans if taken 10 or more days per month. Nonsteroidal anti-inflammatory drugs (NSAIDs) actually protected against transformation to daily headache if used 5 or fewer days per month, but caused medication overuse headache if used 10 or more days per month.