Breaking the cycle of medication overuse headache
ABSTRACTWhen patients who have frequent, disabling migraines take medications to relieve their symptoms, they run the risk that the attacks will increase in frequency to daily or near-daily as a rebound effect comes into play. This pattern, called medication overuse headache, is more likely to happen with butalbital and opioids than with migraine-specific drugs, as partial responses lead to recurrence, repeat dosing, and, eventually, overuse. Breaking the cycle involves weaning the patient from the overused medications, setting up a preventive regimen, and setting strict limits on the use of medications to relieve acute symptoms.
KEY POINTS
- Medication overuse headache can occur with as few as 5 days per month of treatment with butalbital or 8 days per month with opioids.
- The features vary, but the most important is headache on 15 or more days per month, lasting at least 4 hours if untreated, for at least 3 consecutive months. Other common symptoms are morning headaches, neck pain, nonrestorative sleep, and vasomotor instability, all of which tend to improve with weaning from the overused medications.
- Daily preventive treatment is indicated when patients have 10 or more headaches per month or severe disability from their attacks.
- With treatment, the prognosis for medication overuse headache is good. However, patients need close followup to prevent recidivism.
SYMPTOMS VARY
The symptoms of medication overuse headache vary in frequency, severity, location, quality, and associated features, both among patients and in the same patient. This is because the disease itself varies and also because of differences in the type and frequency of medication intake. Still, some features help to define this problem, and failing to recognize them may account for a widely held clinical feeling that these patients are “difficult.”
History of episodic migraine. Generally, medication overuse headache does not occur in nonmigraineurs.
Headache on most days of the month. Whenever a migraineur starts having headaches on more days than not, the diagnosis of medication overuse should be considered.
Overuse of acute medications. The criteria (see above) allow for combining days of acute medication use. For example, if a patient takes a combination analgesic on 5 days and a triptan on 5 different days, that would still be enough days of acute treatment to trigger medication overuse headache.
Variable pain location is a particular characteristic of medication overuse headache. Although the location may differ from day to day (front or back, rostral or caudal, unilateral or bilateral), it is the quantity not the quality or location of the headaches that suggests the diagnosis.
A drug-dependent rhythm. Predictably, the headaches come on in the early morning or awaken the patient from sleep. This may be due to variable drug withdrawal.
Neck pain. Medication overuse headache frequently involves the neck, and patients often seek and receive treatments such as muscle relaxants or injections to the neck. When patients are weaned from their acute migraine medications, neck pain generally dissipates. The neck pain, however, can recur episodically with their remaining, now-episodic acute migraines. Neck pain associated with medication overuse headache is not usually a sign of a primary neck disorder; rather, it is a symptom of medication overuse headache itself.
Concomitant depression and anxiety are comorbid with episodic migraine, but appear to be more common with medication overuse headache. Treating the depression or anxiety does not restore an episodic pattern of migraine; weaning from the overused medications remains the most important intervention. A frequent clinical error is to diagnose and treat the psychiatric issues without recognizing medication overuse as the primary problem.
Nonrestorative sleep is almost always reported by patients with medication overuse headache. This is often due to the caffeine contained in combination analgesics or to excessive dietary caffeine intake, but it may also be part of the daily acute drug withdrawal syndrome. The sleep problems are also associated with the concomitant depression. Sleep often improves after weaning from the offending substance or substances. As with neck pain, patients do not have a primary sleep disorder—the sleep disturbance is a symptom of medication overuse headache.
Vasomotor instability. Autonomic features are commonly associated with medication overuse headache. Rhinorrhea, nasal stuffiness, and lacrimation are features of medication withdrawal, especially from opioids, and are frequently attributed to sinus disease or “sinus headaches.” Many patients undergo unnecessary sinus procedures or are given antibiotics, decongestants, and other wrong medications for incorrect diagnoses. Decongestants can cause and exacerbate medication overuse headache, so they need to be withdrawn. The sinus features generally remit when the overused migraine medications are eliminated.
Preventive medications are less effective or ineffective until the acute medications are withdrawn. Thus, prescribing prevention without weaning is usually futile, and the patients are often dismissed as having a refractory problem. At the same time, migraine-specific acute treatments, ie, triptans and ergots, are usually also less effective. When patients complain that “nothing works,” either preventively or acutely, medication overuse headache should spring to mind.
Weaning from overused medications can restore the efficacy of previously ineffective treatments at the same time that a patient is restored to an episodic headache pattern. Thus, complete weaning is the pivotal clinical intervention. Clinically, there is no spontaneous remission from rebound without absolute detoxification, maintained for months.9,19–22
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
