Headache Horizons: Rebound Abounds in Chronic Migraine

Ask any person with migraine and they’ll tell you it is an unfair disorder. Migraine strikes without warning, may respond unpredictably to treatment, and often leaves a person feeling sick, tired, and stigmatized. Also unfair is the seemingly illogical concept that the drugs we use to treat this painful malady can also cause the symptom we’re trying to treat (Case Presentation).

Definitions and Risk Factors Abound

The concept of chronic migraine (CM) as a stand-alone entity that is separate and different from episodic migraine (EM) is relatively new, has evolved over time, and is not without controversy.¹ Although EM is far more common than CM, 3% to 4.5% of people with migraine live at the very frequent end of the monthly headache day spectrum. Over the years, this frequent headache pattern was variably termed chronic mixed headache, transformed migraine, and chronic daily headache, before the moniker chronic migraine was settled on. Regardless of its previous names, what we now call CM is defined by the International Classification of Headache Disorders, 3rd edition (ICHD-3, section 1.3) as 15 or more headache days per month, for more than 3 months, of which at least 8 headaches fulfill criteria for migraine.² It should be noted that the term episodic migraine does not appear in ICHD-3, which refers instead to migraine and chronic migraine, with the implication that anything that is not CM is, by default, EM although this is not expressly mentioned.

Multiple risk factors for CM and for progression from EM to CM have been identified (Table 1).³ Medication overuse (MO), formerly called rebound headache, is a common and important risk. With a worldwide prevalence of 1% to 2% in the general population, MO headache (MOH) is defined as a headache occurring on 1 or more days per month for 3 or more months, as a consequence of regular overuse of acute or symptomatic medications. Although MOH occurs in the setting of EM, it is much more common in those struggling with many headache days per month, such as the person with CM. It is essential to distinguish between MO and MOH (ICHD-3 section 8.2).² The former is easy to define, but the latter is more nebulous and, like CM itself, a topic of some disagreement. Use of simple analgesics (eg, ibuprofen and acetaminophen) on 15 or more days per month, or use of triptans, opioids, ergot alkaloids, or combination analgesics (eg, caffeine-acetominophen or butalbital-containing compounds) on 10 or more days per month constitutes MO. Additionally, caffeine use of more than 200 mg/day in beverages or combination analgesics increases the risk of MOH. All medicines used as acute treatment to abort migraine attacks, if taken in sufficient quantities, can lead to MO and MOH, although some have more risk for MOH than others. In a meta-analysis of 29 studies comparing the relative risk of MOH among treatment classes, analgesics and opioids carried higher risk of MOH when compared with triptans and ergots. There are also risk factors specific to the individual that increase risk of MO (Table 2).^3-5

Questions Remain

The challenge is that not every person with migraine who, by the ICHD-3 definition, overuses acute medications or caffeine and has frequent headaches has those headaches as a result of MO. Sometimes, people take more migraine medicines simply because they have more headaches. This chicken-and-egg conundrum becomes more important when we counsel persons with very frequent headaches to limit acute migraine medications to no more than 2 days per week. Our weary patient tends to look at us cross-eyed, thinking, “Great, and shall I suffer on the other 5 days of the week?” and could be forgiven if they develop a sudden urge to throw a reflex hammer at us.

It appears that MOH only is found in those who get migraines or another primary headache disorder. For instance, a person without migraine who takes simple analgesic for osteoarthritis on 25 days per month would generally not be expected to develop MOH. The concept is that the migraine-wired brain is already vulnerable and more susceptible to altered processing of pain signals induced by MO. But do all persons with migraine overusing the pain medication classes referenced above actually have MOH? Conversely, do all people with chronic daily or near daily headache with MO actually have CM, or are they merely people with EM who have chronicified the headache because of MO? And is MO a cause or consequence of CM? Approximately 50% of patients with CM and MOH, as defined by ICHD-3, will revert to having EM after stopping the agent that was overused. Of course, that means that 50% won’t, and thus likely did not have MOH, despite fitting the MO diagnosis to the letter. That explains why according to ICHD-3 guidelines, CM (a primary headache) and MOH (a secondary headache) should be coded together in the right setting, and the latter may then be rescinded if the headache pattern fails to revert to EM after a reasonable time off the (presumed) offending agent.

Treatment and Counseling

The use of acute medications in CM is often problematic, because with increasing headache frequency it is difficult to know when to dose, and easy to overdo it. In the person with near-daily or daily migraine attacks, it is often best to withhold acute migraine-specific medications until, through lifestyle changes, preventive therapy, and if needed, withdrawal of overused medications, a daylight, so to speak, arises between attacks. Then, the standard acute treatments—triptans, nonsteroidal anti-inflammatories (NSAIDs), or nasal dyhydroergotamine—may be used, being careful to limit dosing to several days per week. Use of a headache diary (paper or electronic) is helpful. Instructions should be given to stringently limit (or better yet, avoid altogether) butalbital-containing compounds, opioids, and excess caffeine. Neurostimulators, including transcranial magnetic stimulation, supraorbital stimulation, remote neurostimulation with a battery-powered arm band, or vagus nerve stimulation are being increasingly used for acute treatment of migraine, particularly for people who did not respond to standard treatments or have intolerable side effects or contraindications. The advantage of neurostimulation treatments is the lack of systemic side effects and no risk of triggering MOH to date, although cost, lack of insurance coverage, and limited data are disadvantages.

No matter what the offending agent, patients with MO must be carefully counseled to stop the offending drug. This is often challenging, as individuals frequently become heavily and emotionally invested in the MOH-inducing medication, particularly those with comorbid anxiety. Bridge therapy, such as an oral steroid taper, occipital nerve blocks, or several weeks of a long-acting NSAID (eg, nabumatone), is often helpful (Case Resolution). Individuals should be cautioned that the wash-out period may be 6 weeks or more, although it is often substantially shorter for triptan-induced MOH. It is important to note that one does not need to wash out an offending acute agent before beginning preventive therapy. Indeed, in the studies of onobotulinumtoxinA and monoclonal antibody calcitonin gene-related peptide (CGRP) inhibitors, many participants (40%-60%) met criteria for MO and fared approximately as well as those who did not have MO. The current standard of care in CM is to start a preventive therapy straightaway as an individual makes efforts to reduce or eliminate the offending medication(s).

Summary

Migraine is a common, disabling and, yes, unfair neurologic disorder. Although victories are incremental, cumulatively they can make a profound difference. Recognition and treatment of MO, particularly in an overuse-prone population, is a key part of an overall successful outcome.