Headaches Caused by Medication Overuse

Educational Objectives

The goal of this program is to improve prevention and treatment of medication overuse headache. After hearing and assimilating this program, the clinician will be better able to:

1. Identify patients at high risk for medication overuse headache.
2. Minimize risk for medication overuse headache among patients being treated for migraine.
3. Appropriately use drugs that are preventative against migraine in patients with medication overuse headache.

Summary

Early experience with medication overuse headache (MOH): use of phenacetin, dispensed in the form of aspirin-phenacetin-caffeine, was found to increase the frequency and severity of headache, which prompted the Food and Drug Administration to withdraw this drug from the market; a similar phenomenon was observed with ergotamine

Migraines and MOH: migraines are recurring headaches with full recovery between episodes; people who overuse medications begin to develop the same phenomenology as those with chronic migraine, ie, headache becomes the baseline, with periodic paroxysms; patients may report having chronic tension headaches as well as migraines, or having many different types of headache; 5% of the population has chronic daily headaches; MOH is found in 1% to 2% of the population, including children and adults; studies suggest that 80% of chronic migraine is triggerable by medication overuse

Early intervention: recommended for use of triptans, which tend to be most effective if taken at the onset of migraine; may result in less use of medication over the course of the day; becomes problematic if this recommendation prompts overuse (ie, the utility of early intervention depends on the frequency of migraines)

Migraine and MOH: most patients with MOH are migraineurs (but it may occur in patients with other types of headache syndromes); patients taking analgesics for other pain syndromes (eg, arthritis) do not develop de novo headaches that subsequently become continuous headache; in migraineurs, taking analgesics for reasons other than headache also increases risk for MOH

Chronic migraines: frequency of headaches, persistence of headaches, and nausea are features associated with chronification of headaches; allodynia, a condition in which pain in elicited by a stimulus that normally is not painful, also is a feature of chronic migraine; other factors associated with chronification of headache include depression, anxiety, other pain disorders (eg, fibromyalgia), obesity, asthma, snoring, stress, and poor treatment efficacy; the likelihood of worsening of headache over time also is linked to the number, severity, and duration of attacks; “medication underuse headache” — undertreating migraines is a major risk factor for worsening over time; cutaneous allodynia is observed in undertreated migraines

Recognition of medication overuse: taking medication as part of daily activity is a warning sign; when clinicians advise patients to reduce medication use, they often experience worsening headache, leading to loss of confidence in the clinician; therefore, counseling patients about expectations is important

Recurrence of migraines: defined as return of migraine within 24 hr of relief; recurrence tends to occur after 8 to 12 hr after taking sumatriptan and some other triptans; recurrences that occur in <8 hr typically are related to other factors

Diagnostic criteria for MOH: when associated with triptans, migraine features are typical; MOH with other drugs typically produces a tension-type, less descript headache syndrome; improvement over time after discontinuation is no longer included in the criteria

Pathophysiology of MOH: believed to be related to central sensitization; in addition to increase in the frequency of headache, there is an expansion in the region of pain; at the start of a migraine, first-order neuron pain (in the V1 branch of the trigeminal nerve, around the eye and the temple) is typical; once it enters second- and third-order neurons (eg, the thalamus), pain becomes generalized; there is chronic background pain, with progressive development of cutaneous allodynia; in the setting of MOH, nociceptive chemicals increase in the cerebrospinal fluid; 5-HT2A receptors are upregulated, which increases intracellular calcium, leading to greater expression of nitric oxide synthase and, eventually, increased cortical spreading depression

Imaging and MOH: functional magnetic resonance imaging shows reduced activity in the supramarginal gyrus on the right side and superior and inferior parietal cortex; this effect normalizes after several months of detoxification; there is an increase in volume of the periaqueductal gray in MOH

Medications and risk for MOH: opioids, ergotamine, butalbital, and caffeine are strongly associated with MOH; other drugs that can cause MOH include nasal decongestants, oral decongestants, triptans, marijuana, dihydroergotamine (DHE; unlikely), neuroleptics, and naproxen sodium; gepants (eg, Rimegepant) are available for the preventive and episodic treatment of migraine; a study by Bigal et al found opioids and barbiturates increase risk for MOH, nonsteroidal anti-inflammatory drugs are protective at low and moderate doses, and triptans are neutral (controversial); cannabinoids — if given continuously, ▵-9-tetrahydrocannabinol produces antinociception and causes allodynia, which worsens over time but resolves with discontinuation; according to a study presented at an American Academy of Neurology meeting, risk for MOH is increased 6-fold among users of cannabinoids (ie, although cannabinoids often are used to treat migraine, their propensity to cause MOH limits utility as an ongoing treatment)

Gauging overuse: emphasis shifted from number of pills per week to number of days of use per week; drug half-lives — drugs with shorter half-lives may be suitable for more frequent use; there may be a dissociation between half-life and duration of action; drugs with long half-lives but short durations of action are not optimal (eg, butalbital has a duration of action of ≈4 hr but a half-life of 61 hr); the speaker suggests never giving a drug more often than 5 half-lives

Summary of causes of MOH: overuse of acute medication; suboptimally effective medication (ie, patients may be less likely to overuse highly effective medications); early intervention paradigms; use of psychoactive drugs; consumption of caffeine (can cause MOH, even in young children); opioids (can cause MOH even with short-term use)

Psychiatric comorbidities of migraine: include major depression, panic disorder, obsessive-compulsive disorder, anxiety, and social phobias; many of these are bidirectional factors and are observed in family members; different psychiatric comorbidities predispose patients to preferences for particular drugs (eg, depression and caffeine, anxiety and barbiturates); when given opioids, nondepressed people often become dysphoric, but dysphoric people often become euphoric; this line of reasoning is further supported by the fact that individuals who overuse triptans (which have no psychoactive properties) are also those with the lowest rate of psychiatric comorbidities; the drug being overused may provide clues to a patient’s underlying psychiatric comorbidities

Discontinuation of migraine therapy: some drugs can be stopped abruptly, while others must be tapered; bridge therapy — often necessary; patients should be counseled about the reasons for limits on the quantity of bridge medication; use a class of drug other than that the patient has been overusing; options include steroids, dopamine antagonists, gepants, repetitive DHE, and metoclopramide; preventative medication — can be given while weaning off the overused drug; options include topiramate, valproate, onabotulinumtoxinA, some triptans, olanzapine, mexiletine, methylergonovine, and calcitonin gene-related peptide monoclonal antibodies; nonpharmacologic treatment — includes biofeedback, cognitive behavioral therapy, acupuncture, stress management, and migraine devices; gepants — important in MOH because of their effectiveness in treatment and prevention of migraine

Behavioral determinants: many patients with MOH are psychologically dependent on analgesics; “cephalgiaphobia” — individuals with a fear of migraines may begin to take drugs pre-emptively; there are genetic commonalities between MOH and substance abuse

Readings

Bigal ME, Lipton RB. Modifiable risk factors for migraine progression. Headache. 2006;46(9):1334-1343. doi:10.1111/j.1526-4610.2006.00577.x; Bigal ME, Serrano D, Buse D, Scher A, et al. Acute migraine medications and evolution from episodic to chronic migraine: a longitudinal population-based study. Headache. 2008;48(8):1157-1168. doi:10.1111/j.1526-4610.2008.01217.x; Dodick DW, Turkel CC, DeGryse RE, et al. OnabotulinumtoxinA for treatment of chronic migraine: pooled results from the double-blind, randomized, placebo-controlled phases of the PREEMPT clinical program. Headache. 2010;50(6):921-936. doi:10.1111/j.1526-4610.2010.01678.x; Fischer MA, Jan A. Medication-overuse headache. StatPearls Publishing. 2021 Jul 19. Available from: https://www.ncbi.nlm.nih.gov/books/NBK538150/; Green MW. Editorial: A 2021 update on migraine. Curr Opin Neurol. 2021;34(3):329. doi:10.1097/WCO.0000000000000939; Green MW. Medication overuse headache. Curr Opin Neurol. 2021;34(3):378-383. doi:10.1097/WCO.0000000000000925; Schwedt TJ, Chong CD. Medication overuse headache: pathophysiological insights from structural and functional brain MRI research. Headache. 2017;57(7):1173-1178. doi:10.1111/head.13037.

Disclosures

In adherence to ACCME Standards for Commercial Support, Audio Digest requires all faculty and members of the planning committee to disclose relevant financial relationships within the past 12 months that might create any personal conflicts of interest. Any identified conflicts were resolved to ensure that this educational activity promotes quality in health care and not a proprietary business or commercial interest. For this program, the following has been disclosed: Dr. Green reported nothing to disclose. The planning committee reported nothing to disclose. In his lecture, Dr. Green presents information related to the off-label or investigational use of a therapy, product, or device.

Acknowledgements

Dr. Green was recorded at the Headache Update 2021, held July 15-18, 2021, in Lake Buena Vista, FL, and presented by the Diamond Headache Clinic Research and Educational Foundation, Chicago, IL. For information on future CME activities from this presenter, please visit www.diamondheadache.com. Audio Digest thanks the speakers and meeting presenters for their cooperation in the production of this program.

CME/CE INFO

Accreditation:

The Audio- Digest Foundation is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

The Audio- Digest Foundation designates this enduring material for a maximum of 0 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Audio Digest Foundation is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's (ANCC's) Commission on Accreditation. Audio Digest Foundation designates this activity for 0 CE contact hours.

Lecture ID:

NE122302

Expiration:

This CME course qualifies for AMA PRA Category 1 Credits™ for 3 years from the date of publication.

Instructions:

To earn CME/CE credit for this course, you must complete all the following components in the order recommended: (1) Review introductory course content, including Educational Objectives and Faculty/Planner Disclosures; (2) Listen to the audio program and review accompanying learning materials; (3) Complete posttest (only after completing Step 2) and earn a passing score of at least 80%. Taking the course Pretest and completing the Evaluation Survey are strongly recommended (but not mandatory) components of completing this CME/CE course.

Estimated time to complete this CME/CE course:

Approximately 2x the length of the recorded lecture to account for time spent studying accompanying learning materials and completing tests.