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Are Your Migraine Attacks Getting Worse? It Could Be Your Medication

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If you're using a lot of medication acutely to treat frequent migraine attacks, you could be at risk of developing medication overuse headache (MOH), also called rebound headache by some. And that can feel like a catch-22: You need to treat the attacks, so what are you to do? Learn all you can here about why MOH is a concern, which medications with what frequencies put you at greatest risk, and how to treat it.

What Is Rebound Headache?

Rebound headache is not a term typically used by headache specialists but is sometimes used by the public and some healthcare providers.

When people say rebound headaches, they’re describing headaches that may be related to the increased frequency of acute medication use. When the frequently used medication wears off, the headaches come back. They may come back with greater severity than the initial headache, and they may be more resistant to treatment.

This leads people to start taking acute medications, including over-the-counter headache medications, more frequently to avoid having the headache come back. It's a vicious cycle where they may benefit initially, but then the attack returns once the level of medication drops. Over time, the system is sensitized, leading to more frequent and more severe attacks and increased resistance to treatment.

What Is Medication Overuse Headache?

MOH is a controversial but formal term describing headache on 15 or more days per month, plus the overuse of acute medications for more than three months. MOH can be either an increased frequency of typical migraine attacks or a new type of headache that lacks typical migraine features.

The criteria for overuse vary depending on the type of acute medication and its related risk of contributing to MOH. For example, the regular intake of non-opioid analgesics — such as paracetamol/acetaminophen, aspirin, ibuprofen or naproxen — on 15 or more days per month meets the criteria for medication overuse.

However, analgesics with caffeine, triptans, butalbital-containing medications, or opioids meet the criteria for overuse if there is regular intake of 10 or more days per month. An important aspect of MOH is that it improves or may even resolve if the frequently used acute medication is stopped. This does not mean that the underlying migraine will be gone, but rather that attacks of migraine will be less frequent and severe and easier to treat.

https://images.migraineagain.com/images/Migraine-Again_chart-Which-Medications-Can-Cause_-Medication-Overuse-Headache.png
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Which Medications Are the Biggest Culprits for Medication Overuse Headache?

The ones that headache specialists are most concerned about are opioids and butalbital-containing medications, meaning Fiorinal, Fioricet, or Esgic. Also, in clinical practice, one of the most common medications of concern is the aspirin, acetaminophen, caffeine combination, namely Excedrin Migraine. In the formal criteria for MOH, these medications should not be taken 10 or more days per month.

Triptan overuse is defined by regular intake on 10 or more days per month, as well. Headache specialists are concerned about people taking triptans on 10 or more days per month, but practically speaking, it is easier to manage and decrease that than somebody taking an opioid, butalbital, or combination analgesic like Excedrin Migraine on 10 or more days per month.
Migraine Again Verified Source

Vandenbussche N et al. Medication-Overuse Headache: A Widely Recognized Entity Amidst Ongoing Debate. The Journal of Headache and Pain. July 13, 2018.

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The medications that are quite controversial are the nonsteroidal anti-inflammatories (NSAIDs). In Europe, it is believed that NSAIDs, like ibuprofen or naproxen, potentially contribute to MOH. On the other side of the coin, some healthcare providers think that taking NSAIDs regularly can have preventive benefits rather than being a therapy that is “overused.”

In addition, it is a medical fact that opioids and barbiturates have the potential to cause tolerance, physical dependence, and addiction, which makes the withdrawal symptoms from these medications much more difficult to tolerate.
Migraine Again Verified Source

Diener HC et al. Pathophysiology, Prevention, and Treatment of Medication Overuse Headache. The Lancet Neurology. September 18, 2019.

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Do the Newer Migraine Drugs Cause Medication Overuse Headache? 

The development of therapies targeting calcitonin gene-related peptide (CGRP) has generated a lot of excitement — and results. For some people, they have been dramatically effective in preventing and treating migraine with minimal side effects and, so far, don’t seem to cause rebound or MOH.

Treatments that block the CGRP receptor are in a class called gepants. Those approved for the acute treatment of migraine include:

These were designed to be acute treatments, but we now also have gepants approved by the U.S. Food and Drug Administration (FDA) for preventive treatment (such as rimegepant and atogepant).

Another newer acute medication is lasmiditan (Reyvow), which acts on serotonin receptors as triptans do, but it's more specific to one type of serotonin receptor that isn't located on blood vessels. Thus, unlike triptans, this medication can be used by those with vascular disease such as prior heart attacks, stroke, or transient ischemic attacks (TIAs). 

In a study published in 2021 on the safety and risk of MOH in gepants and lasmiditan, preclinical trials suggest that lasmiditan may be associated with a certain risk for MOH (similar to that of triptans), although there currently is no data indicating that chronic use of the medication induces MOH.
Migraine Again Verified Source

Lo Castro F et al. Safety and Risk of Medication Overuse Headache in Lasmiditan and Second-Generation Gepants: A Rapid Review. Drug, Healthcare and Patient Safety. November 23, 2021.

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But in general, there is less concern about MOH when gepants are used “as needed.” According to the study, gepants may be more useful than other acute treatments in patients who have a history of MOH or are at risk of developing it, including those with frequent migraine attacks.

What Is the Treatment for Medication Overuse Headache?

The approach to MOH varies in different parts of the world. In Europe, it is believed that you should not start a new treatment until you withdraw from the “overused” medication. The rationale: Why start a new treatment when simply withdrawing from the medication may result in significant improvement?

However, in the United States, headache specialists often choose to start a migraine-specific or nonspecific preventive therapy to help people come off the overused medication and to treat the underlying primary headache disorder for which they started using the acute medication in the first place.

This approach has been used recently, with excellent success, with the monoclonal antibodies targeting CGRP. Headache specialists are seeing that even in those who are frequently taking acute medications, these preventive treatments can enable people to more easily come off the frequently used medication while simultaneously treating their underlying primary headache disorder — migraine.

Another difference is in withdrawal approaches — whether to gradually taper versus stop the medication “cold turkey.” That depends on what medication it is. For triptans and NSAIDs, there's not necessarily a physical withdrawal syndrome. But for caffeine-containing medications, such as combination analgesics like Excedrin Migraine, withdrawal can be intense. 

While caffeine can be an effective pain reliever, sudden withdrawal from it can result in unpleasant symptoms, like throbbing headaches, difficulty concentrating, fatigue, and irritability. Symptoms vary in individuals and may last anywhere from two to nine days.
Migraine Again Verified Source

Sajadi-Ernazarova KR et al. Caffeine Withdrawal. StatPearls. August 8, 2023.

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Withdrawing from other pain medications, like opioids, can be very uncomfortable, though it's not dangerous, per se. Then it becomes the individual's choice whether they want to get it over with and come off the medication rapidly or taper off on a schedule, over the course of weeks to months.

Care must be exercised when stopping the frequent use of barbiturates or butalbital because there is a very small possibility that rapid withdrawal can provoke a seizure.

What’s Wrong With the Term ‘Medication Overuse Headache’?

Advocates in the migraine community want to change the term “medication overuse” because it sounds like it puts blame on the individual who's taking the medication frequently. When acute medications are used with high frequency, it’s not your fault; it’s migraine disease. 

Another reason to change the term is to remove the sense of guilt and stigma that could be associated with frequent medication use. Some advocates, including the Coalition for Headache and Migraine Patients (CHAMP), have suggested the terms “medication adaptation headache,” “medication response headache,” or “medication misuse headache” instead. 

CHAMP also doesn’t recommend the term “rebound headache,” as it “doesn’t account for the role that medication pharmacokinetics is believed to play in this type of headache.”

The bottom line is that migraine is a disease, and it needs to be treated without assigning blame.

Can Medication Overuse Turn Episodic Migraine to Chronic Migraine?

Yes. Headache specialists believe that the increased frequency of acute medication use is a risk factor in increased frequency of migraine attacks and transition from episodic to chronic migraine. Also, healthcare providers often see the development of a new type of persistent or continuous headache when people are using acute medications frequently. 

Why Does Daily Preventive Medication Not Cause Medication Overuse Headache?

This is another somewhat controversial topic because there are preventive treatments that, upon stopping, will result in a rebound flare of attacks.

The key distinction is what happens to the attacks with medication use. Someone who is taking preventive medication should have decreased frequency and severity of attacks. By contrast, someone who is taking acute medication frequently may experience immediate relief of symptoms, but over time attacks become more frequent and severe. 

Thus, a primary differentiating factor is how someone is doing overall in terms of frequency, severity, and disability in the current setting of their medication regimen.

Any Advice for Someone Dealing With Medication Overuse Headache?

This is a situation where it is helpful for the individual to educate themselves and understand that frequent use of acute medications has the potential to sensitize the system and worsen the headache disorder in the long run.

If you find that you consistently need to use an acute medication twice a week or more, talk to your healthcare professional about initiating or adjusting a preventive treatment regimen. Neuromodulation devices, some of which are approved for the acute treatment of migraine, are adjunctive therapies that may lower the frequency of acute medication use. 

In addition, explore nonpharmacological techniques that do not involve an acute medication — such as biofeedback, mindfulness, relaxation techniques, and complementary therapies — but can help with headache pain relief and do not lead to medication overuse.

Final Thoughts

While it can be frustrating to know that some of the acute medications for migraine can lead to MOH and put you in an even worse state, at the same time, it is encouraging to know that some of the newer acute treatments, such as the gepants, pose less of a risk of MOH.

It’s important to understand that the frequent use or overuse of acute medications and the secondary headache that it may cause are not your fault. It is a complication of the underlying disease — migraine. Do not accept blame from healthcare professionals who may suggest that it is an easy process to come off of medications and that it's simply a matter of will. Because, for many individuals, it requires planning, forethought, support, and guidance.
Migraine Again Verified Source

Charles A. Migraine. The New England Journal of Medicine. August 10, 2017.

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Withdrawal from frequent medication can be difficult, but with a well-thought-out plan, agreed upon by both you and your healthcare professional, it is an achievable goal that may help you manage your migraine much more effectively moving forward.

This article was edited by Angie Glaser and Elizabeth DeStefano, based on an interview with Rebecca Brook, NP. Paula K. Dumas and Wendy Neri also contributed to the content, reviewed by Drs. Starling and Charles.

https://images.migraineagain.com/images/2020/07/andrew-charles-1.jpg
Andrew Charles, MD

Dr. Andrew Charles is the director of Headache Research and Treatment and professor of neurology at the David Geffen School of Medicine at UCLA. He leads the Goldberg Migraine Program, established in December 2015 with the largest single private grant ever for migraine research. Dr. Charles is the president of the American Headache Society, where he serves on the Board of Directors since 2010.

Dr. Charles educates neurologists, headache specialists, and primary care physicians around the world on headache research and treatment. His work has been published in numerous medical journals such as Neurology and Headache, and he serves as an associate editor of Cephalalgia. He is also a person living with migraine disease.

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