S5:Ep12 – Understanding Medication Overuse Headache (Rebound Headache)



Voice-over: Welcome to Spotlight on Migraine hosted by the Association of Migraine Disorders. Join us for fresh perspectives by medical experts and advocates as we explore the spectrum of migraine and dig deeper into this complex disease.

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In this episode, Dr. Sait Ashina talks to us about medication-overuse headache, also known as rebound or medication-adaptation headache. He discusses how it occurs, who is more likely to develop it, and how to prevent or break the headache cycle.

Molly O’Brien: Hello, and welcome to Spotlight on Migraine. I’m your host, Molly O’Brien. Today, we’re going to talk about medication-overuse headache. You might also know it as rebound or medication-adaptation headache.

To help us learn all about medication-overuse headache, I’d like to welcome our guest, Dr. Sait Ashina. Dr. Ashina is an assistant professor of neurology and anesthesia at Harvard Medical School. He’s the director of the Comprehensive Headache Center at Beth Israel Deaconess Medical Center.

Dr. Ashina, thanks so much for joining us today.

Sait Ashina, MD: Thank you, and thank you for the kind introduction and invitation to talk about this very interesting topic.

O’Brien: It’s so interesting, and it seems like medication overuse is a vicious cycle that I feel like more people within the migraine and headache community are learning about and becoming aware of. So we want to know about it all. So if we can start off by chatting today, just explain what is medication-overuse headache.

Ashina: Yes, of course. Medication-overuse headache was first described by Peters and Horton in 1951 at Mayo Clinic, and they have called these conditions with different names. This condition had names of rebound headaches, drug-overuse headaches, drugs-induced headaches, medication misuse, or medication-adaptation headache. But in 1988, the International Headache Society proposed the criteria for medication-overuse headaches and called it a secondary headache disorder. Secondary headache means that there are headaches which are arising as a result of underlying medical condition in contrast to the primary headache disorders. So it could be a problem with a neck injury, sinus infection, and worst case, tumors, for example, causing the secondary headaches.

So over the years, the diagnostic criteria for medication-overuse headaches have evolved, and the current classification requires at least 15 or more days with the headaches per month along with the use of specific, acute-headache medications or treatments exceeding certain thresholds for a minimum of 3 months, in patients with preexisting headaches disorders. It’s very interesting. So medication-overuse headache occurs when the pain-relieving medications or anti-migraine drugs are used too frequently or excessively to treat ongoing headache attacks. And it’s very important to differentiate from the prophylactic treatments because these medications we take on a daily basis to prevent the headaches from coming.

So surprisingly, the very medications which initially provide relief from headache can actually trigger subsequent headaches if the relief is given too often, which is counterintuitive, a little bit. And so to receive this diagnosis, as I mentioned, you need to have at least 15 days per month with the headaches, occurring for at least 3 months. And along with these headaches, patients can also experience symptoms of nausea, vomiting, sensitivity to light and sounds, irritability, difficulty concentrating, insomnia, restlessness, and sometimes constipation.

O’Brien: And like you said, it’s tough. It’s almost like a catch-22 because you’re taking the pain medication because you have headache, but then taking pain medication too much can actually cause headache. So frustrating. Can you explain how rebound or medication-overuse headache actually happens, how it occurs?

Ashina: So the pain relievers and anti-migraine medications can effectively alleviate the headaches when taken as needed. However, in patients with primary headache disorders or other headache disorders, for example, with migraines or tension-type headache, these patients should be cautious about using these medications excessively because taking these medications on 2 or more days per week can actually trigger medication-overuse headaches.

And, you know, as you mentioned, it’s very interesting and very counterintuitive and fascinating why this is happening, but the exact underlying mechanisms for medication-overuse headaches are not fully understood. But there are several hypotheses. It’s believed that medication overuse can affect the neural pathways involved in a primary headache disorder, particularly in those occurring with migraines. Genetic factors may play a role. Certain gene variations are associated with metabolic abnormalities. We call them like serotonergic, dopaminergic transmissions. They kind of involved in the processing of chemicals. And even pathways involved in drug dependence have been involved in this headache.

We have also looked at neuroimaging studies, and these studies have shown that there are structural and functional, even metabolic changes in the brains of individuals with medication-overuse headaches. And specific areas, for example, of the brain, like we call them, they’re involved in the pain processing and also in emotional control of the pain, like hippocampus, periaqueductal gray, we call it thalamus, cerebellum, cingulate cortex. Those areas, interestingly, are showing alterations in patients with medication-overuse headache.

And we also know that there is some sort of the cortical excitability, so excitability of the cortex of the brain, the outermost layer of the human brain, which makes the patients vulnerable to develop these headaches. And finally, what happens is when the patients overuse these medications, the central sensitization or the activation of the neuronal networks or pain pathways is happening, and then the pain gets out of control, it becomes chronic.

O’Brien: We do know that medication-overuse headache is fairly common. Is there any one type of person or patient that is more likely to develop medication overuse or more at risk to develop this?

Ashina: So very interesting question. So medication-overuse headache affects over half of patients with chronic headaches, essentially with those who have headaches on 15 or more days per month, with an estimated 59 million people worldwide who are affected by these headaches. And those occurrences rates or prevalence rates are ranging anywhere from 1% to 2% of general population. And in a specialized headache center like mine, prevalence can be as high as 50% to 80% of our patients can have this headache.

There are some studies that have shown there are risk factors for medication overuse. In other words, if you have those risk factors, you are more likely to develop medication-overuse headache. For example, some patients with a lower socioeconomic group or certain ethnic groups have higher rates. Studies have shown that. Women in their thirties and fifties are more commonly affected.

And, you know, medication-overuse headache is a disabling condition. It’s ranked among the top 20 diseases carrying years of life lost due to disability. So medication overuse occurs in 15% of migraine patients and is associated with higher pain sensitivity, with increased sensitivity to touch, which we call allodynia.

So triptan, opioids, barbiturate users are more likely to develop medication-overuse headache. While, for example, interestingly, people who take medications like ibuprofen or non-steroidal anti-inflammatory drugs have a lower likelihood. But I’m still cautious with these patients as well. I would recommend them to still limit the use of headache-abortive medications to no more than 9 to 10 days per month, if possible.

And it’s very interesting that one of the strongest risk factors for medication overuse are the use of opioids or barbiturate-containing medications. There’s one medication commonly known as Fioricet, for example, that’s a brand name, which gives a higher risk of medication-overuse headache.

O’Brien: Dr. Ashina, you mentioned some medications, people who use certain medications could be at higher risk, but can you talk a little bit more about some of those drugs that can push people over into rebound or medication-overuse headache.

Ashina: Essentially, any headache-abortive medication can contribute to rebound headaches or medication-overuse headaches. For instance, individuals with migraine are frequently using over-the-counter medications such as acetaminophen or Tylenol, known as Tylenol, ibuprofen, known as Advil or Motrin, or naproxen, known as Aleve, on more than 15 days per month, and they are at risk for developing medication-overuse headaches.

The same applies to those taking those combination medications, for example, commonly known as the popular medication Excedrin. It has, for example, caffeine, aspirin, and acetaminophen in it, so 3 medications or 3 drugs in one drug. And these patients who can overuse this medication can be at risk for this type of headache.

And another one, which I mentioned to you before, was the barbiturate-containing medications, commonly known as Fioricet or Fiorinal. Additionally, individuals who use triptans like sumatriptan or Imitrex or ergot alkaloids, which has Cafergot, the medication is Cafergot, or opioids on more than 10 days per month are also susceptible for developing the medication-overuse headaches.

O’Brien: So now that we know a little bit more about the drugs that can push people over into rebound, can we talk about what it feels like? What are some of the symptoms of medication-overuse headache? Because someone that might be living with episodic migraine, they might think, oh, I just have a tension headache today, so I’m going to take more medicine. It can be tough to determine the difference. So what are some of the symptoms of medication overuse?

Ashina: Yes, that’s exactly right. It’s sometimes very difficult to make a diagnosis. As a matter of fact, most patients with medication overuse have either migraine or tension-type headache like picture of headaches, or they can have both headaches. They typically experience chronic and frequent headaches, and at times, it could be even daily, and it’s often with superimposed migraine-like attacks. And in headache centers, for example, our patients may have daily or nearly daily headaches.

And typically, this analgesic overuse can lead to so-called diffuse or holocranial, involving the whole head, dull pressure-like headache, with some associated migraine features or symptoms. For example, triptan overuse can cause daily migraine-like headaches and resolve briefly after you stop the medications. And with increasing headache frequency, associated symptoms like nausea, vomiting, and light sensitivity, and sound sensitivity may decrease in patients with migraine, and it could look like or sound like it’s tension headache.

On average, patients with these headaches have suffered from these chronic headaches for 20 years and have been overusing medications for at least 6 years, which again emphasizes the need for better awareness of this headache among patients and clinicians. So misdiagnosis, unsuccessful treatment attempts can contribute to irrational medication use.

And it’s very important to evaluate for coexisting conditions such as depression, anxiety, and other medical conditions which can guide the clinicians and the patients in terms of the treatment decisions. And it’s also important for clinicians, as well as for the patients, be cautious about the medications and for clinicians, especially cautious about prescribing additional acute headache medications that can lead to this cycle of medication-overuse headache.

O’Brien: I think that’s so important that patients and clinicians need to be aware of this and be honest with each other about what medications you’re taking and how often you’re taking them. Because when we know, then it helps with the diagnosis.

So the big question is, I think, if someone is experiencing medication-overuse headache, if they’re in this vicious cycle, how do you break it? How do you get out of this? And can you?

Ashina: Yes, we absolutely can. So medication-overuse headaches usually stop when a person stops taking the headache medication. It may be difficult in the beginning because once you stop the medication, the headache can get worse before it gets better. But we can offer our patients the medications to prevent the headaches. And some other non-medical therapies can also be used, such as biofeedback, avoiding triggers, and they can help the person to get through this medication-withdrawal period.

Typically, the treatment of medication overuse involves both nonpharmacological approaches, pharmacological approaches, and the pausing or discontinuing the overused medication. And among the nonpharmacologicals, education is a very important, awareness about this headache. It has been shown that if you implement education and awareness, it reduces the medication use and headache frequency in patients. Education can be provided in both specialist centers and primary care offices. Even pharmacists can educate their patients about the overuse of medications.

Pharmacological treatments involve preventative treatments. It can be with withdrawal or without withdrawal of medication. These include, for example, they’ve been shown that topiramate, onabotulinum toxin A, commonly known as the Botox, monoclonal antibodies targeting CGRP, which is one novel drug for migraine, have demonstrated efficacy in treating patients with chronic migraine and medication overuse. Topiramate can be effective but may be limited because of the side effects, and then we have some other medication which can be better tolerated.

Some studies have also shown that blood pressure-lowering medications, such as beta-blockers and some calcium channel blockers can be used also in patients with medication-overuse headache. And lastly, patients who can take so-called tricyclic antidepressants, which is antidepressant medication used for prevention of migraine or tension-type headache. And lastly, candesartan, which is another blood pressure medication has been used in practice for relieving this headache.

O’Brien: And detoxing from any drug medication can be really challenging. It can be very difficult. So can you talk to people out there who might be experiencing medication-overuse headache, what are the benefits of detoxing? Because most of the time your symptoms are going to get worse before they get better, but what’s on the other side of that? Give some people some hope.

Ashina: And Molly, you bring a very interesting point. The concept of medication-overuse headache and its treatment has always been uncomfortable one for clinicians and the patients. As advice to minimize and discontinuing medications provide acute relief, headache seems kind of like contradicting the mission of minimizing the pain.

However, we know that reducing the frequency of taking acute medications has been shown to be one of the most effective treatments of medication overuse. And it can be performed both in the clinic settings or outpatient settings or in hospital settings. And discontinuation of medication in some patients with opioid and barbiturates can be challenging and could be done in inpatient settings and under supervision of physician or close supervision of a physician.

Other factors such as, as I mentioned before, psychiatric comorbidities like anxiety and depression, overuse of several other medications from classes, prior failed outpatient treatment, withdrawal therapy are also relative indications for inpatient treatment. There was actually a recent randomized clinical study suggesting that withdrawal therapy or discontinuation overuse medication, combined with preventative medication from start of the withdrawal is effective treatment strategy for medication-overuse headache.

Another approach would be switching from the overused medication to alternative acute medication, used with a limited frequency, and they can also help to relieve this problem. And think of preventative treatments. So preventive treatment can be initiated during the acute-medication withdrawal, and in further course, regular follow-up visits. Preventative medical treatments are given to prevent relapses or renewed overuse of acute-headache medications.

We recommend to patients to keep the diaries and keep their doctors updated about the progress or any problems, for sure, contact their physicians.

O’Brien: That’s good to know that you can start some preventative treatments as you are detoxing from acute treatments. So that’s good to know that there doesn’t have to be a big gap in care. There is help available out there. And like you said, I think it’s important for people to know that when you are detoxing from certain medications, it is best advised to be under guidance of a doctor.

Well, let’s kind of not necessarily switch gears, but I have a different question. Because we know that some people are at higher risk of developing medication-overuse headache, what is a person with migraine or primary headache disorder supposed to do if they need to take these types of medications? Say they have chronic pain issues, they have an injury, you know, cold medicine has acetaminophen in it. Or maybe they have surgery, so they need opioid medication for pain relief or management. What should someone do if they need to take these types of medications at a higher frequency that might push them over into medication overuse?

Ashina: Yeah, this can be a challenging situation, especially in a person who has preexisting headache disorder. I think it’s really important to consult with a healthcare professional, discuss your concerns as a patient, talk about the specific medication needs, and also get some understanding about the underlying conditions. In that way, the doctor can give some sort of personalized guidance and develop a plan how to manage the pain.

It is important to keep to the recommended dosages to avoid the risk of escalating the medications and stick to the guidelines and discuss with their physicians, And if the patients experience severe pain, address that.

It is very important to explore alternative treatments, for example, nonmedication alternatives to pain relief. For example, if the patient has knee pain, for example, or back pain, and is in need to take acetaminophen on daily basis or another analgesic, in that situation, the patient can discuss with his or her primary care physician about any other referrals, for example, to physical therapy, or the pain physician, as well, to discuss, for example, treatments with interventional treatments like blocks, etc.

And it is also important to consider preventative strategies. So as I mentioned before, so if there is a high risk of overuse because the patient have to take acetaminophen every day for another problem, then consider starting the patient on preventative treatments for headaches.

O’Brien: When you first start talking about medication-overuse headache, it kind of seems like, gah, what am I going to do? But it does seem like there are strategies and ways to avoid getting into this situation, and if you do get into it, there are ways to get out. So there is help out there, there are resources out there, which is good to know and helpful to know.

Ashina: Absolutely. Absolutely. The prognosis of medication overuse is generally good, with 50% to 70% of patients demonstrating improvement after withdrawal therapy, especially in combination with prevention with medications. However, there may be some patients, like 10% to 40%, who may relapse within 5 years after withdrawal. And the first year is considered critical, time where you need to really monitor the patient, and that can predict the long-term success.

And the combination of migraine and tension headache, use of opioids, longer duration of acute-medication intake, and high number of acute treatments intake and high number of acute treatments for up to 2 months of withdrawal. Interestingly, smoking, alcohol, and patient-reported poor sleep quality, and just body aches can be risk factors of relapse. So therefore, as both the clinicians and patients need to be aware of that and closely monitor for any recurrence of medication overuse and act promptly.

O’Brien: That’s good to know. And I was going to ask, as we kind of wrap up here, do we know anything about potential long-term effects of medication-overuse headache? Like, if you have it once, are you more likely to get it again or more likely rebound within 5 years, like you were mentioning? Or say you have episodic migraine, you go into rebound. Are you more likely to develop chronic migraine? Like those are just some examples. But do we know any long-term effects?

Ashina: Yes, if the person has a medication overuse and has episodic migraine, there’s high likelihood of developing chronic migraine. This has been shown in observational studies. And we know that from our clinical experience.

There’s another problem with overuse of medications, their side effects, you know, they can affect the liver, kidneys, other than causing or triggering the medication-overuse headache, and so this also needs to be monitored for.

And as I mentioned to you, the general prognosis is good, but there are some people who can relapse. And I already mentioned there are some risk factors for relapse. And in those cases, it’s very important for a physician to be aware of the situations and monitor the patient closely. This can be done by frequent follow-ups, for example, seeing the patients more often, especially in that critical time.

O’Brien: Absolutely. Well, thank you so much, Dr. Ashina, for helping us understand and get a better comprehension of medication-overuse headache. I would like to say thank you, once again, for joining us, and we really appreciate all your insight today.

Ashina: Thank you, Molly. Thank you for your invitation.

O’Brien: And thanks to all of our followers for watching this episode of Spotlight on Migraine. I’m your host, Molly O’Brien. We’ll see you next time.

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