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. Physicians worry about episodic migraine converting to chronic daily headache, but this worry can also lead to under-treatment and even stigmatization of patients who aggressively treat their symptoms.
These concerns and others were a topic of a debate at the Headache Cooperative of New England’s 20th Annual HCNE Boston Fall Headache Symposium, which was conducted virtually.
The International Classification of Headache-3 (ICHD-3) defines medication overuse headache as a headache that occurs on 15 or more days per month in a patient with pre-existing primary headache, and that develops because of regular overuse of acute or symptomatic headache medication. The ICHD-3 also says that headache usually resolves when overuse is stopped, though not always.
Paul Rizzoli, MD, took issue with that definition. “If you have a lot of headaches and you take medication for them, then you likely have medication overuse headache. They say the most common cause of symptoms suggestive of chronic migraine is medication overuse. That’s like saying, if you have a rash on your arm, then it is an allergic sun exposure rash. No need to characterize the rash,” said Dr. Rizzoli, who is clinical director of the John R. Graham Headache Center at Brigham and Women’s Faulkner Hospital in Boston, during the session.
Is medication overuse really the culprit?
Dr. Rizzoli began by emphasizing that taking a lot of medication is always a concern. “Significant hepatic and renal and GI toxicities can result from taking and overusing medication of all sorts. What (I am) questioning is whether or not this rather strange, arbitrary, fluidly-defined concept of abortive migraine medicine overuse is truly responsible for causing all of the ills of which it is accused – and just as importantly, if the proposed solution for it, which is to just stop the overused medication and all will be better – if that solution is the right or wrong advice to give to a patient,” he said.
Much of Dr. Rizzoli’s criticism rested on the definition of medication overuse syndrome. He believes that many concerns about medication overuse can be traced to the use of opiates or barbiturate-containing medications, which have known propensities to lead to headaches. Other cases are less well defined, and “it’s not quite clear what the pathophysiology of the condition is – whether or not it’s the same as rebound or withdrawal headache, or if it is the same as a pronociceptive effect of analgesics, also called medicine-induced headache. Both are well documented and accepted, and the idea of opioid-induced analgesia tolerance is well documented and has several plausible mechanisms attributed to it,” said Dr. Rizzoli.
He said that changes in structural imaging in the brain suggest there at least two subgroups of patients that are both labeled as having medication overuse headache, one from medication overuse and one from progression of migraine disease. “Based on physiology, medication overuse headache cannot be clearly seen as a unitary condition,” he said.
Dr. Rizzoli cited other research on triptans, opioids, and barbiturates that showed an overall conversion from episodic migraine to chronic migraine, with the lowest frequency occurring in patients taking acetaminophen, aspirin, and caffeine (2%), followed by NSAIDs (4%), triptans (4%), opioids (5%), and barbiturates (6%). A total of 52 patients who became chronic were taking triptans, on average 7 days per month. The 1,370 triptan-using patients who remained episodic took triptans on average 5 days per month. “Does this seem like a huge difference between these two groups? The transformation rate in just this triptan subgroup was about 3%-4%, suggesting that, compared with the overall transformation rate of 3%, use of triptans did not exert much force overall on the baseline rate,” he said. Similar patterns were visible with use of other classes of drugs.
Meanwhile, the higher rates of conversion seen with opioids and barbiturates suggests an effect from these drugs. “Perhaps this data suggests the previously known effect is at play here and argues against the need for a separate diagnosis of medication overuse headache,” Dr. Rizzoli said.
“The evidence that simple analgesics can cause medication overuse headache is especially weak, and the evidence that NSAIDs do is conflicting, with some evidence suggesting they’re protective at some doses.” Other population studies suggested most patients with daily headache do not overuse medications, and studies in India, where analgesics are rarely used, still showed a similar rate of conversion to daily headache. Other studies failed to show evidence that withdrawal of overused medication leads to improvement. “Studies of populations after aggressive management of medicine overuse headache indicate that, for the majority of the headaches, for the most part did not clear after treatment, except maybe for a short time,” said Dr. Rizzoli.
A systematic review of 18 population studies showed the prevalence of medical overuse headache ranged from 11% to 68%. “That indicates substantial uncertainty about the magnitude of the problem,” said Dr. Rizzoli.
He also noted potential harms to patients. Many patients come in experience between 10 and 20 headaches per month. “To see them out of medical overuse would have us advising not to treat half of their headaches monthly in order to avoid this evil. Many patients who have read or heard about this condition are themselves restricting treatment so as to avoid medication overuse headache. The harms of such undertreatment have not been fully investigated.”
To get at the issue, he recommended adapting the traditional number-needed-to-treat calculation. “You could calculate a number needed to overtreat. If medication use is assumed to be the sole cause of headache chronification, the calculations could suggest you would need to restrict therapy for about 4 people for each person you protect from going chronic. That’s a lot of undertreatment,” said Dr. Rizzoli.
He summed up by saying that some patients may have a progressive disorder with structure and physiological changes in the brain that result in chronic pain, and such patients should be identified and studied. In others with frequent headache, high medication use may simply be associated with the condition becoming chronic, but not causative. “These diagnostic groups may be mixed and may be difficult to untangle,” said Dr. Rizzoli.
Medication overuse is to blame
Dr. Rizzoli’s debate lecture was followed by Barbara Nye, MD, who argued that concerns over medication overuse headache are valid. She noted a more unifying definition in ICHD-3, which requires regular medication overuse for at least 3 months, along with primary headache disorder.
Dr. Nye, who is codirector of the Headache Clinic at Dartmouth-Hitchcock Medical Center in Lebanon, N.H., related her experience that medication overuse headache often occurs more quickly than the 3-month time frame contained in ICHD-3, especially in patients who were given pain medications after undergoing surgery. She echoed Dr. Rizzoli’s concerns about opiates and barbiturates. “Medicine overuse headache should be something we focus on, and we should be warning providers both in neurology and primary care about the frequent use of opiate and butalbital-containing medications, and frequent over-the-counter medicine use in high-frequency headache disorders,” Dr. Nye said during her talk.
She cited research showing risk factors for conversion from episodic to chronic daily headache. As well as medication overuse, these include White race, lower education status, previous marriage, obesity, diabetes, arthritis, top-quartile caffeine use, stressful life events, and higher headache frequency.
Risks vary by medication class. Opiates and narcotics used more than 2 or 3 times per week are of particular concern, as are short-acting over-the-counter medicines used more than three times per week or 10-15 days per month. She agreed that NSAIDs may have a protective effect, but only at much lower doses and when used about five (or fewer) times per month. One study showed a possible protection effect of NSAIDs, though when used more than 10 days/month, they were associated with medication overuse headache.
Fioricet and Fiorinal, used more than 1 day/week, have an early and robust medicine overuse effect. “Limiting that use is very important,” said Dr. Nye. Other medicines and doses of concern include Tramadol/Ultram used at a higher than 50 mg/day dose, which has a metabolite that causes headache, and triptans used more than 10 days/month.
These concerns came about after analysis of large trials in patients with other conditions who also suffer from episodic migraines. A study of patients with irritable bowel syndrome and migraine showed a risk of conversion with opioid treatment. Another study of patients with arthritis and episodic migraine showed an association between conversion and NSAIDs alone, NSAIDs combined with Tylenol, and NSAIDs combined with opioids.
Risks of medication overuse also included collateral damage to the gastrointestinal and kidney systems, development of dependence, exacerbation of depression, and opioid-induced hyperalgesia, according to Dr. Nye. The overused medication may also interfere with the use of preventive medication. Those concerns drive the conventional wisdom of weaning patients off the overused medication, Dr. Nye said.
Dr. Nye discussed some of the observations of structural changes in the brain found in episodic migraine and chronic migraine associated with medication overuse. Functional MRI showed changes in grey matter, both as a result of medication overuse headache and further changes after medication withdrawal. “A lot of neuroplasticity and neuroadaptation occurs, and these effects seem to be sustained anywhere from 4-6 months after (medicine) discontinuation,” said Dr. Nye.
Common ground
Dr. Nye emphasized the need to be aware of the dangers of medication overuse headache, but noted that clinicians should address the problem to ensure that patients are empowered, potentially providing preventive medications and encouraging more effective use of daily abortive medications.
In response, Dr. Rizzoli suggested that the two agreed on many issues. For her part, Dr. Nye agreed that medication overuse headache is a muddy concept that needs more research to understand the relationship between opiate use and chronic migraine, “but I do think there have been some good studies of fMRI evaluating the difference between those with medication overuse headache and seeing how they convert back to a different underlying network (following medication withdrawal). I do agree that there is probably a subpopulation that is not affected by medication overuse headache,” Dr. Nye said.
In the end, both expressed concerns for the patient. “I share Barbara’s concern that we need to be mindful and protect our patients from medication use, but on the other hand I think we also need to protect our patients from the complications of having a diagnosis of medical overuse and the stigmatization that goes with that. That particular issue goes both ways,” said Dr. Rizzoli.
“I absolutely agree with that,” responded Dr. Nye.
Dr. Nye is on the advisory boards for Biohaven, Upsher Smith, and Impel. She is a trial site principal investigator for Allergan, Amgen, and Satsuma. Dr. Rizzoli has been a consultant for Nestle and served on the scientific advisory or data safety monitoring board for Biohaven and Xoc Pharma. He has also received research support from Allergan.
. Physicians worry about episodic migraine converting to chronic daily headache, but this worry can also lead to under-treatment and even stigmatization of patients who aggressively treat their symptoms.
These concerns and others were a topic of a debate at the Headache Cooperative of New England’s 20th Annual HCNE Boston Fall Headache Symposium, which was conducted virtually.
The International Classification of Headache-3 (ICHD-3) defines medication overuse headache as a headache that occurs on 15 or more days per month in a patient with pre-existing primary headache, and that develops because of regular overuse of acute or symptomatic headache medication. The ICHD-3 also says that headache usually resolves when overuse is stopped, though not always.
Paul Rizzoli, MD, took issue with that definition. “If you have a lot of headaches and you take medication for them, then you likely have medication overuse headache. They say the most common cause of symptoms suggestive of chronic migraine is medication overuse. That’s like saying, if you have a rash on your arm, then it is an allergic sun exposure rash. No need to characterize the rash,” said Dr. Rizzoli, who is clinical director of the John R. Graham Headache Center at Brigham and Women’s Faulkner Hospital in Boston, during the session.
Is medication overuse really the culprit?
Dr. Rizzoli began by emphasizing that taking a lot of medication is always a concern. “Significant hepatic and renal and GI toxicities can result from taking and overusing medication of all sorts. What (I am) questioning is whether or not this rather strange, arbitrary, fluidly-defined concept of abortive migraine medicine overuse is truly responsible for causing all of the ills of which it is accused – and just as importantly, if the proposed solution for it, which is to just stop the overused medication and all will be better – if that solution is the right or wrong advice to give to a patient,” he said.
Much of Dr. Rizzoli’s criticism rested on the definition of medication overuse syndrome. He believes that many concerns about medication overuse can be traced to the use of opiates or barbiturate-containing medications, which have known propensities to lead to headaches. Other cases are less well defined, and “it’s not quite clear what the pathophysiology of the condition is – whether or not it’s the same as rebound or withdrawal headache, or if it is the same as a pronociceptive effect of analgesics, also called medicine-induced headache. Both are well documented and accepted, and the idea of opioid-induced analgesia tolerance is well documented and has several plausible mechanisms attributed to it,” said Dr. Rizzoli.
He said that changes in structural imaging in the brain suggest there at least two subgroups of patients that are both labeled as having medication overuse headache, one from medication overuse and one from progression of migraine disease. “Based on physiology, medication overuse headache cannot be clearly seen as a unitary condition,” he said.
Dr. Rizzoli cited other research on triptans, opioids, and barbiturates that showed an overall conversion from episodic migraine to chronic migraine, with the lowest frequency occurring in patients taking acetaminophen, aspirin, and caffeine (2%), followed by NSAIDs (4%), triptans (4%), opioids (5%), and barbiturates (6%). A total of 52 patients who became chronic were taking triptans, on average 7 days per month. The 1,370 triptan-using patients who remained episodic took triptans on average 5 days per month. “Does this seem like a huge difference between these two groups? The transformation rate in just this triptan subgroup was about 3%-4%, suggesting that, compared with the overall transformation rate of 3%, use of triptans did not exert much force overall on the baseline rate,” he said. Similar patterns were visible with use of other classes of drugs.
Meanwhile, the higher rates of conversion seen with opioids and barbiturates suggests an effect from these drugs. “Perhaps this data suggests the previously known effect is at play here and argues against the need for a separate diagnosis of medication overuse headache,” Dr. Rizzoli said.
“The evidence that simple analgesics can cause medication overuse headache is especially weak, and the evidence that NSAIDs do is conflicting, with some evidence suggesting they’re protective at some doses.” Other population studies suggested most patients with daily headache do not overuse medications, and studies in India, where analgesics are rarely used, still showed a similar rate of conversion to daily headache. Other studies failed to show evidence that withdrawal of overused medication leads to improvement. “Studies of populations after aggressive management of medicine overuse headache indicate that, for the majority of the headaches, for the most part did not clear after treatment, except maybe for a short time,” said Dr. Rizzoli.
A systematic review of 18 population studies showed the prevalence of medical overuse headache ranged from 11% to 68%. “That indicates substantial uncertainty about the magnitude of the problem,” said Dr. Rizzoli.
He also noted potential harms to patients. Many patients come in experience between 10 and 20 headaches per month. “To see them out of medical overuse would have us advising not to treat half of their headaches monthly in order to avoid this evil. Many patients who have read or heard about this condition are themselves restricting treatment so as to avoid medication overuse headache. The harms of such undertreatment have not been fully investigated.”
To get at the issue, he recommended adapting the traditional number-needed-to-treat calculation. “You could calculate a number needed to overtreat. If medication use is assumed to be the sole cause of headache chronification, the calculations could suggest you would need to restrict therapy for about 4 people for each person you protect from going chronic. That’s a lot of undertreatment,” said Dr. Rizzoli.
He summed up by saying that some patients may have a progressive disorder with structure and physiological changes in the brain that result in chronic pain, and such patients should be identified and studied. In others with frequent headache, high medication use may simply be associated with the condition becoming chronic, but not causative. “These diagnostic groups may be mixed and may be difficult to untangle,” said Dr. Rizzoli.
Medication overuse is to blame
Dr. Rizzoli’s debate lecture was followed by Barbara Nye, MD, who argued that concerns over medication overuse headache are valid. She noted a more unifying definition in ICHD-3, which requires regular medication overuse for at least 3 months, along with primary headache disorder.
Dr. Nye, who is codirector of the Headache Clinic at Dartmouth-Hitchcock Medical Center in Lebanon, N.H., related her experience that medication overuse headache often occurs more quickly than the 3-month time frame contained in ICHD-3, especially in patients who were given pain medications after undergoing surgery. She echoed Dr. Rizzoli’s concerns about opiates and barbiturates. “Medicine overuse headache should be something we focus on, and we should be warning providers both in neurology and primary care about the frequent use of opiate and butalbital-containing medications, and frequent over-the-counter medicine use in high-frequency headache disorders,” Dr. Nye said during her talk.
She cited research showing risk factors for conversion from episodic to chronic daily headache. As well as medication overuse, these include White race, lower education status, previous marriage, obesity, diabetes, arthritis, top-quartile caffeine use, stressful life events, and higher headache frequency.
Risks vary by medication class. Opiates and narcotics used more than 2 or 3 times per week are of particular concern, as are short-acting over-the-counter medicines used more than three times per week or 10-15 days per month. She agreed that NSAIDs may have a protective effect, but only at much lower doses and when used about five (or fewer) times per month. One study showed a possible protection effect of NSAIDs, though when used more than 10 days/month, they were associated with medication overuse headache.
Fioricet and Fiorinal, used more than 1 day/week, have an early and robust medicine overuse effect. “Limiting that use is very important,” said Dr. Nye. Other medicines and doses of concern include Tramadol/Ultram used at a higher than 50 mg/day dose, which has a metabolite that causes headache, and triptans used more than 10 days/month.
These concerns came about after analysis of large trials in patients with other conditions who also suffer from episodic migraines. A study of patients with irritable bowel syndrome and migraine showed a risk of conversion with opioid treatment. Another study of patients with arthritis and episodic migraine showed an association between conversion and NSAIDs alone, NSAIDs combined with Tylenol, and NSAIDs combined with opioids.
Risks of medication overuse also included collateral damage to the gastrointestinal and kidney systems, development of dependence, exacerbation of depression, and opioid-induced hyperalgesia, according to Dr. Nye. The overused medication may also interfere with the use of preventive medication. Those concerns drive the conventional wisdom of weaning patients off the overused medication, Dr. Nye said.
Dr. Nye discussed some of the observations of structural changes in the brain found in episodic migraine and chronic migraine associated with medication overuse. Functional MRI showed changes in grey matter, both as a result of medication overuse headache and further changes after medication withdrawal. “A lot of neuroplasticity and neuroadaptation occurs, and these effects seem to be sustained anywhere from 4-6 months after (medicine) discontinuation,” said Dr. Nye.
Common ground
Dr. Nye emphasized the need to be aware of the dangers of medication overuse headache, but noted that clinicians should address the problem to ensure that patients are empowered, potentially providing preventive medications and encouraging more effective use of daily abortive medications.
In response, Dr. Rizzoli suggested that the two agreed on many issues. For her part, Dr. Nye agreed that medication overuse headache is a muddy concept that needs more research to understand the relationship between opiate use and chronic migraine, “but I do think there have been some good studies of fMRI evaluating the difference between those with medication overuse headache and seeing how they convert back to a different underlying network (following medication withdrawal). I do agree that there is probably a subpopulation that is not affected by medication overuse headache,” Dr. Nye said.
In the end, both expressed concerns for the patient. “I share Barbara’s concern that we need to be mindful and protect our patients from medication use, but on the other hand I think we also need to protect our patients from the complications of having a diagnosis of medical overuse and the stigmatization that goes with that. That particular issue goes both ways,” said Dr. Rizzoli.
“I absolutely agree with that,” responded Dr. Nye.
Dr. Nye is on the advisory boards for Biohaven, Upsher Smith, and Impel. She is a trial site principal investigator for Allergan, Amgen, and Satsuma. Dr. Rizzoli has been a consultant for Nestle and served on the scientific advisory or data safety monitoring board for Biohaven and Xoc Pharma. He has also received research support from Allergan.
. Physicians worry about episodic migraine converting to chronic daily headache, but this worry can also lead to under-treatment and even stigmatization of patients who aggressively treat their symptoms.
These concerns and others were a topic of a debate at the Headache Cooperative of New England’s 20th Annual HCNE Boston Fall Headache Symposium, which was conducted virtually.
The International Classification of Headache-3 (ICHD-3) defines medication overuse headache as a headache that occurs on 15 or more days per month in a patient with pre-existing primary headache, and that develops because of regular overuse of acute or symptomatic headache medication. The ICHD-3 also says that headache usually resolves when overuse is stopped, though not always.
Paul Rizzoli, MD, took issue with that definition. “If you have a lot of headaches and you take medication for them, then you likely have medication overuse headache. They say the most common cause of symptoms suggestive of chronic migraine is medication overuse. That’s like saying, if you have a rash on your arm, then it is an allergic sun exposure rash. No need to characterize the rash,” said Dr. Rizzoli, who is clinical director of the John R. Graham Headache Center at Brigham and Women’s Faulkner Hospital in Boston, during the session.
Is medication overuse really the culprit?
Dr. Rizzoli began by emphasizing that taking a lot of medication is always a concern. “Significant hepatic and renal and GI toxicities can result from taking and overusing medication of all sorts. What (I am) questioning is whether or not this rather strange, arbitrary, fluidly-defined concept of abortive migraine medicine overuse is truly responsible for causing all of the ills of which it is accused – and just as importantly, if the proposed solution for it, which is to just stop the overused medication and all will be better – if that solution is the right or wrong advice to give to a patient,” he said.
Much of Dr. Rizzoli’s criticism rested on the definition of medication overuse syndrome. He believes that many concerns about medication overuse can be traced to the use of opiates or barbiturate-containing medications, which have known propensities to lead to headaches. Other cases are less well defined, and “it’s not quite clear what the pathophysiology of the condition is – whether or not it’s the same as rebound or withdrawal headache, or if it is the same as a pronociceptive effect of analgesics, also called medicine-induced headache. Both are well documented and accepted, and the idea of opioid-induced analgesia tolerance is well documented and has several plausible mechanisms attributed to it,” said Dr. Rizzoli.
He said that changes in structural imaging in the brain suggest there at least two subgroups of patients that are both labeled as having medication overuse headache, one from medication overuse and one from progression of migraine disease. “Based on physiology, medication overuse headache cannot be clearly seen as a unitary condition,” he said.
Dr. Rizzoli cited other research on triptans, opioids, and barbiturates that showed an overall conversion from episodic migraine to chronic migraine, with the lowest frequency occurring in patients taking acetaminophen, aspirin, and caffeine (2%), followed by NSAIDs (4%), triptans (4%), opioids (5%), and barbiturates (6%). A total of 52 patients who became chronic were taking triptans, on average 7 days per month. The 1,370 triptan-using patients who remained episodic took triptans on average 5 days per month. “Does this seem like a huge difference between these two groups? The transformation rate in just this triptan subgroup was about 3%-4%, suggesting that, compared with the overall transformation rate of 3%, use of triptans did not exert much force overall on the baseline rate,” he said. Similar patterns were visible with use of other classes of drugs.
Meanwhile, the higher rates of conversion seen with opioids and barbiturates suggests an effect from these drugs. “Perhaps this data suggests the previously known effect is at play here and argues against the need for a separate diagnosis of medication overuse headache,” Dr. Rizzoli said.
“The evidence that simple analgesics can cause medication overuse headache is especially weak, and the evidence that NSAIDs do is conflicting, with some evidence suggesting they’re protective at some doses.” Other population studies suggested most patients with daily headache do not overuse medications, and studies in India, where analgesics are rarely used, still showed a similar rate of conversion to daily headache. Other studies failed to show evidence that withdrawal of overused medication leads to improvement. “Studies of populations after aggressive management of medicine overuse headache indicate that, for the majority of the headaches, for the most part did not clear after treatment, except maybe for a short time,” said Dr. Rizzoli.
A systematic review of 18 population studies showed the prevalence of medical overuse headache ranged from 11% to 68%. “That indicates substantial uncertainty about the magnitude of the problem,” said Dr. Rizzoli.
He also noted potential harms to patients. Many patients come in experience between 10 and 20 headaches per month. “To see them out of medical overuse would have us advising not to treat half of their headaches monthly in order to avoid this evil. Many patients who have read or heard about this condition are themselves restricting treatment so as to avoid medication overuse headache. The harms of such undertreatment have not been fully investigated.”
To get at the issue, he recommended adapting the traditional number-needed-to-treat calculation. “You could calculate a number needed to overtreat. If medication use is assumed to be the sole cause of headache chronification, the calculations could suggest you would need to restrict therapy for about 4 people for each person you protect from going chronic. That’s a lot of undertreatment,” said Dr. Rizzoli.
He summed up by saying that some patients may have a progressive disorder with structure and physiological changes in the brain that result in chronic pain, and such patients should be identified and studied. In others with frequent headache, high medication use may simply be associated with the condition becoming chronic, but not causative. “These diagnostic groups may be mixed and may be difficult to untangle,” said Dr. Rizzoli.
Medication overuse is to blame
Dr. Rizzoli’s debate lecture was followed by Barbara Nye, MD, who argued that concerns over medication overuse headache are valid. She noted a more unifying definition in ICHD-3, which requires regular medication overuse for at least 3 months, along with primary headache disorder.
Dr. Nye, who is codirector of the Headache Clinic at Dartmouth-Hitchcock Medical Center in Lebanon, N.H., related her experience that medication overuse headache often occurs more quickly than the 3-month time frame contained in ICHD-3, especially in patients who were given pain medications after undergoing surgery. She echoed Dr. Rizzoli’s concerns about opiates and barbiturates. “Medicine overuse headache should be something we focus on, and we should be warning providers both in neurology and primary care about the frequent use of opiate and butalbital-containing medications, and frequent over-the-counter medicine use in high-frequency headache disorders,” Dr. Nye said during her talk.
She cited research showing risk factors for conversion from episodic to chronic daily headache. As well as medication overuse, these include White race, lower education status, previous marriage, obesity, diabetes, arthritis, top-quartile caffeine use, stressful life events, and higher headache frequency.
Risks vary by medication class. Opiates and narcotics used more than 2 or 3 times per week are of particular concern, as are short-acting over-the-counter medicines used more than three times per week or 10-15 days per month. She agreed that NSAIDs may have a protective effect, but only at much lower doses and when used about five (or fewer) times per month. One study showed a possible protection effect of NSAIDs, though when used more than 10 days/month, they were associated with medication overuse headache.
Fioricet and Fiorinal, used more than 1 day/week, have an early and robust medicine overuse effect. “Limiting that use is very important,” said Dr. Nye. Other medicines and doses of concern include Tramadol/Ultram used at a higher than 50 mg/day dose, which has a metabolite that causes headache, and triptans used more than 10 days/month.
These concerns came about after analysis of large trials in patients with other conditions who also suffer from episodic migraines. A study of patients with irritable bowel syndrome and migraine showed a risk of conversion with opioid treatment. Another study of patients with arthritis and episodic migraine showed an association between conversion and NSAIDs alone, NSAIDs combined with Tylenol, and NSAIDs combined with opioids.
Risks of medication overuse also included collateral damage to the gastrointestinal and kidney systems, development of dependence, exacerbation of depression, and opioid-induced hyperalgesia, according to Dr. Nye. The overused medication may also interfere with the use of preventive medication. Those concerns drive the conventional wisdom of weaning patients off the overused medication, Dr. Nye said.
Dr. Nye discussed some of the observations of structural changes in the brain found in episodic migraine and chronic migraine associated with medication overuse. Functional MRI showed changes in grey matter, both as a result of medication overuse headache and further changes after medication withdrawal. “A lot of neuroplasticity and neuroadaptation occurs, and these effects seem to be sustained anywhere from 4-6 months after (medicine) discontinuation,” said Dr. Nye.
Common ground
Dr. Nye emphasized the need to be aware of the dangers of medication overuse headache, but noted that clinicians should address the problem to ensure that patients are empowered, potentially providing preventive medications and encouraging more effective use of daily abortive medications.
In response, Dr. Rizzoli suggested that the two agreed on many issues. For her part, Dr. Nye agreed that medication overuse headache is a muddy concept that needs more research to understand the relationship between opiate use and chronic migraine, “but I do think there have been some good studies of fMRI evaluating the difference between those with medication overuse headache and seeing how they convert back to a different underlying network (following medication withdrawal). I do agree that there is probably a subpopulation that is not affected by medication overuse headache,” Dr. Nye said.
In the end, both expressed concerns for the patient. “I share Barbara’s concern that we need to be mindful and protect our patients from medication use, but on the other hand I think we also need to protect our patients from the complications of having a diagnosis of medical overuse and the stigmatization that goes with that. That particular issue goes both ways,” said Dr. Rizzoli.
“I absolutely agree with that,” responded Dr. Nye.
Dr. Nye is on the advisory boards for Biohaven, Upsher Smith, and Impel. She is a trial site principal investigator for Allergan, Amgen, and Satsuma. Dr. Rizzoli has been a consultant for Nestle and served on the scientific advisory or data safety monitoring board for Biohaven and Xoc Pharma. He has also received research support from Allergan.
FROM HCNE’S 20TH ANNUAL BOSTON FALL HEADACHE SYMPOSIUM