. 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. Paul Rizzoli
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.