Opiates should be avoided
Following Dr. Rizzoli’s presentation, Dr. Gottschalk presented an argument against the use of opioids in the treatment of headache.
He began by quoting the ABIM Choosing Wisely Campaign of 2012, which concluded that fioricet and narcotics should be avoided in headache unless the patient is desperate. “As a headache specialist, I can tell you that I have not faced situations sufficiently desperate to use any of these. The American Headache Society in a series of evidence assessments has concluded similarly, that they are of no use,” said Dr. Gottschalk.
Opiates and barbiturates may also increase risk of migraine chronification. One study found that triptans are associated with low rates of chronification, at just a few percent when used fewer than 4 days a month, and about 20% per year when used 10-14 days per month. Opiate use showed a broadly similar pattern, while barbiturates showed a particularly alarming pattern: “Every level of use was associated with astronomically high rates and measurably higher at the highest level of use. For opiates, the odds ratio was about 2 – statistically significant. For barbiturates it was clearly greater than 2, whereas with triptans, the odds ratio showed a nonsignificant, slight increase in risk. And for NSAIDs, the odds ratio was, if anything, less than 1,” said Dr. Gottschalk.
He also discussed aspects of behavioral pharmacology, in which positive reinforcement associated with decreased headache may encourage repeated use of the drug. “Given these, it should be no surprise to anyone that emergency room treatment with opiates for acute migraine is clearly associated with increased recidivism for patients given those drugs,” said Dr. Gottschalk.
Opiate use is associated with increased pain sensitivity, and in the case of migraine, it may interfere with the activity of other treatments.
As for butalbital-containing compounds, they are positive-reinforcing drugs, and they are not indicated for migraine, only tension headache. There is no evidence of benefit in migraine, but butalbital is anxiolytic, which could lead an individual to increase its use.
A recent meta-analysis of therapies for episodic migraine found that hydromorphone and meperidine are less effective than standard therapies such as prochlorperazine or metoclopramide. Another study suggested that opioid use may interfere with the efficacy of NSAIDs in the emergency room environment, while a post hoc analysis of rizatriptan clinical trials found that recent opiate use was associated with a lower response rate, and the effect was more pronounced in women.
Among patients with chronic migraine, a 2004 study found that opiates were the most commonly used medication, and other studies found that chronic migraine does not arise in nonmigraine patients treated with opiates, “suggesting that migraine is specifically prone to opiate-induced hyperalgesia of migraine itself,” said Dr. Gottschalk.
Even under careful monitoring, misuse occurs in more than 50% of patients, “suggesting that even under the best circumstances, it is difficult to use this class of drugs safely in long term,” said Dr. Gottschalk.
He pointed out that the risk of drug addiction rises with various clinical and socioeconomic factors, including living in impoverished environments, adverse childhood experiences, low socioeconomic status, exposure to pollutants, and stressors. “In other words, all features associated with systemic racism are clearly associated with an increased risk of addiction,” said Dr. Gottschalk. Other factors include availability of the drug, such as whether or not a physician prescribes it, and repeated use.
These concerns, combined with positive-reinforcing properties of opiates and association with migraine progression and refractoriness, and the lack of progression risk found with use of NSAIDs and triptans, and the fact that effective acute therapy is associated with a lower risk of progression, argue against the use of opiates, said Dr. Gottschalk.
There is even a potential risk that the experience of migraine and its relief due to self-administration may become a rewarding experience that propagates the problem. It’s possible that anticipatory anxiety related to fear stressors could lead to migraine, or to physical sensations interpreted as migraine prodrome. “[It] raises the question of whether or not positive reinforcement by drugs makes migraine itself a rewarding experience and therefore more likely to occur as a cue for drug self-administration. The question I pose is: Is there any reason to test this theory in drugs of no proven benefit in the treatment of migraine? I would say very clearly, No,” said Dr. Gottschalk.