Selecting a treatment plan to deal with acute migraine attacks can be like putting together a toolkit of possible therapies, individualized for each patient, one expert said.
The toolkit should comprise reliable treatments that patients know are going to work and that act quickly, allowing them to get back to functioning normally in their daily lives, said Jessica Ailani, MD, during a talk at the 17th European Headache Congress held recently in Barcelona, Spain.
"Everyone with migraine needs acute treatment," Ailani, who is a clinical professor of neurology at MedStar Georgetown University Hospital and director of the Georgetown Headache Center, Washington, DC, noted. "Sometimes we can reduce acute treatment with preventative agents, but some disability will remain, so we have to focus on good acute treatment, and this becomes more complex if a person has a lot of comorbidities, which is common in older patients."
In selecting suitable treatments, consideration has to be given to the patient profile, any other conditions they have, speed of onset of the migraine attack, length of the attack, associated symptoms, and side effects of the medications, she said.
As an example, Ailani described the process she used to treat one of her patients who had frequent severe migraines and other issues causing difficult decisions when selecting medications — a woman in her late 60s with several other comorbidities.
"The is the kind of case I see on a daily basis and which keeps me up at night," she said. "Many times in clinical practice, we see complex cases like this, and through the course of a year, we may try every treatment option we have in a patient like this."
On the first presentation, the patient had a chronic migraine with severe headaches every day. She had a history of previous cervical discectomy with fusion surgery; uncontrolled hypertension, for which she was taking an angiotensin blocker; high cholesterol, for which she was taking a statin; and diabetes with an A1c of 8. She did not smoke or drink alcohol, exercised moderately, and her body mass index was in a good range.
"Before a patient ever sees a doctor for their migraine, they will have already tried a lot of different things. Most people are already using NSAIDs and acetaminophen, the most commonly used treatments for acute migraine," Ailani explains.
Her patient was taking a triptan and the barbiturate, butalbital. Ailani notes that the triptan is very effective, but in the United States, they are not available over the counter, and the patient is only allowed nine doses a month on her insurance, so she was supplementing with butalbital.
Over the course of a year, Ailani got her off the butalbital and started her on onabotulinum toxin A for migraine prevention, which reduced her headache days to about 15 per month (8 severe). She then added the anti-calcitonin gene-related peptide (CGRP) monoclonal antibody, galcanezumab, as another preventative, which further reduced the headache days down to 8-10 days per month (all migraine).
The attacks are rapid onset and can last multiple days. They come with photophobia and phonophobia and cause her to be bedridden, she noted.
"I was still worried about this frequency of headache and the fact she was using a triptan for acute treatment when she had uncontrolled hypertension and other cardiovascular risk factors," Ailani commented.
She explained that triptans are generally not used in individuals aged over 65 years because of a lack of data in this age group. They are also contraindicated in patients with cardiovascular (CV) disease, and caution is advised in patients with CV risk factors. Noting that migraine is an independent risk factor for stroke in healthy individuals, and this patient already had three other major risk factors for stroke, Ailani said she did not think a triptan was the best option.
When triptans do not work, Ailani said she thinks about dihydroergotamine, which she describes as "a great drug for long-lasting migraine" as it tends to have a sustained response. But it also has vasoconstrictive effects and can increase blood pressure, so it was not suitable for this patient.
CV risk is also an issue with nonsteroidal anti-inflammatory drugs (NSAIDs), one of the staple treatments for acute migraine.
"NSAIDs are available over the counter, inexpensive, quite effective, and have minimal immediate side effects," Ailani said. But long-term adverse events include CV events, particularly in those who already have CV risk factors, and it is now thought that NSAIDs actually carry more CV risk than triptans.
She noted that out of all the NSAIDs, celecoxib carries the lowest CV risk, and in the United States, it is available as a liquid formulation. There is also a study of ketorolac nasal spray showing it to be as effective as sumatriptan nasal spray for acute migraine.
As her patient was still going to the emergency room (ER) quite frequently at this point, Ailani prescribed ketorolac nasal spray as an emergency rescue medication which did help to reduce ER visits but did not solve the acute treatment problem.
The next option she tried was the CGRP antagonists or "gepants" because of their good tolerability.
Because her patient had long attacks, Ailani said her first choice gepant was rimegepant as it has a long half-life.
She noted that in patients who have frequent migraine attacks (> 6 migraine days per month), using rimegepant as needed has been shown to lead to migraine frequency declining over time. "This shows that if we treat acute attacks properly, we can minimize the risk of chronic migraine."
She pointed out that if a patient has prodrome that is easy to identify or has short attacks, ubrogepant may be a good option, having shown effectiveness in preventing or reducing the onset of the headache in the recently reported PROROME trial when given the day before migraine starts.
Then there is also zavegepant which is available as a nasal spray, so a good option for patients with nausea and vomiting. Ailani suggested that zavegepant as a third-generation gepant may be worth trying in patients who have tried the other gepants, as it is a different type of molecule.
For this patient, neither rimegepant nor ubrogepant worked. "We tried treating in the prodrome, when the pain was starting, adding to other treatments, but she is not a 'gepant' responder. We have yet to try zavegepant," she said.
The next consideration was lasmiditan. "This patient is a triptan responder and lasmiditan is a 5HT1 agonist, so it makes sense to try this. Also, it doesn't have a vasoconstrictor effect as it doesn't work on the blood vessels, so it is safe for patients with high blood pressure," Ailani noted.
She pointed out, however, that lasmiditan has become a rescue medication in her practice because of side effect issues such as dizziness and sleepiness.
But Ailani said she has learned how to use the medication to minimize the side effects, by increasing the dose slowly and advising patients to take it later in the day.
"We start with 50 mg for a few doses then increase to 100 mg. This seems to build tolerability."
Her patient has found good relief from lasmiditan 100 mg, but she can't take it during the day as it makes her sleepy.
As a last resort, Ailani went back to metoclopramide which she described as "a tried and tested old-time drug."
While this does not make the patient sleepy, it has other adverse effects limiting the frequency of its use, she noted. "I ask her to try to limit it to twice a week, and this has been pretty effective. She can function when she uses it."
Ailani also points out that neuromodulation should be in everyone's tool kit. "So, we added an external combined occipital and trigeminal (eCOT device) neurostimulation device."
The patient's tool kit now looks like this:
- Neuromodulation device and meditation at first sign of an attack.
- Add metoclopramide 10 mg and acetaminophen 1000 mg.
- If the attack lasts into the second day, add lasmiditan 100 mg in the evening of the second day (limit 8 days a month).
- If the patient has a sudden onset severe migraine with nausea and vomiting that might make her go to the ER, add in ketorolac nasal spray (no > 5 days per month).
Ailani noted that other patients will need different toolkits, and in most cases, it is recommended to think about "situational prevention" for times when migraine attacks are predictable, which may include air travel, high-stress times (holidays, etc.), occasions when alcohol will be consumed, and at times of certain weather triggers.
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