Current and Emerging Therapies for the Treatment and Prevention of Migraine: An Interview With Stephen D. Silberstein, MD

Stephen D. Silberstein, MD, is the director of the Headache Center at Jefferson University Hospital in Philadelphia, Pennsylvania. He is certified by the United Council for Neurologic Subspecialties in Headache Medicine and is a fellow of the American Academy of Neurology, the American College of Physicians, and the American Neurological Association. He is also a member and past president of the American Headache Society. An editor from The American Journal of Managed Care^® recently conducted an interview with Dr Silberstein on the treatment and prevention of migraine.

The American Journal of Managed Care^®

(AJMC^®): From your perspective, what are some of the unmet needs in acute migraine treatment and in migraine prevention?

Stephen D. Silberstein, MD: The most important unmet need from my perspective is for a patient to get a diagnosis and [to determine] if their physician is capable of taking care of a patient with migraine. If a patient is having trouble getting good care from their physician, they need to find a physician who has expertise in headaches. It’s not often that new treatments are needed; rather, existing treatments need to be used appropriately. For example, the dose is often too low or the treatment duration is too short. Patients may receive treatment for a week instead of a month.

Another problem is that patients take medicine frequently for acute migraine [and] preventive medications often will not work until those daily medications have been eliminated. For example, a patient could be taking triptans or Excedrin every day. That’s medication overuse, and it is a silent epidemic. These patients will not get better until medication overuse is eliminated.

[After addressing medication overuse,] we can determine which of our existing medicines are appropriate for the acute treatment of migraine in that patient. No drug works in every patient. It is important to note that if a patient does not respond to 1 drug, that does not mean they will be unresponsive to another.

Triptans are the most commonly used medications for the treatment of migraine; however, they do not always work and they are contraindicated in the presence of cardiovascular disease. They also have side effects, so we need alternatives. These alternatives include gepants, new formulations of dihydroergotamine [DHE], lasmiditan, and medical devices.

Gepants are small molecule CGRP [calcitonin gene-related peptide] antagonists. The major advantage is that they do not have the cardiovascular risk that is associated with the triptans.

DHE is often effective when triptans are not; however, it is also contraindicated in the presence of cardiovascular disease. Therefore, DHE would be for patients without any contraindications who may not be getting adequate response to triptans.

Lasmiditan is similar to a triptan, but it does not cause vasoconstriction and thus would be used in patients in whom there is a contraindication to triptans.

There are many drugs that are used for prevention, but none of them work 100% of the time, and some of them have side effects. Until recently, very few drugs were FDA-approved specifically for migraine prevention.

The preexisting drugs include beta-blockers, topiramate, Depakote [divalproex], tricyclic antidepressants, and some of the SNRIs [serotonin-norepinephrine reuptake inhibitors]. The 2 new classes of drugs that were approved for the prevention and treatment of migraines are Botox [onabotulinumtoxinA] and monoclonal antibodies. Botox is approved for patients with chronic, frequent migraine. The monoclonal antibodies, including 1 that is directed against the CGRP receptor and another that is directed against CGRP itself, have been shown to be safe and effective in preventing migraine.

In terms of nondrug options for treatment and prevention, yoga is effective in migraine prevention, and biofeedback and relaxation techniques are effective in migraine treatment.

Treatment of migraine does not mean choosing A or B or C. Rather, it involves picking the best [option] for the patient, which may be a combination of A, B, and C.

AJMC^®

: What is the role of nondrug treatments such as noninvasive vagus nerve stimulation and single-pulse transcranial magnetic stimulation in acute migraine treatment and prevention?

Silberstein: The treatment and prevention of migraine is going from ‘evolution’ to ‘revolution.’

Nondrug treatment can be used as an alternative or in addition to medicines. For example, in a patient who is taking a combination of medicines and getting a partial response, we may increase the dose of medication. At the increased dose, the patient may get a better response, but they may experience side effects. At that time, we may add 1 of the devices. These devices are also a good choice when patients are unable or unwilling to take medications; for example, if they might be pregnant or if they are breastfeeding.

Medical devices on the market for the acute treatment of migraine and prevention include a vagus nerve stimulator and a transcranial magnetic stimulator. Another device [the Nerivio Migra device, which uses noninvasive neuromodulation] from Theranica was approved by the FDA in May 2019 [for the acute treatment of migraine].

AJMC^®

: How do you select among the available treatment and preventive options for an individual patient?

Silberstein: When you go out to dinner, how do you decide on what you are going to eat? I do not say that facetiously. Treatment selection is based on a conversation between the doctor and the patient. It comes down to choice, safety, and affordability.

For example, there are patients who do not want to take medicines, and so you might give them 1 of the devices to have when they need it. However, some of the devices are expensive and they may not be covered by insurance. Before taking a standard preventative drug, patients may want to try nutraceuticals for which there is scientific evidence regarding efficacy. Or, if a patient has infrequent headache, they might just want to take an over-the-counter nonsteroidal [anti-inflammatory drug] before trying something else.

OnabotulinumtoxinA can only be used for chronic migraine and the patient has to fail 2 standard preventative drugs before it will be approved. One of the advantages of onabotulinumtoxin type A is, you give the shot, it stays in the skin and lasts for 3 months, which means that you do not have to worry about it traveling throughout the body.

Before using the antibodies, the patient also has to fail 2 standard preventative drugs. An advantage of the antibodies is that they last for a long time, but that also means that if a patient wants to get pregnant, they have to wait 4 or 5 months [after they have stopped the drug].

AJMC^®

: Could you describe the impact of migraine prevention on patients, caregivers, family members, and employers?

The most common reaction I receive once a patient is on a migraine preventative that works is that I’ve given them their life back. They can interact socially, they can be with their families, and they can work effectively. Imagine having a migraine every day of your life, and now you only have 1 or 2 a month.

AJMC^®

: From your standpoint, how do managed care policies impact patient access to medications for acute migraine treatment or migraine prevention?

Silberstein: Several barriers exist. First, there are 10 or 15 [managed care] companies, all with different rules. Second, [managed care] companies make it difficult for patients to get certain medicines by requiring failure of multiple other drugs. Furthermore, they have been known to limit access to some triptans and may make it difficult for patients to get approval to see a specialist. These barriers can waste time and money.

To simplify healthcare, we need a national registry for drugs and national rules and regulations for using them so physicians do not have to spend a lot of time figuring out what every [managed care] company is doing differently. Instead of having to go to 10 different websites to find out if a treatment is approved for a patient or what is needed for approval, a physician would only have to visit 1 website.

Medicare, in general, does not require preapproval, so it’s easier to navigate. They either say ‘yes’ or ‘no.’ For example, if you want to prescribe Botox to a patient, you do it, and bill Medicare. If you want to prescribe Botox to a patient on another insurance, it can take hours and days to get approval. If [managed care] companies could simplify [the process], that would make life easier for everyone.

AJMC^®

: What does the future hold for patients with migraine? What can we look forward to within the next 5 to 10 years?

Silberstein: We have seen amazing breakthroughs in the treatment and prevention of migraine over the past 5 or 10 years and we are seeing more treatments every day. Investigators are now studying ketamine for intractable migraine. They are also studying new drugs based on another neuropeptide, PACAP-38 [pituitary adenylyl cyclase activating peptide-38].

I’m excited for the future for patients with migraine. We just need patients to be taken seriously. Also, we need more resources and we need to fix the issues with insurance coverage.