Advancements in Nasal Sprays for Migraine Treatment


The director of the Jefferson Headache Center at Jefferson University Hospital discusses the problem with traditional nasal sprays and how improvements in formulation and delivery can improve efficacy.

Stephen D. Silberstein, MD

Stephen D. Silberstein, MD

While nasal spray-based therapies may seem like a convenient treatment option for patients with migraine, traditional formulations and delivery systems have fallen short. Often, drug delivery is compromised and in turn, treatment efficacy does not reach its peak. Recently, updated drug formulations and redesigned delivery methods have been associated with improved outcomes.1

NeurologyLive spoke with Stephen D. Silberstein, MD, professor of neurology and director, Jefferson Headache Center at Jefferson University Hospital in Philadelphia, about these new developments and how they might change the treatment landscape for migraine headache.

NeurologyLive: What are the challenges with traditional nasal sprays for migraine?

Stephen Silberstein, MD: The problem with typical nasal spray delivery is for one, it doesn't get to the right spot in the nose and it falls out. The other problem with typical nasal spray delivery is that it doesn’t rapidly get absorbed. There are ways around this: you can make it a solid, or you can add enhancers to the composition to drive absorption. For example, there are older DHE liquid nasal sprays that have poor bioavailability that take a long time to get into the system. With the newer concept of redesigning the formulations and delivery method, it means that the bioavailability is better and the time it takes to get into the system is faster. Speed and rapid peak are what counts in the treatment of acute migraine.

How does this newer drug delivery design compare to existing treatments in terms of efficacy?

If you can create a nasal formulation of DHE with kinetics similar to an injection, you’re going to dramatically enhance how effective it is compared to the pre-existing DHE nasal sprays.

Do you feel that nasal spray delivery is a preferred method for patients compared with oral or injection-based treatments?

Most patients prefer oral, but the problem with oral delivery systems is that it’s slow and sometimes the bioavailability is limited. In terms of DHE, it gets metabolized and it has no benefit taken by mouth. Patients prefer nasal sprays to injections but some of the older nasal sprays tasted horrible, so the issue is not so much people not liking nasal sprays, it’s that they don't like nasal sprays that taste horrible.

Transcript edited for clarity


Shrewsbury SB, Jeleva M, Satterly KH, Lickliter J, Hoekman J. STOP 101: A phase 1, randomized, open-label, comparative bioavailability study of INP104, dihydroergotamine mesylate (DHE) administered intranasally by a i123 Precision Olfactory Delivery (POD) device, in healthy adult subjects. Headache. 2019;59(3):394-409.

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