CNS Drugs

, Volume 24, Issue 11, pp 929–940 | Cite as

Innovative Delivery Systems for Migraine

The Clinical Utility of a Transdermal Patch for the Acute Treatment of Migraine
  • Alan M. Rapoport
  • Fred Freitag
  • Starr H. Pearlman
Review Article


Migraine is a disabling, painful primary headache disorder that is associated with various combinations of neurological, gastrointestinal, autonomic and pain symptoms. Gastrointestinal disturbances associated with migraine, including nausea and vomiting, affect a majority of migraineurs and often result in a delay in taking or avoidance of pharmacological intervention. Gastric stasis and vomiting may lead to delayed or inconsistent absorption of orally administered medications. Many migraineurs awake early in the morning with their attack progressing and already associated with nausea and vomiting. As a result, there is a need for a novel, non-invasive, non-oral delivery system for fast and effective acute treatment of migraine.

There are two non-oral delivery systems currently available in the US for the acute treatment of migraine: three nasal sprays and two injectable formulations. Although nasal sprays depend partially on nasal mucosal absorption, a significant amount of drug is swallowed, transits the stomach and is absorbed in the small intestine, which is not as rapid or effective a route of delivery for those migraineurs with gastric stasis. Sumatriptan is rapidly absorbed by subcutaneous injection with or without a needle, but the invasiveness and discomfort of the delivery, the high incidence of adverse events and the high recurrence rate all limit its use for many patients. Iontophoretic delivery of medication is a non-invasive transdermal approach that uses small amounts of electrical current to promote rapid movement of the ionized drug through the skin and into the systemic circulation. This delivery bypasses hepatic first-pass metabolism and also avoids gastric transit delay and slowing of small intestinal absorption associated with gastrointestinal stasis in migraineurs.

Two pharmacokinetic studies have demonstrated that iontophoretic transdermal delivery of sumatriptan results in rapid and consistent achievement of therapeutic plasma concentrations. These studies also suggest that, by avoiding patient exposure to a rapid rise in and high plasma concentrations of sumatriptan as seen with injectable sumatriptan, transdermal delivery using iontophoresis may significantly reduce typical triptan-related adverse events. A large, randomized, double-blind, placebo-controlled, multicentre clinical trial showed statistically significant efficacy, good tolerability and virtually no triptan-related adverse events.

Iontophoretic delivery of sumatriptan, with a novel transdermal patch device, offers patients a migraine-specific medication that is non-invasive and non-oral. Clinically, transdermal delivery provides rapid and effective relief of migraine while bypassing the gastrointestinal tract, with minimal classic triptan-related adverse effects. This unique approach facilitates the rapid absorption of this migraine-specific triptan, which should improve the chances of consistently achieving a therapeutic plasma concentration of sumatriptan, resulting in effective migraine relief.



Funding for this project was provided by NuPathe. Drs Rapoport, Freitag and Pearlman have received consulting honoraria from NuPathe (manufacturers of Zelrix).


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Copyright information

© Adis Data Information BV 2010

Authors and Affiliations

  • Alan M. Rapoport
    • 1
  • Fred Freitag
    • 2
  • Starr H. Pearlman
    • 3
  1. 1.Department of NeurologyThe David Geffen School of Medicine at UCLALos AngelesUSA
  2. 2.Department of Family MedicineRosalind Franklin University of Medicine and ScienceNorth ChicagoUSA
  3. 3.Department of BiologyArmstrong Atlantic State UniversitySavannahUSA

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