Letters to the Editor
Is Orally Inhaled Dihydroergotamine (DHE) Equivalent in Efficacy in Migraine to Intravenous DHE?
explicit statement; but no such scientific study is available. There is also no scientific evidence for the statements on similar efficacy in the 2 other reviews.1,2 In conclusion, orally inhaled DHE is better tolerated than intravenous DHE, but there is no scientific basis for stating that orally inhaled DHE has the same efficacy in migraine as intravenous DHE.
In the last 4 years, headache experts have stated in reviews1-3 that orally inhaled dihydroergotamine (DHE) has similar efficacy as intravenous DHE in the treatment of migraine attacks: In 2010, it was stated by Baron and Tepper that “INH DHE provides an improved tolerability and side effect profile, but similar efficacy to the highly therapeutic IV DHE.”1 In 2012, Silberstein stated in a review of MAP0004 (orally inhaled DHE) that2 “Pulmonary delivery of DHE using MAP0004 provides the expected anti-migraine efficacy of intravenous DHE in a more convenient formulation with fewer systemic side effects. Consequently, MAP0004 should be considered to be a first line therapy for moderate to severe migraine.”2 And in a recent review3 from 2013, Nagy and Rapoport stated: “A new oral DHE inhalation device, Levadex, has been demonstrated to provide similar onset of action and efficacy comparable to intravenous DHE.”3 So we now have 3 largely concordant statements by headache experts1-3 on orally inhaled DHE vs intravenous DHE. One of the essences in these statements is that orally inhaled DHE has fewer systemic adverse events than intravenous DHE.1,2 Based on one comparative, double-blind, pharmacokinetic comparative study4 of orally inhaled and intravenous DHE, it is most likely correct that the orally inhaled form of DHE causes less adverse events than intravenous administration of DHE. The other major point made in all 3 statements is that orally inhaled DHE has similar efficacy as intravenous DHE;1-3 and in one review, it is stated that a “new oral DHE inhalation device, Levadex, has been demonstrated to provide similar onset of action and efficacy comparable to intravenous DHE.”3 The use of the word “demonstrated” would usually imply a scientific basis, in the form of a double-blind, randomized trial, as the basis for such an
Peer Tfelt-Hansen, MD, DMSc From the Department of Neurology, Danish Headache Center, Glostrup Hospital, Glostrup, Denmark
REFERENCES 1. Baron EP, Tepper SJ. Revisiting the role of ergot alkaloids in the treatment of migraine and headache. Headache. 2010;50:1353-1361. 2. Silberstein S. MAP0004: Dihydroergotamine mesylate inhalation aerosol for acute treatment of migraine. Expert Opin Pharmacother. 2012;13:1961-1968. 3. Nagy AJ, Rapoport AM. Update on future headache treatments. Neurol Sci. 2013;34(Suppl. 1):s101-s108. 4. Shrewsbury SB, Cook RO, Taylor G, et al. Safety and pharmacokinetics of dihydroergotamine mesylate administered via a novel (Tempo) inhaler. Headache. 2008;48:355-367.
Migraine Headache Surgery The excellent article by Mathew,“A Critical Evaluation of Migraine Trigger Site Deactivation Surgery,” casts doubt on the data supporting migraine surgery.1,2 Migraine surgery is being promoted by plastic surgeons.A common statement on certain surgery sites states that “of the 60 to 80% of patients who respond to Botox, 90% will benefit from migraine surgery.” The word “cure” appears all too often. The following are observations about migraine surgery: Conflict of Interest: The author reports no conflict of interest.
383
384 1. Migraine is a complex syndrome involving genetics, brain chemistry, neuro-inflammation, behavioral aspects, etc, and it is unlikely that a simple surgery would fix all of these factors. 2. Response to Botox (which most of the surgeons use as a guideline) should not necessarily predict a successful surgery; the mechanism of action of Botox for migraines probably involves, among other factors, an antiinflammatory response, not simply via muscle relaxation. 3. The surgery is supposed to be primarily for refractory migraine patients but is being done for those with new onset daily persistent headache (NDPH), post-traumatic headache, occipital neuralgia, and other varied headache syndromes. 4. Migraine and NDPH patients who have not had trials of medications are being operated upon, some of whom have had headaches for less than 1 year, and the patients have not necessarily been under the care of a neurologist or headache specialist. 5. Surgery about the head is not new: migraine patients who have undergone various cosmetic procedures (which are similar to the surgery being promoted) have not reported (in my experience) an improvement in headaches. 6. The disappointment after failed surgery cannot be underestimated. A young man in my practice had NDPH and was 50% improved over 6 months. We could not dissuade him from undergoing the surgery (he was
February 2014 enthralled by the website claims), and after the surgery failed, this patient committed suicide. He was severely depressed, but the disappointment may have been a contributing factor. 7. Adverse events from the surgery should not be minimized; these are sensitized patients, often with allodynia, and cutting structures about the headache may lead to increased headaches or new neuralgia pains. 8. My “anecdotal scorecard” for the surgery results in about a 10% success rate, not the 90% often stated on the surgery websites. We need multicenter trials to evaluate migraine surgery. Without adequate studies, the surgery remains an unproven and experimental procedure. Lawrence Robbins, MD Robbins Headache Clinic – Neurology, Northbrook, IL, USA
REFERENCES 1. Mathew P. A critical evaluation of migraine trigger site deactivation surgery. Headache. 2013. doi:10.1111/head. 12218 2. Guyuron B, Reed D, Kriegler JS, Davis J, Pashmini N, Amini S. A placebo-controlled surgical trial of the treatment of migraine headaches. Plast Reconstr Surg. 2009;124:461468.
Is Orally Inhaled Dihydroergotamine (DHE) Equivalent in Efficacy in Migraine to Intravenous DHE?
explicit statement; but no such scientific study is available. There is also no scientific evidence for the statements on similar efficacy in the 2 other reviews.1,2 In conclusion, orally inhaled DHE is better tolerated than intravenous DHE, but there is no scientific basis for stating that orally inhaled DHE has the same efficacy in migraine as intravenous DHE.
In the last 4 years, headache experts have stated in reviews1-3 that orally inhaled dihydroergotamine (DHE) has similar efficacy as intravenous DHE in the treatment of migraine attacks: In 2010, it was stated by Baron and Tepper that “INH DHE provides an improved tolerability and side effect profile, but similar efficacy to the highly therapeutic IV DHE.”1 In 2012, Silberstein stated in a review of MAP0004 (orally inhaled DHE) that2 “Pulmonary delivery of DHE using MAP0004 provides the expected anti-migraine efficacy of intravenous DHE in a more convenient formulation with fewer systemic side effects. Consequently, MAP0004 should be considered to be a first line therapy for moderate to severe migraine.”2 And in a recent review3 from 2013, Nagy and Rapoport stated: “A new oral DHE inhalation device, Levadex, has been demonstrated to provide similar onset of action and efficacy comparable to intravenous DHE.”3 So we now have 3 largely concordant statements by headache experts1-3 on orally inhaled DHE vs intravenous DHE. One of the essences in these statements is that orally inhaled DHE has fewer systemic adverse events than intravenous DHE.1,2 Based on one comparative, double-blind, pharmacokinetic comparative study4 of orally inhaled and intravenous DHE, it is most likely correct that the orally inhaled form of DHE causes less adverse events than intravenous administration of DHE. The other major point made in all 3 statements is that orally inhaled DHE has similar efficacy as intravenous DHE;1-3 and in one review, it is stated that a “new oral DHE inhalation device, Levadex, has been demonstrated to provide similar onset of action and efficacy comparable to intravenous DHE.”3 The use of the word “demonstrated” would usually imply a scientific basis, in the form of a double-blind, randomized trial, as the basis for such an
Peer Tfelt-Hansen, MD, DMSc From the Department of Neurology, Danish Headache Center, Glostrup Hospital, Glostrup, Denmark
REFERENCES 1. Baron EP, Tepper SJ. Revisiting the role of ergot alkaloids in the treatment of migraine and headache. Headache. 2010;50:1353-1361. 2. Silberstein S. MAP0004: Dihydroergotamine mesylate inhalation aerosol for acute treatment of migraine. Expert Opin Pharmacother. 2012;13:1961-1968. 3. Nagy AJ, Rapoport AM. Update on future headache treatments. Neurol Sci. 2013;34(Suppl. 1):s101-s108. 4. Shrewsbury SB, Cook RO, Taylor G, et al. Safety and pharmacokinetics of dihydroergotamine mesylate administered via a novel (Tempo) inhaler. Headache. 2008;48:355-367.
Migraine Headache Surgery The excellent article by Mathew,“A Critical Evaluation of Migraine Trigger Site Deactivation Surgery,” casts doubt on the data supporting migraine surgery.1,2 Migraine surgery is being promoted by plastic surgeons.A common statement on certain surgery sites states that “of the 60 to 80% of patients who respond to Botox, 90% will benefit from migraine surgery.” The word “cure” appears all too often. The following are observations about migraine surgery: Conflict of Interest: The author reports no conflict of interest.
383
384 1. Migraine is a complex syndrome involving genetics, brain chemistry, neuro-inflammation, behavioral aspects, etc, and it is unlikely that a simple surgery would fix all of these factors. 2. Response to Botox (which most of the surgeons use as a guideline) should not necessarily predict a successful surgery; the mechanism of action of Botox for migraines probably involves, among other factors, an antiinflammatory response, not simply via muscle relaxation. 3. The surgery is supposed to be primarily for refractory migraine patients but is being done for those with new onset daily persistent headache (NDPH), post-traumatic headache, occipital neuralgia, and other varied headache syndromes. 4. Migraine and NDPH patients who have not had trials of medications are being operated upon, some of whom have had headaches for less than 1 year, and the patients have not necessarily been under the care of a neurologist or headache specialist. 5. Surgery about the head is not new: migraine patients who have undergone various cosmetic procedures (which are similar to the surgery being promoted) have not reported (in my experience) an improvement in headaches. 6. The disappointment after failed surgery cannot be underestimated. A young man in my practice had NDPH and was 50% improved over 6 months. We could not dissuade him from undergoing the surgery (he was
February 2014 enthralled by the website claims), and after the surgery failed, this patient committed suicide. He was severely depressed, but the disappointment may have been a contributing factor. 7. Adverse events from the surgery should not be minimized; these are sensitized patients, often with allodynia, and cutting structures about the headache may lead to increased headaches or new neuralgia pains. 8. My “anecdotal scorecard” for the surgery results in about a 10% success rate, not the 90% often stated on the surgery websites. We need multicenter trials to evaluate migraine surgery. Without adequate studies, the surgery remains an unproven and experimental procedure. Lawrence Robbins, MD Robbins Headache Clinic – Neurology, Northbrook, IL, USA
REFERENCES 1. Mathew P. A critical evaluation of migraine trigger site deactivation surgery. Headache. 2013. doi:10.1111/head. 12218 2. Guyuron B, Reed D, Kriegler JS, Davis J, Pashmini N, Amini S. A placebo-controlled surgical trial of the treatment of migraine headaches. Plast Reconstr Surg. 2009;124:461468.
