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Dihydroergotamine: A Review of Formulation Approaches For the Acute Treatment of Migraine

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Abstract

Dihydroergotamine (DHE) was first used to treat migraine in 1945 and is currently included among migraine-specific treatments for moderate-severe migraine. DHE may be administered through several routes of delivery, with efficacy and tolerability varying among formulations. We review DHE formulation approaches for the acute treatment of migraine, reviewing pharmacokinetics/dynamics and comparing clinical response among various formulations. Pharmacokinetic properties vary among DHE formulations, with peak concentration occurring in 6 min with intravenous, 34 min with intramuscular, 56 min with intranasal, 12 min with oral inhalation and 75 min with oral administration. DHE is a potent agonist at serotonin 5-HT1B and 5-HT1D receptors. Adverse effects due to binding to select adrenergic and dopaminergic receptors are significantly less with orally inhaled than intravenous DHE when comparing therapeutically effective doses. Among parenteral formulations (including subcutaneous, intramuscular, intravenous and nasal spray), efficacy is superior with injectable dosing. Nasal spray DHE is generally more effective than placebo, but less effective than sumatriptan. Orally inhaled DHE is likewise more effective than placebo, but there are no head-to-head comparisons with triptans available for review. Adverse effects, particularly nausea, may limit use of parenteral DHE. Nausea is generally less frequent with non-injectable dosing.

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Acknowledgments

Dr. Silberstein is a consultant for MAP Pharmaceuticals. Dr. Kori is an employee of MAP Pharmaceuticals. Funding for this report was provided by MAP Pharmaceuticals. Writing assistance for document preparation was provided by freelance medical writer Dawn A. Marcus, MD.

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Authors and Affiliations

  1. Thomas Jefferson University, Philadelphia, PA, USA

    Stephen D. Silberstein

  2. Clinical Development and Medical Affairs, MAP Pharmaceuticals, Inc., 2400 Bayshore Parkway, Suite 200, Mountain View, CA, 94043-1107, USA

    Shashidhar H. Kori

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  1. Stephen D. Silberstein
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  2. Shashidhar H. Kori
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Correspondence to Shashidhar H. Kori.

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Silberstein, S.D., Kori, S.H. Dihydroergotamine: A Review of Formulation Approaches For the Acute Treatment of Migraine. CNS Drugs 27, 385–394 (2013). https://doi.org/10.1007/s40263-013-0061-2

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