Current Treatment Options in Neurology

, Volume 14, Issue 1, pp 27–35 | Cite as

Use of Dopamine Antagonists in Treatment of Migraine

Headache (JR Couch, Section Editor)

Opinion statement

Dopamine antagonists are indicated for treatment of nausea or psychosis and have an established role in the treatment of migraine. Neuroleptics, including antipsychotics, act as antagonists at the dopamine D2 receptor type. These medications also have variable activity as antihistamines and anticholinergics, and they block alpha-adrenergic and some serotonin receptor types, but their actions on dopamine are likely the reason for their efficacy in treating nausea, psychosis, and acute migraine. Neuroleptics are first-line agents in the emergency room setting for migraine, especially for patients with nausea and vomiting. In the setting of a clear prodrome, antiemetics may prevent migraine when taken before an attack. They are also indicated in clinical situations such as patients who are pregnant or have contraindications to migraine-specific medications or NSAIDs. Recent developments suggest that dopamine is particularly important in chronic pain, and we most commonly use neuroleptic medications in the treatment of status migrainosus or medication-overuse headache. Clinicians may avoid dopamine antagonists because of unfamiliarity and a lack of large, controlled clinical trials. Their use requires special care to avoid adverse events such as sedation, akathisia or dystonic reactions, neuroleptic malignant syndrome, or movement disorders with long-term use. Some newer atypical neuroleptic agents appear promising for both acute and prophylactic migraine treatment with a lower risk of adverse events.


Dopamine Migraine Treatment Prophylaxis Neuroleptics Dopamine antagonists Status migrainosus Prodrome Adverse events Efficacy Nausea 

References and Recommended Reading

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    Diamond S, Bigal ME, Silberstein S, Loder E, Reed M, Lipton RB. Patterns of diagnosis and acute and preventive treatment for migraine in the United States: results from the American Migraine Prevalence and Prevention Study. Headache. 2001;41:646.PubMedCrossRefGoogle Scholar
  2. 2.
    Dodick D, Lipton RB, Martin V, Papademetriou V, Rosamond W, Maassen Van Den Brink A, et al. Triptan cardiovascular safety expert panel. Consensus statement: cardiovascular safety profile of triptans (5-HT agonists) in the acute treatment of migraine. Headache. 2004;44(5):414–25.PubMedCrossRefGoogle Scholar
  3. 3.•
    Bigal ME, Lipton RB. Overuse of acute migraine medications and migraine chronification. Curr Pain Headache Rep. 2009;13(4):301–7.PubMedCrossRefGoogle Scholar
  4. 4.
    Peroutka SJ, Wilhoit T, Jones K. Clinical susceptibility to migraine with aura is modified by dopamine D2 receptor (DRD2) NcoI alleles. Neurology. 1997;49:201–6.PubMedGoogle Scholar
  5. 5.
    Fernandez F, Lea RA, Colson NJ, Bellis C, Quinlan S, Griffiths LR. Association between a 19 bp deletion polymorphism at the dopamine beta-hydroxylase (DBH) locus and migraine with aura. J Neurol Sci. 2006;251:118–23.PubMedCrossRefGoogle Scholar
  6. 6.
    Cevoli S, Mochi M, Scapoli C, Marzocchi N, Pierangeli G, Pini LA, et al. A genetic association study of dopamine metabolism-related genes and chronic headache with drug abuse. Eur J Neurol. 2006;13:1009–13.PubMedCrossRefGoogle Scholar
  7. 7.
    Del Zompo M, Lai M, Loi V, Pisano MR. Dopamine hypersensitivity in migraine: role in apomorphine syncope. Headache. 1995;35:222–4.PubMedCrossRefGoogle Scholar
  8. 8.•
    Borsook D, Upadhyay J, Chudler EH, Becerra L. A key role of the basal ganglia in pain and analgesia—insights gained through human functional imaging. Mol Pain. 2010;6:27.PubMedCrossRefGoogle Scholar
  9. 9.
    Chappell AS, Bay JM, Botzum GD, Cohen ML. Zatosetron, a 5-HT3 receptor antagonist in a multicenter trial for acute migraine. Neuropharmacology. 1994;33(3–4):509–13.PubMedCrossRefGoogle Scholar
  10. 10.
    Damier P. Drug-induced dyskinesias. Curr Opin Neurol. 2009;22(4):394–9.PubMedCrossRefGoogle Scholar
  11. 11.
    Jones J, Sklar D, Dougherty J, White W. Randomized double-blind trial of intravenous prochlorperazine for the treatment of acute headache. JAMA. 1989;261:1174–6.PubMedCrossRefGoogle Scholar
  12. 12.
    Jones J, Pack S, Chun E. Intramuscular prochlorperazine versus metoclopramide as single-agent therapy for the treatment of acute migraine headache. Am J Emerg Med. 1996;14:262–4.PubMedCrossRefGoogle Scholar
  13. 13.
    Ginder S, Oatman B, Pollack M. A prospective study of i.v. magnesium and i.v. prochlorperazine in the treatment of headaches. J Emerg Med. 2000;18:311–5.PubMedCrossRefGoogle Scholar
  14. 14.
    Seim MB, March JA, Dunn KA. Intravenous ketorolac vs intravenous prochlorperazine for the treatment of migraine headaches. Acad Emerg Med. 1998;5:573–6.PubMedCrossRefGoogle Scholar
  15. 15.
    Brousseau DC, Duffy SJ, Anderson AC, Linakis JG. Treatment of pediatric migraine headaches: a randomized, double-blind trial of prochlorperazine versus ketorolac. Ann Emerg Med. 2004;43(2):256–62.PubMedCrossRefGoogle Scholar
  16. 16.
    Tietjen GE, Athanas K, Utley C, Herial NA, Khuder SA. The combination of naratriptan and prochlorperazine in migraine treatment. Headache. 2005;45(6):751–3.PubMedCrossRefGoogle Scholar
  17. 17.•
    Kirthi V, Derry S, Moore RA, McQuay HJ. Aspirin with or without an antiemetic for acute migraine headaches in adults. Cochrane Database Syst Rev. 2010;14:1–44.Google Scholar
  18. 18.
    Colman I, Brown MD, Innes GD, Grafstein E, Roberts TE, Rowe BH. Parenteral metoclopramide for acute migraine: meta-analysis of randomised controlled trials. BMJ. 2004;329(7479):1369–73.PubMedCrossRefGoogle Scholar
  19. 19.
    Klapper JA, Stanton JS. Ketorolac versus DHE and metoclopramide in the treatment of migraine headaches. Headache. 1991;31:523–4.PubMedCrossRefGoogle Scholar
  20. 20.••
    Friedman BW, Mulvey L, Esses D, Solorzano C, Paternoster J, Lipton RB, Gallagher EJ. Metoclopramide for acute migraine: a dose-finding randomized clinical trial. Ann Emerg Med. 2011;57(5):475–482e1.PubMedCrossRefGoogle Scholar
  21. 21.
    Bigal ME, Bordini CA, Speciali JG. Intravenous chlorpromazine in the emergency department treatment of migraines: a randomized controlled trial. J Emerg Med. 2002;23:141–8.PubMedCrossRefGoogle Scholar
  22. 22.
    Bell R, Montoya D, Shuaib A, Lee MA. A comparative trial of three agents in the treatment of acute migraine headache. Ann Emerg Med. 1990;19:1079–82.PubMedCrossRefGoogle Scholar
  23. 23.
    Richman PB, Allegra J, Eskin B, et al. A randomized clinical trial to assess the efficacy of intramuscular droperidol for the treatment of acute migraine headache. Am J Emerg Med. 2002;20:39–42.PubMedCrossRefGoogle Scholar
  24. 24.
    Silberstein SD, Young WB, Mendizabal JE, Rothrock JF, Alam AS. Acute migraine treatment with droperidol: a randomized, double-blind, placebo-controlled trial. Neurology. 2003;60(2):315–21.PubMedGoogle Scholar
  25. 25.
    Honkaniemi J, Liimatainen S, Rainesalo S, Sulavuori S. Haloperidol in the acute treatment of migraine: a randomized, double-blinded, placebo-controlled study. Headache. 2006;46:781–7.PubMedCrossRefGoogle Scholar
  26. 26.
    Kelman L. The premonitory symptoms (prodrome): a tertiary care study of 893 migraineurs. Headache. 2004;44(9):865–72.PubMedCrossRefGoogle Scholar
  27. 27.
    Waelkens J. Domperidone in the prevention of complete classical migraine. Br Med J (Clin Res Ed). 1982;284(6320):944.CrossRefGoogle Scholar
  28. 28.
    Waelkens J. Dopamine blockade with domperidone: bridge between prophylactic and abortive treatment of migraine? A dose-finding study. Cephalalgia. 1984;4:85–90.PubMedCrossRefGoogle Scholar
  29. 29.
    Rozen TD. Migraine prodrome: a nose on a face. Lancet. 2004;363:517.PubMedCrossRefGoogle Scholar
  30. 30.
    Bisol LW, Brunstein MG, Ottoni GL, Ramos FL, Borba DL, Daltio CS, et al. Is flunarizine a long-acting oral atypical antipsychotic? A randomized clinical trial versus haloperidol for the treatment of schizophrenia. J Clin Psychiatry. 2008;69(10):1572–9.PubMedCrossRefGoogle Scholar
  31. 31.
    LaPorta LD. Relief from migraine headache with aripiprazole treatment. Headache. 2007;47(6):922–6.PubMedCrossRefGoogle Scholar
  32. 32.
    Cahill CM, Hardiman O, Murphy KC. Treatment of refractory chronic daily headache with the atypical antipsychotic ziprasidone—a case series. Cephalalgia. 2005;25:822–6.PubMedCrossRefGoogle Scholar
  33. 33.
    Silberstein SD, Peres MF, Hopkins MM, et al. Olanzapine in the treatment of refractory migraine and chronic daily headache. Headache. 2002;42:515–8.PubMedCrossRefGoogle Scholar
  34. 34.
    Siow HC, Young WB, Silberstein SD. Neuroleptics in headache. Headache. 2005;45:358–71.PubMedCrossRefGoogle Scholar
  35. 35.•
    Krymchantowski AV, Jevoux C, Moreira PF. An open pilot study assessing the benefits of quetiapine for the prevention of migraine refractory to the combination of atenolol, nortriptyline, and flunarizine. Pain Med. 2010;11(1):48–52.PubMedCrossRefGoogle Scholar
  36. 36.
    Trottier ED, Bailey B, Dauphin-Pierre S, Gravel J. Clinical outcomes of children treated with intravenous prochlorperazine for migraine in a pediatric emergency department. J Emerg Med. 2010;39(2):166–73.PubMedCrossRefGoogle Scholar
  37. 37.
    Trottier ED, Bailey B, Lucas N, Lortie A. Prochlorperazine in children with migraine: a look at its effectiveness and rate of akathisia. Am J Emerg Med. 2011 Feb 4. doi:10.1016/j.ajem.2010.12.020.

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  1. 1.Department of NeurologyThomas Jefferson University, Jefferson Headache CenterPhiladelphiaUSA

Personalised recommendations