Unique Populations with Episodic Migraine: Pregnant and Lactating Women

Abstract

Purpose of Review

Migraine is a disabling and prevalent neurological disease, commonly affecting women during their reproductive years. It is crucial for providers to be able to adequately counsel women who are pregnant, planning pregnancy, or nursing, regarding preventive and abortive treatment options for episodic migraine. This review will discuss (1) the expected course of migraine during pregnancy and the post-partum period, (2) recommended preventive therapies for migraine during pregnancy and lactation, and (3) recommended abortive medications for migraine during pregnancy and lactation.

Recent Findings

Recent research has indicated safety for triptan use during pregnancy and ibuprofen use during the first trimester of pregnancy. Considerations for use of emerging migraine-preventive treatment, such as non-invasive neurostimulators, are discussed.

Summary

For clinical decision-making and patient counseling, it is important to understand both the limitations in determining teratogenic effects in humans and the principles affecting medication transmission from mother to breast milk.

This is a preview of subscription content, log in to check access.

References

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

  1. 1.

    Lipton RB, Stewart WF, Diamond S, Diamond ML, Reed M. Prevalence and burden of migraine in the United States data from the American migraine study II. Headache. 2001;41:646–57.

    CAS  Article  Google Scholar 

  2. 2.

    Marcus DA. Interrelationships of neurochemicals, estrogen, and recurring headache. Pain. 1995;62:129–39.

    CAS  Article  Google Scholar 

  3. 3.

    Marcus DA, Scharff L, Turk D. Longitudinal prospective study of headache during pregnancy and postpartum. J Head Face Pain. 1999;39:625–32.

    CAS  Article  Google Scholar 

  4. 4.

    Sances G, Granella F, Nappi RE, Fignon A, Ghiotto N, Polatti F, et al. Course of migraine during pregnancy and postpartum: a prospective study. Cephalalgia. 2003;23:197–205.

    CAS  Article  Google Scholar 

  5. 5.

    Serva WA, Serva VM, de Fátima Costa Caminha M, Figueiroa JN, Albuquerque EC, Serva GB, et al. Course of migraine during pregnancy among migraine sufferers before pregnancy. Arq Neuropsiquiatr. 2011;69:613–9.

    Article  Google Scholar 

  6. 6.

    Maggioni F, Alessi C, Maggino T, Zanchin G. Headache during pregnancy. Cephalalgia. 1997;17:765–9.

    CAS  Article  Google Scholar 

  7. 7.

    Kvisvik EV, Stovner LJ, Helde G, Bovim G, Linde M. Headache and migraine during pregnancy and puerperium: the MIGRA-study. J Headache Pain. 2011;12:443–51.

    CAS  Article  Google Scholar 

  8. 8.

    •• Spielmann K, Kayser A, Beck E, Meister R, Schaefer C. Pregnancy outcome after anti-migraine triptan use: a prospective observational cohort study. Cephalalgia. 2018;38:1081–92. Importance: Recent study evaluating the teratogenicity of triptans.

    Article  Google Scholar 

  9. 9.

    • Grossman TB, Robbins MS, Govindappagari S, Dayal AK. Delivery outcomes of patients with acute migraine in pregnancy: a retrospective study. Headache. 2017;57:605–11. Importance: Novel study on pregnancy outcomes for women seeking acute treatment for migraine during pregnancy.

  10. 10.

    Goldszmidt E, Kern R, Chaput A, Macarthur A. The incidence and etiology of postpartum headaches: a prospective cohort study. Can J Anesth. 2005;52:971–7.

    Article  Google Scholar 

  11. 11.

    Scharff L, Marcus DA, Turk DC. Headache during pregnancy and in the postpartum: a prospective study. Headache. 1997;37:203–10.

    CAS  Article  Google Scholar 

  12. 12.

    Addis A, Sharabi S, Bonati M. Risk classification systems for drug use during pregnancy: are they a reliable source of information? Drug Saf. 2000;23:245–53.

    CAS  Article  Google Scholar 

  13. 13.

    Sannerstedt R, Lundborg P, Danielsson BR, Kihlström I, Alván G, Prame B, et al. Drugs during pregnancy: an issue of risk classification and information to prescribers. Drug Saf. 1996;14:69–77.

    CAS  Article  Google Scholar 

  14. 14.

    Whyte J. FDA implements new labeling for medications used during pregnancy and lactation. Am Fam Physician. 2016;94:12–3.

    PubMed  Google Scholar 

  15. 15.

    Baird PA, Anderson TW, Newcombe HB, Lowry RB. Genetic disorders in children and young adults: a population study. Am J Hum Genet. 1988;42:677–93.

    CAS  PubMed  PubMed Central  Google Scholar 

  16. 16.

    Glistrap LC, Little BB. In: Gilstrap LC, Little BB, editors. Drugs and pregnancy. 2nd ed. New York: Chapman & Hall; 1998.

    Google Scholar 

  17. 17.

    •• Hale T, Rowe HE. Medications and mothers’ milk. 17th ed. Danvers, MA: Springer Publishing Company, LLC; 2017. Importance: Comprehensive resource for assessing lactation risk for medications.

  18. 18.

    Hotham N, Hotham E. Drugs in breastfeeding. Aust Prescr. 2015;38:156–9.

    Article  Google Scholar 

  19. 19.

    Airola G, Allais G, Gabellari IC, Rolando S, Mana O, Benedetto C. Non-pharmacological management of migraine during pregnancy. Neurol Sci. 2010;31:63–5.

    Article  Google Scholar 

  20. 20.

    Welch KM, Levine SR, D’Andrea G, Schultz LR, Helpern JA. Preliminary observations on brain energy metabolism in migraine studied by in vivo phosphorus 31 NMR spectroscopy. Neurology. 1989;39:538–41.

    CAS  Article  Google Scholar 

  21. 21.

    Welch KMA, Ramadan NM. Mitochondria, magnesium and migraine. J Neurol Sci. 1995;134:9–14.

    CAS  Article  Google Scholar 

  22. 22.

    Schoenen J, Jacquy J, Lenaerts M. Effectiveness of high-dose riboflavin in migraine prophylaxis. A randomized controlled trial. Neurology. 1998;50:466–70.

    CAS  Article  Google Scholar 

  23. 23.

    Shults CW, Beal MF, Fontaine D, Nakano K, Haas RH, Magis D, et al. Absorption, tolerability, and effects on mitochondrial activity of oral coenzyme Q10 in parkinsonian patients. Neurology. 1998;50:793–5.

    CAS  Article  Google Scholar 

  24. 24.

    Teran E, Hernandez I, Nieto B, Tavara R, Ocampo JE, Calle A. Coenzyme Q10 supplementation during pregnancy reduces the risk of pre-eclampsia. Int J Gynecol Obstet Wiley-Blackwell. 2009;105:43–5.

    CAS  Article  Google Scholar 

  25. 25.

    Ma AG, Schouten EG, Zhang FZ, Kok FJ, Yang F, Jiang DC, et al. Retinol and riboflavin supplementation decreases the prevalence of anemia in Chinese pregnant women taking Iron and folic acid supplements. J Nutr Oxford University Press. 2008;138:1946–50.

    CAS  Google Scholar 

  26. 26.

    Ma AG, Schouten EG, Ye Sun Y, Yang F, Xia Han X, Zhi Zhang F, et al. Supplementation of iron alone and combined with vitamins improves haematological status, erythrocyte membrane fluidity and oxidative stress in anaemic pregnant women. Br J Nutr. 2010;104:1655–61.

    CAS  Article  Google Scholar 

  27. 27.

    Teigen L, Boes CJ. An evidence-based review of oral magnesium supplementation in the preventive treatment of migraine. Cephalalgia. 2015;35:912–22.

    Article  Google Scholar 

  28. 28.

    Pfaffenrath V, Wessely P, Meyer C, Isler HR, Evers S, Grotemeyer KH, et al. Magnesium in the prophylaxis of migraine—a double-blind placebo-controlled study. Cephalalgia. 1996;16:436–40.

    CAS  Article  Google Scholar 

  29. 29.

    Makrides M, Crosby DD, Bain E, Crowther CA. Magnesium supplementation in pregnancy. Cochrane Database Syst Rev. 2014.

  30. 30.

    Silberstein SD, Holland S, Freitag F, Dodick DW, Argoff C, Ashman E, et al. Evidence-based guideline update: pharmacologic treatment for episodic migraine prevention in adults: table 1. Neurology. 2012;78:1337–45.

    CAS  Article  Google Scholar 

  31. 31.

    Meadow R. Anticonvulsants in pregnancy. Arch Dis Child. 1991;66:62–5.

    CAS  Article  Google Scholar 

  32. 32.

    Kelly TE, Rein M, Edwards P. Teratogenicity of anticonvulsant drugs. IV: the association of clefting and epilepsy. Am J Med Genet. 1984;19:451–8.

    CAS  Article  Google Scholar 

  33. 33.

    Veiby G, Engelsen BA, Gilhus NE. Early child development and exposure to antiepileptic drugs prenatally and through breastfeeding. JAMA Neurol. 2013;70:1367–74.

    Article  Google Scholar 

  34. 34.

    Meador KJ, Baker GA, Browning N, Cohen MJ, Bromley RL, Clayton-Smith J, et al. Breastfeeding in children of women taking antiepileptic drugs. JAMA Pediatr [Internet]. 2014 [cited 2018 May 19];168:729. Available from: http://www.ncbi.nlm.nih.gov/pubmed/24934501

  35. 35.

    Bayliss H, Churchill D, Beevers M, Beevers DG. Anti-hypertensive drugs in pregnancy and fetal growth: evidence for “pharmacological programming” in the first trimester? Hypertens Pregnancy. 2002;21:161–74.

    CAS  Article  Google Scholar 

  36. 36.

    Abalos E, Duley L, Steyn DW. Antihypertensive drug therapy for mild to moderate hypertension during pregnancy. Cochrane Database Syst Rev. 2014;6:CD002252.

    Google Scholar 

  37. 37.

    Lusskin SI, Khan SJ, Ernst C, Habib S, Fersh ME, Albertini ES. Pharmacotherapy for perinatal depression. Clin Obstet Gynecol [Internet]. 2018;00:1. Available from: https://doi.org/10.1097/GRF.0000000000000365

  38. 38.

    Miller LJ. Psychopharmacology during pregnancy. Prim Care Update Ob Gyns. 1996;3:79–86.

    Article  Google Scholar 

  39. 39.

    Quan A. Fetopathy associated with exposure to angiotensin converting enzyme inhibitors and angiotensin receptor antagonists. Early Hum Dev. 2006;82:23–8.

    CAS  Article  Google Scholar 

  40. 40.

    Horvath JS, Phippard A, Korda A, Henderson-Smart DJ, Child A, Tiller DJ. Clonidine hydrochloride—a safe and effective antihypertensive agent in pregnancy. Obstet Gynecol. 1985;66:634–8.

    CAS  PubMed  Google Scholar 

  41. 41.

    Yallampalli C, Chauhan M, Thota CS, Kondapaka S, Wimalawansa SJ. Calcitonin gene-related peptide in pregnancy and its emerging receptor heterogeneity. Trends Endocrinol Metab. 2002;13:263–9.

    CAS  Article  Google Scholar 

  42. 42.

    • Miller S, Sinclair AJ, Davies B, Matharu M. Neurostimulation in the treatment of primary headaches. Pract Neurol. 2016;16:362–75. Importance: Further reading on neurostimulation options for migraine treatment.

    Article  Google Scholar 

  43. 43.

    • Bhola R, Kinsella E, Giffin N, Lipscombe S, Ahmed F, Weatherall M, et al. Single-pulse transcranial magnetic stimulation (sTMS) for the acute treatment of migraine: evaluation of outcome data for the UK post market pilot program. J Headache Pain. 2015;16:535. Importance: Further reading on transcranial magnetic stimulation for migraine acute treatment.

  44. 44.

    • Judkins A, Johnson RL, Murray ST, Yellon SM, Wilson CG. Vagus nerve stimulation in pregnant rats and effects on inflammatory markers in the brainstem of neonates. Pediatr Res. 2018;83:514–9. Importance: Further reading on vagus nerve stimulation for migraine treatment during pregnancy.

    Article  Google Scholar 

  45. 45.

    Noruzzadeh R, Modabbernia A, Aghamollaii V, Ghaffarpour M, Harirchian MH, Salahi S, et al. Memantine for prophylactic treatment of migraine without aura: a randomized double-blind placebo-controlled study. Headache J Head Face Pain. 2016;56:95–103.

    Article  Google Scholar 

  46. 46.

    Namenda XR (memantine hydrochloride) capsules label. [cited 2018 Jul 23]; Available from: www.fda.gov/medwatch.

  47. 47.

    •• Dathe K, Fietz A-K, Pritchard LW, Padberg S, Hultzsch S, Meixner K, et al. No evidence of adverse pregnancy outcome after exposure to ibuprofen in the 1st trimester—evaluation of the national embryotox cohort. Reprod Toxicol. 2018;79:32–8. Importance: Recent study evaluating the teratogenicity of ibuprofen use during the first trimester.

    CAS  Article  Google Scholar 

  48. 48.

    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;329:1369–73.

    CAS  Article  Google Scholar 

  49. 49.

    Childress KS, Dothager C, Gavard J, Lebovitz S, Mostello D. Metoclopramide and diphenhydramine: a randomized controlled trial of a treatment for headache in pregnancy when acetaminophen alone is ineffective (MAD headache study). Am J Obstet Gynecol [Internet]. 2014;210:S277. https://doi.org/10.1016/j.ajog.2013.10.597.

    Article  Google Scholar 

  50. 50.

    •• Hutchinson S, Marmura MJ, Calhoun A, Lucas S, Silberstein S, Peterlin BL. Use of common migraine treatments in breast-feeding women: a summary of recommendations. Headache. 2013;53:614–27 Importance: Comprehensive resource for assessing lactation risk for medications.

    Article  Google Scholar 

  51. 51.

    Westergren T, Hjelmeland K, Kristoffersen B, Johannessen SI, Kalikstad B. Probable topiramate-induced diarrhea in a 2-month-old breast-fed child—a case report. Epilepsy Behav Case Reports. 2014;2:22–3.

    Article  Google Scholar 

  52. 52.

    Stahl MM, Neiderud J, Vinge E. Thrombocytopenic purpura and anemia in a breast-fed infant whose mother was treated with valproic acid. J Pediatr. 1997;130:1001–3.

    CAS  Article  Google Scholar 

  53. 53.

    Ilett KF, Kristensen JH, Hackett LP, Paech M, Kohan R, Rampono J. Distribution of venlafaxine and its O-desmethyl metabolite in human milk and their effects in breastfed infants. Br J Clin Pharmacol. 2002;53:17–22.

    CAS  Article  Google Scholar 

  54. 54.

    Townsend RJ, Benedetti TJ, Erickson SH, Cengiz C, Gillespie WR, Gschwend J, et al. Excretion of ibuprofen into breast milk. Am J Obstet Gynecol. 1984;149:184–6.

    CAS  Article  Google Scholar 

  55. 55.

    Ito S, Blajchman A, Stephenson M, Eliopoulos C, Koren G. Prospective follow-up of adverse reactions in breast-fed infants exposed to maternal medication. Am J Obstet Gynecol. 1993;168:1393–9.

    CAS  Article  Google Scholar 

Download references

Author information

Affiliations

Authors

Corresponding author

Correspondence to Simy K. Parikh.

Ethics declarations

Conflict of Interest

Simy K. Parikh declares no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Additional information

This article is part of the Topical Collection on Episodic Migraine

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Parikh, S.K. Unique Populations with Episodic Migraine: Pregnant and Lactating Women. Curr Pain Headache Rep 22, 80 (2018). https://doi.org/10.1007/s11916-018-0737-x

Download citation

Keywords

  • Pregnancy
  • Migraine
  • Teratogenicity
  • Lactation
  • Drug safety