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 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.
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.
Buy single article
Instant access to the full article PDF.
Price includes VAT for USA
Subscribe to journal
Immediate online access to all issues from 2019. Subscription will auto renew annually.
This is the net price. Taxes to be calculated in checkout.
Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
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.
Marcus DA. Interrelationships of neurochemicals, estrogen, and recurring headache. Pain. 1995;62:129–39.
Marcus DA, Scharff L, Turk D. Longitudinal prospective study of headache during pregnancy and postpartum. J Head Face Pain. 1999;39:625–32.
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.
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.
Maggioni F, Alessi C, Maggino T, Zanchin G. Headache during pregnancy. Cephalalgia. 1997;17:765–9.
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.
•• 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.
• 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.
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.
Scharff L, Marcus DA, Turk DC. Headache during pregnancy and in the postpartum: a prospective study. Headache. 1997;37:203–10.
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.
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.
Whyte J. FDA implements new labeling for medications used during pregnancy and lactation. Am Fam Physician. 2016;94:12–3.
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.
Glistrap LC, Little BB. In: Gilstrap LC, Little BB, editors. Drugs and pregnancy. 2nd ed. New York: Chapman & Hall; 1998.
•• 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.
Hotham N, Hotham E. Drugs in breastfeeding. Aust Prescr. 2015;38:156–9.
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.
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.
Welch KMA, Ramadan NM. Mitochondria, magnesium and migraine. J Neurol Sci. 1995;134:9–14.
Schoenen J, Jacquy J, Lenaerts M. Effectiveness of high-dose riboflavin in migraine prophylaxis. A randomized controlled trial. Neurology. 1998;50:466–70.
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.
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.
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.
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.
Teigen L, Boes CJ. An evidence-based review of oral magnesium supplementation in the preventive treatment of migraine. Cephalalgia. 2015;35:912–22.
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.
Makrides M, Crosby DD, Bain E, Crowther CA. Magnesium supplementation in pregnancy. Cochrane Database Syst Rev. 2014.
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.
Meadow R. Anticonvulsants in pregnancy. Arch Dis Child. 1991;66:62–5.
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.
Veiby G, Engelsen BA, Gilhus NE. Early child development and exposure to antiepileptic drugs prenatally and through breastfeeding. JAMA Neurol. 2013;70:1367–74.
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
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.
Abalos E, Duley L, Steyn DW. Antihypertensive drug therapy for mild to moderate hypertension during pregnancy. Cochrane Database Syst Rev. 2014;6:CD002252.
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
Miller LJ. Psychopharmacology during pregnancy. Prim Care Update Ob Gyns. 1996;3:79–86.
Quan A. Fetopathy associated with exposure to angiotensin converting enzyme inhibitors and angiotensin receptor antagonists. Early Hum Dev. 2006;82:23–8.
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.
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.
• 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.
• 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.
• 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.
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.
Namenda XR (memantine hydrochloride) capsules label. [cited 2018 Jul 23]; Available from: www.fda.gov/medwatch.
•• 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.
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.
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.
•• 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.
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.
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.
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.
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.
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.
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.
This article is part of the Topical Collection on Episodic Migraine
About this article
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
- Drug safety