Safe Treatments for Migraine in Pregnancy, Lactation, Menstruation

Migraine is more common in women than in men with a ratio of approximately 3:1.¹ Researchers say that migraine usually begins and becomes more prevalent in women around the time of puberty, which suggests that female sex hormones may play a role in the increased burden of migraine in women. In a study published in Headache, researchers explored the epidemiology and treatment of migraine during pregnancy, lactation, and menstruation.

Migraine in women is most prevalent during reproductive years, with an estimated 21% to 28% of this population experiencing migraine every year.¹ Of these women, up to 80% will continue to have migraines throughout pregnancy, with the highest activity occurring during the first trimester. Migraine with aura tends to present for the first time during pregnancy, as 70% of women who report migraine with aura while pregnant had no history of aura.¹ Additionally, more than half of women with migraine will continue to experience headaches during the first month after delivery.¹

Migraine during pregnancy has been associated with a 1.5-fold to 3-fold increased risk of hypertensive disorders, including preeclampsia.¹ Migraine during pregnancy is also associated with a higher risk for

• preterm birth,
• low birth weight,
• infant hospitalization, and
• febrile seizure.

At this time, monitoring is the only safe known intervention for migraine in pregnancy, as there is no evidence to support any other specific intervention.

First-line treatments for migraine during pregnancy are usually nonpharmacological and focus on healthy lifestyle practices, including quality sleep, regular exercise, nutritional meals, and adequate hydration. Relaxation training and biofeedback are also shown to be effective when practiced consistently during pregnancy, and may help prevent migraine.

Many pharmacological treatments for migraine during pregnancy have been poorly studied; yet, migraine during pregnancy must be properly treated to reduce risks such as dehydration and electrolyte imbalances, which may occur on behalf of migraine-induced vomiting.

Preferred pharmacological treatments for migraine in pregnancy include acetaminophen, diphenhydramine, lidocaine SQ, metoclopramide, and nonsteroidal anti-inflammatory drugs — the latter of which can be safely used during the second trimester only.¹ Approved second-line treatments include triptans, butalbital, ondansetron, short-acting prednisone, prochlorperazine, and promethazine. Medications that should be avoided to treat migraine in pregnancy include aspirin, opiates, indomethacin, and ergots.

Prevention of migraine during pregnancy may be best achieved with propranolol. Researchers say that results from observational studies show that when used to treat migraine in early pregnancy, propranolol was associated with a small increase in the risk for intrauterine growth retardation, small placenta, and congenital abnormalities. Safe choices for second-line treatment include cyclobenzaprine and memantine. Medications that should always be avoided when preventing migraine in pregnancy include feverfew and valproic acid, due to higher risks for spontaneous abortion and fetal malformation.

Researchers note there are 2 prospective studies that have evaluated whether breastfeeding has an effect on the incidence of migraine following delivery.¹ Results from a study involving 208 women showed that breastfeeding had no effect on migraine, while results from a second study revealed that breastfeeding had protective effects against migraine.

As with migraine in pregnancy, there is little evidence on the safety of migraine medications during breastfeeding; however, the little evidence that does exist suggests there are more options for treatment during lactation than during pregnancy. Acetaminophen, lidocaine SQ, and ibuprofen are preferred first-line treatments for migraine in lactation, and are compatible with breastfeeding. Second-line treatments include diphenhydramine, metoclopramide, ondansetron, and prednisone, while medications that should always be avoided include ergots and opiates.

Researchers recommend that women reduce their infants’ exposure to migraine medications by pumping and discarding breast milk once following medication use, or by using the medication immediately before an anticipated long stretch between feedings. Second-line treatments may not require these same precautions in healthy infants over the age of 6 to 8 weeks, as long as medications are being used at normal doses.

Preventive medications for migraine during lactation include verapamil, propranolol, magnesium, and sodium valproate — all of which are compatible with breastfeeding. Results from a 2013 study published in Headache showed that although valproate is considered high-risk during pregnancy, this medication is safer to use while breastfeeding due to low concentrations in breast milk.²

Amitriptyline may be used as a second-line treatment, though reports have linked this medication to sedation in infants—a risk that generally decreases as the infant grows older. Medications that should always be avoided for migraine prevention in lactation due to lack of evidence include candesartan, calcitonin gene-related peptide monoclonal antibodies, coenzyme Q10, feverfew, lisinopril, memantine, and onabotulinum toxin A.

Migraines are found more likely to occur in women during menstruation than during any other time. Migraine attacks that occur anywhere from 2 days before menstruation to 3 days after menstruation begins is diagnosed as menstrual migraine.¹ Migraine attacks that occur only during menstruation are diagnosed as pure menstrual migraine, while attacks that may also occur at other times of the month are generally diagnosed as menstrual-related migraine.

Pure menstrual migraine occurs in approximately 8% of all women with migraine, while menstrual-related migraine occurs in 13% of women with migraine.¹ Researchers cite fluctuations in female sex hormones as the clear underlying cause for peak in headache activity during menstruation, though it remains unclear whether migraine attacks are directly caused by lower estrogen, mechanisms surrounding fluctuations in prostaglandin, serotonin, and dopamine, or a combination of these and/or other mechanisms.

Menstrual migraines tend to respond well to triptans and do not persist following initiation of treatment. If triptans are ineffective when used on their own or with nonsteroidal anti-inflammatory drugs and antiemetics, short-term prevention using scheduled dosing of long-acting triptans may be effective at preventing menstrual migraine. Additionally, results from a 2017 study published in the Journal of Headache and Pain showed that women with menstrual-related migraine who received treatment from both a neurologist and gynecologist experienced significant improvements in migraine compared with women who were treated only by a neurologist.³

Hormonal treatment strategies have also been found effective at preventing menstrual migraine, and aim to limit the decline of estrogen during menstruation to reduce migraine. One hormone intervention supplements low-dose estrogen in the form of 1.5 mg estradiol gel, while the other intervention suppresses hormonal cycling using continuous or extended-duration monophasic combined hormonal contraceptives. Researchers note that results from trials that used these interventions showed they were highly effective at reducing migraine burden during menstruation.¹

Though migraine that occurs in pregnancy, lactation, and menstruation may be viewed as special situations in migraine treatment, most women with migraine are likely to experience at least 1 of these situations during their lifetime.¹ At this time, more research is needed to identify safe migraine treatments during pregnancy and lactation; however, women with migraine should understand and know that there are a wide range of available and pharmacologic and nonpharmacologic treatment options.

References

1. Burch R. Epidemiology and treatment of menstrual migraine and migraine during pregnancy and lactation: a narrative review [published online October 3, 2019]. Headache. doi: 10.1111/head.13665

2. 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(4):614–627.

3. Witteveen H, van den Berg P, Vermeulen G. Treatment of menstrual migraine; multidisciplinary or mono-disciplinary approach. J Headache Pain. 2017;18(1):45.