Migraine Treatment in Pregnancy

Abstract and Introduction

Abstract

Objective: The objective of this study was to assess women's healthcare providers' treatment practices for pregnant women with migraine.

Background: Migraine is associated with several maternal and fetal complications during pregnancy, including preeclampsia and preterm birth. Migraine treatment during pregnancy can present significant challenges due to lack of controlled clinical trials and risks associated with specific medications.

Methods: Women's healthcare providers were queried regarding practice patterns and comfort with use of acute and preventive migraine treatments during pregnancy. The survey was distributed online.

Results: The survey was completed by 92 women's healthcare providers (response rate 22.9% [92/402]), with most specializing in general obstetrics and gynecology (91% [83/92]). Approximately one-fourth (26% [24/92]) of respondents indicated they counseled women on migraine treatment in pregnancy as early as before pregnancy contemplation, while over one-third (35% [32/92]) counseled on migraine treatment once the patient became pregnant. The majority of respondents reported feeling somewhat or very comfortable with recommending (63% [58/92]) or continuing (64% [59/92]) acute treatments for pregnant patients with migraine, with highest comfort levels for acetaminophen (100% [92/92] for prescribing or continuing) and caffeine (94% [85/90] prescribing, 91% [82/90] continuing). Higher levels of discomfort were reported with triptans (88% [80/91] rarely or never prescribe during pregnancy). Survey respondents felt less comfortable with recommending preventive migraine treatments to pregnant patients (40% [37/92] somewhat or very comfortable), compared with a higher comfort level with continuing preventive medications (63% [58/92] somewhat or very comfortable). Highest comfort levels were reported with use of magnesium (69% [63/91] comfortable prescribing, 82% [75/92] comfortable continuing) and non-pharmacologic approaches (70% [62/89] comfortable prescribing, 84% [75/89] comfortable continuing). Nearly 40% (35/92) of respondents reported that they typically refer to neurologists or headache specialists for migraine treatment during pregnancy.

Conclusion: This survey of women's healthcare providers revealed varying levels of comfort regarding migraine management during pregnancy, and highlights the need for additional education regarding migraine treatment safety data during pregnancy.

Introduction

Migraine is three times more likely to occur in women than in men in the United States, and the peak of migraine prevalence for women occurs during the reproductive years.^[1–3] Previous studies suggest an estimated 21%–28% of women of reproductive age experience migraine annually, and up to 80% of these women will continue to have migraine at some phase of pregnancy.^[4–6] Approximately half of women report improvement in migraine symptoms by the end of the first trimester, and these reductions in frequency and severity may rise to nearly 80% in the second trimester.^[7] However, other data suggest that over 60% of women may not have headache improvement during pregnancy.^[8] There appear to be differences in migraine relief based on different migraine subtypes, as those with preexisting menstrual migraine may experience more relief during pregnancy due to increasing levels of estrogen,^[9] while women with migraine with aura are less likely to improve during pregnancy.^[10] For some women, migraine may occur for the first time during pregnancy, and this is more likely to be associated with aura.^[11] In general, previous studies suggest that those with preexisting headache prior to pregnancy are more likely to experience headache during pregnancy,^[12] and that if headaches do not improve after the first trimester, it may be time to consider more aggressive treatment. As with the use of any treatment during pregnancy, it is important to consider potential maternal and fetal benefits and risks.

Migraine is associated with several maternal complications during pregnancy, including preeclampsia and other hypertensive disorders,^[13–18] dyslipidemia,^[19] and stroke.^[20] As many women will experience new or worsening headache during pregnancy, it is critical to properly assess symptoms, and to rule out the possibility of a secondary headache disorder.^[21] Migraine can also negatively impact women during pregnancy by disrupting food intake and hydration, secondary to migraine-related nausea and vomiting.^[22] In addition, previous studies suggest associations between migraine and poor obstetrical outcomes, including higher occurrence of preterm birth, Cesarean delivery, and low birth weight.^{[13,17,18,23]} Of note, one study from Marozio et al.^[23] studied pregnancy outcomes for both migraine and tension-type headache (in combination and separately), and found that both headache disorder types were significantly associated with preterm delivery. More research is likely needed to study potential differences in pregnancy outcomes by headache disorder type. A population-based Danish study found that infants born to mothers with migraine had a slightly higher risk (risk ratio 1.2–1.3) of hospitalizations (including in the intensive care unit), febrile seizures, and respiratory distress symptoms in their first year of life, compared with infants born to mothers without migraine.^[17] Given these considerations, it is critical to weigh the risks and benefits of prescribing or recommending specific treatments to pregnant women experiencing headaches, as well as to consider when to counsel women about migraine treatment during pregnancy. Treatment of migraine during pregnancy can present significant challenges due to a lack of controlled clinical trials, risks associated with specific medications, and, until very recently, a paucity of standardized treatment guidelines. Previous studies suggest up to 60% of women feel that their clinician does not have sufficient knowledge of migraine treatment during pregnancy, and less than one-third of women feel migraine is optimally treated during their pregnancies.^[24,25] In May 2022, the American College of Obstetricians and Gynecologists (ACOG) released a set of clinical practice guidelines regarding the treatment of headaches in pregnancy and postpartum; this is a critical first step in improving and standardizing migraine care for this special patient population.^[26]

Optimal management of migraine typically involves both pharmacologic and non-pharmacologic treatment approaches. Non-pharmacologic approaches can be particularly beneficial during pregnancy, as many of the suggested lifestyle changes and behaviors can support both healthy pregnancies and migraine prevention. These include healthy diet, eating consistently, practicing good sleep hygiene habits, limiting caffeine use, avoiding alcohol and tobacco use, adequate hydration, and regular moderate exercise.^[27–29] Other non-pharmacologic treatment elements, including cognitive behavioral therapy (CBT), relaxation skills training, and biofeedback, could benefit pregnant women with migraine in the areas of increasing self-efficacy in migraine management, reducing medication use, and improving symptoms of stress, anxiety, and depression.^[30–33] Previous research suggests that utilizing cognitive behavioral approaches for migraine management during pregnancy can reduce migraine frequency, and these benefits can endure for at least 12 months postpartum.^[34] Connecting patients with these treatment approaches prior to pregnancy can help ensure that health habits and CBT skills are learned and implemented prior to conception, for maximum benefit. However, for some patients, non-pharmacologic treatments may not be sufficient, and the risks associated with uncontrolled migraine in pregnancy may call for pharmacologic treatment interventions.

The risks and benefits of pharmacologic treatments must be weighed when considering use during pregnancy. Current knowledge, based on FDA Pregnancy and Lactation Labeling Rule guidelines, recently released ACOG guidelines, and research efforts to date, suggest several treatments that can be considered for first- and second-line treatment of migraine during pregnancy. Several review articles have summarized current data and recommendations.^[35–37] For acute treatment, acetaminophen and antiemetics (i.e., metoclopramide, diphenhydramine) have relatively good safety evidence during pregnancy,^[26,37,38] and large population-based and registry studies also support triptans (specifically sumatriptan) as a potentially safe treatment option.^[37,39–42] ACOG guidelines suggest cautious use of sumatriptan, with a possibility of association with emotionality and negative behavioral outcomes in young children.^[26] Frequent use of opioids is often avoided due to risk of dependency and chance of neonatal withdrawal.^[38] In addition, butalbital-containing compounds are not recommended for migraine treatment during pregnancy, due to risk of overuse and addiction, as well as overall lack of evidence of benefit for migraine treatment in adults.^[26,43] Other acute treatment options are often carefully considered in light of pregnancy trimester and long-term risks. Nonsteroidal anti-inflammatory drugs (NSAIDs), for example, appear to pose different risks based on trimester, with first trimester use potentially linked with increased risk of miscarriage, and third trimester use associated with increased risk of cardiovascular abnormalities (i.e., premature closure of the ductus arteriosus).^[35,44–46] However, further nuances of NSAID use are present, with some evidence suggesting that use of ibuprofen in the first trimester is not associated with adverse outcomes in pregnancy.^[47] In addition, based on a literature review by Dathe and colleagues,^[48] NSAIDs may be safest for use during the second trimester, although long-term use, particularly later in the second trimester, should be closely monitored with risks and benefits considered.^[26] With regard to preventive migraine treatment during pregnancy, ACOG guidelines suggest several medications for first-line treatment, including calcium channel blockers (amlodipine, nifedipine, verapamil) and antihistamines (cyproheptadine, diphenhydramine).^[26,37] In addition, other data suggest beta-blockers (specifically propranolol) appear to have adequate safety data, though maternal and fetal risks/benefits must be weighed.^[26,36] Other medications used for migraine prevention are often avoided due to fetal risks.^[36,49,50] Examples of these include valproic acid, which is contraindicated during pregnancy due to several fetal risks, including neural tube deficits, autism, craniofacial defects, and decreased IQ. In addition, medications such as topiramate increase risk of fetal cleft lip or palate and growth inhibition, and use of candesartan and lisinopril are associated with fetal renal toxicity and possible fetal death with second or third trimester exposure. Peripheral nerve blocks, specifically with lidocaine, appear to show promising results for both acute and preventive treatment of migraine during pregnancy, although safety data in pregnancy are limited.^[26,51] OnabotulinumtoxinA is generally not recommended for use during pregnancy, due to limited data concerning safety during pregnancy.^[26,52] However, some retrospective studies suggest no increased risk with use of onabotulinumtoxinA during pregnancy.^[53,54] Additional population-based and registry studies are needed to continue providing valuable data for providers, including for newer migraine treatments (i.e., calcitonin gene-related peptide monoclonal antibodies).

In addition, it is useful to study the treatment patterns and comfort levels of providers who treat migraine during pregnancy, in order to identify potential knowledge gaps and areas for future study. A recent survey of members of the American Headache Society (AHS), comprised primarily of neurologists, found that most respondents felt comfortable treating migraine in pregnancy, and the majority would start counseling women on migraine treatment in pregnancy as early as pre-pregnancy contemplation.^[55] Nearly 90% reported feeling somewhat or very comfortable recommending acute treatments, and over 70% were somewhat or very comfortable recommending preventive treatments. With regard to specific treatments, the majority of respondents felt very comfortable recommending acetaminophen, dopamine antagonists, nerve blocks with lidocaine, neuromodulation, and non-pharmacologic approaches. The majority of respondents were uncomfortable with butalbital-containing analgesics, opioids, and triptans.^[55] The study highlighted variability in comfort levels with specific acute and preventive treatment approaches, and called for the importance of studying the practices of providers who frequently care for pregnant women with migraine, primarily women's healthcare providers.

The purpose of this study was to survey women's healthcare providers regarding practice patterns and comfort level with use of specific acute and preventive treatments in pregnant women experiencing migraine. Knowledge gained from this study will be an important step toward understanding potential future barriers to implementation of interdisciplinary, standardized guidelines for treatment of migraine during pregnancy, including differences in provider comfort levels and treatment practices.