Abstract and Introduction
Background: Primary headaches (migraine, tension headache, cluster headache, and other trigeminal autonomic cephalgias) are common in pregnancy and postpartum. It is unclear how to best and most safely manage them.
Objective: We conducted a systematic review (SR) of interventions to prevent or treat primary headaches in women who are pregnant, attempting to become pregnant, postpartum, or breastfeeding.
Methods: We searched Medline, Embase, Cochrane CENTRAL, CINAHL, ClinicalTrials.gov, Cochrane Database of SRs, and Epistemonikos for primary studies of pregnant women with primary headache and existing SRs of harms in pregnant women regardless of indication. No date or language restrictions were applied. We assessed strength of evidence (SoE) using standard methods.
Results: We screened 8549 citations for studies and 2788 citations for SRs. Sixteen studies (mostly high risk of bias) comprising 14,185 patients (total) and 26 SRs met the criteria. For prevention, we found no evidence addressing effectiveness. Antiepileptics, venlafaxine, tricyclic antidepressants, benzodiazepines, β-blockers, prednisolone, and oral magnesium may be associated with fetal/child adverse effects, but calcium channel blockers and antihistamines may not be (1 single-group study and 11 SRs; low-to-moderate SoE). For treatment, combination metoclopramide and diphenhydramine may be more effective than codeine for migraine or tension headache (1 randomized controlled trial; low SoE). Triptans may not be associated with fetal/child adverse effects (8 nonrandomized comparative studies; low SoE). Acetaminophen, prednisolone, indomethacin, ondansetron, antipsychotics, and intravenous magnesium may be associated with fetal/child adverse effects, but low-dose aspirin may not be (indirect evidence; low-to-moderate SoE). We found insufficient evidence regarding non-pharmacologic treatments.
Conclusions: For prevention of primary headache, calcium channel blockers and antihistamines may not be associated with fetal/child adverse effects. For treatment, combination metoclopramide and diphenhydramine may be more effective than codeine. Triptans and low-dose aspirin may not be associated with fetal/child adverse effects. Future research should identify effective and safe interventions in pregnancy and postpartum.
Primary headaches, comprising migraine, tension headache, cluster headache, and other trigeminal autonomic cephalgias (TACs), are common during pregnancy, affecting 10%–17% of pregnancies. A recent survey of women with migraine across the United States found that approximately one in five women avoided pregnancy because of migraine; chief concerns noted were that the migraine could worsen during pregnancy (73% of women) or negatively affect their child's development (76%). Although tension headaches are the most common primary headache during pregnancy, migraine is by far the most common primary headache to present to clinical practice, accounting for about 90% of primary headache-related visits to providers during pregnancy. The stresses of pregnancy and imminent infant care may exacerbate the frequency and severity of primary headaches.
Primary headache and its treatment can have significant consequences for the mother, the fetus or child, and mother–child bonding. Treatment decisions must consider both potential benefits and harms, which poses major decisional dilemmas. For example, valproate, an antiepileptic commonly used for preventing migraine outside pregnancy, is contraindicated during pregnancy due to its teratogenicity and adverse neurocognitive outcomes in the child. Similarly, nonsteroidal anti-inflammatory drugs (NSAIDs), commonly prescribed for treating migraine outside pregnancy, can potentially lead to spontaneous abortion (early in pregnancy) and fetal developmental malformations, such as premature closure of the ductus arteriosus and oligohydramnios (in the third trimester). Other therapies used outside of pregnancy, such as complementary and alternative therapies and biologic drugs (e.g., monoclonal antibodies), have unclear and/or mixed safety profiles during pregnancy and lactation. Management of primary headaches other than migraine also poses similar decisional dilemmas.
Given the dual challenges of the uncertainty about the comparative effectiveness and harms of various treatment options and the context of heightened sensitivity about the potential impact of drugs on the fetus or infant, it is crucial to identify effective and safe interventions to manage primary headaches in women who are pregnant, attempting to become pregnant, postpartum, or breastfeeding.
Objective and Key Questions
We conducted a systematic review (SR) under the Agency for Healthcare Research and Quality (AHRQ) Evidence-based Practice Center (EPC) Program to support the American College of Obstetricians and Gynecologists in its effort to develop a new clinical practice guideline on management of primary headaches during pregnancy. We addressed two Key Questions: What are the (comparative) benefits and harms of pharmacologic and non-pharmacologic interventions to (a) prevent or (b) treat acute attacks of primary headache in women who are pregnant, attempting to become pregnant, postpartum, or breastfeeding? For each Key Question, we were also interested in whether the (comparative) benefits and harms varied by phase (i.e., preconception, pregnancy trimester, postpartum, and breastfeeding) or by type of primary headache (i.e., migraine, tension headache, cluster headache, and other TACs).
Headache. 2021;61(1):11-43. © 2021 Blackwell Publishing