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Management of Primary Headaches in Pregnancy

Systematic Review

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Main Points

  • Prevention of primary headache in women who are pregnant (or attempting to become pregnant), postpartum, or breastfeeding with a history of primary headache
    • Pharmacologic and nonpharmacologic interventions
      • There is no evidence regarding the effectiveness of any pharmacologic or nonpharmacologic intervention in women who are pregnant (or attempting to become pregnant), postpartum, or breastfeeding.
      • A single primary study provided insufficient (direct) evidence to make conclusions about the harms of topiramate when used for preventing primary headache during pregnancy, but use during pregnancy outside the primary headache context (indirect evidence) suggests increased risk of fetal/child adverse effects. Indirect evidence also suggests that other antiepileptics, such as carbamazepine, gabapentin, and valproate may have similar adverse effect profiles, but lamotrigine may have a low risk of adverse effects.
      • Venlafaxine, tricyclic antidepressants (any), benzodiazepines (any), beta blockers (any), prednisolone, and oral magnesium use during pregnancy may have increased risk of fetal/child adverse effects, but calcium channel blockers (any, but nifedipine in particular) and antihistamines (any) may have a low risk of adverse effects (indirect evidence).
  • Treatment of patients with acute attacks of primary headache in women who are pregnant (or attempting to become pregnant), postpartum, or breastfeeding
    • Pharmacologic interventions
      • Use of triptans for migraine during pregnancy may not be more harmful than their use before pregnancy (both direct and systematic review evidence). Compared with nonuse (either during or before pregnancy), triptan use may not be associated with spontaneous abortions or congenital anomalies, but may be associated with worse child emotionality and activity outcomes at 3 years of age.
      • A single primary study found that compared with oral codeine, combination metoclopramide and diphenhydramine may be more effective to reduce migraine or tension headache severity during pregnancy, and may not be associated with greater serious or nonserious maternal harms; fetal/child harms were not reported. Indirect evidence found that antihistamines (any) during pregnancy (used for indications other than primary headache) may have a low risk of adverse effects.
      • Systematic reviews of harms (regardless of indication) report that acetaminophen, prednisolone, indomethacin, ondansetron, antipsychotics (any), and intravenous magnesium use during pregnancy may be associated with fetal/child adverse effects, but low-dose aspirin use may not be associated with increased risk of adverse effects.
    • Nonpharmacologic interventions
      • There is insufficient direct evidence to make conclusions about the benefits or harms of acupuncture, thermal biofeedback, relaxation therapy, physical therapy, peripheral nerve blocks, and transcranial magnetic stimulation when used for treatment of primary headache during pregnancy.
      • No indirect evidence regarding harms of nonpharmacologic interventions in pregnancy was identified.

Structured Abstract

Objectives. This systematic review (SR) evaluates the literature on pharmacologic and nonpharmacologic interventions to prevent or treat attacks of primary headaches (migraine, tension headache, cluster headache, and other trigeminal autonomic cephalgias) in women who are pregnant (or attempting to become pregnant), postpartum, or breastfeeding.

Data sources. We searched Medline®, Embase®, Cochrane CENTRAL, CINAHL®, and ClinicalTrials.gov to identify primary studies (comparative studies and single-group studies) in women who are pregnant (or attempting to become pregnant), postpartum, or breastfeeding with primary headache (direct evidence). We searched Medline, the Cochrane Database of Systematic Reviews, and Epistemonikos for existing SRs of harms of interventions in pregnant women regardless of indication (indirect evidence).

Review methods. We extracted study data into the Systematic Review Data Repository. We assessed the risk of bias and evaluated the strength of evidence (SoE) using standard methods. The PROSPERO protocol registration number is CRD42020158310.

Results. Our searches for direct and indirect evidence yielded 8,549 citations and 2,788 citations, respectively. Sixteen primary studies comprising 14,185 patients in total and 26 SRs met criteria. Risk of bias was high for most primary studies. We found no evidence addressing effectiveness of any intervention for prevention of primary headaches. We found one single-group study (of topiramate) and 11 SRs reporting potential harms of various interventions used for primary headache prevention during pregnancy. Antiepileptics (except lamotrigine), venlafaxine, tricyclic antidepressants, benzodiazepines, beta blockers, prednisolone, and oral magnesium may be associated with increased risk of fetal/child adverse effects, but calcium channel blockers and antihistamines may have low risk of adverse effects (indirect evidence; low to moderate SoE). For treatment of acute attacks of primary headache, we found three randomized controlled trials (RCTs), eight nonrandomized comparative studies (NRCSs), and four single-group studies. Combination metoclopramide and diphenhydramine may be more effective than codeine in reducing severity of migraine or tension headache; adverse effect profiles were similar (1 RCT; low SoE). Triptans used for migraine during pregnancy were not associated with spontaneous abortions or congenital anomalies (8 NRCSs; low SoE). Acetaminophen, prednisolone, indomethacin, ondansetron, antipsychotics, and intravenous magnesium may be associated with increased risk of fetal/child adverse effects, but low-dose aspirin (either during pregnancy or postpartum) may not be associated with increased risk (indirect evidence; low to moderate SoE). There is insufficient evidence to make conclusions about the benefits or harms of nonpharmacologic treatments used during pregnancy, including acupuncture (1 RCT); biofeedback, relaxation therapy, and physical therapy (1 RCT and 2 single-group studies); nerve blocks (1 single-group study); and transcranial magnetic stimulation (1 single-group study).

Conclusions. Evidence regarding the benefits and harms of all interventions in women who are pregnant (or attempting to become pregnant), postpartum, or breastfeeding is insufficient, or at best of low strength of evidence. Future research is needed to identify the most effective and safe interventions for preventing or treating primary headaches in these populations of women.

Citation

Saldanha IJ, Roth JL, Chen KK, Zullo AR, Adam GP, Konnyu KJ, Cao W, Bhuma MR, Kimmel HJ, Mehta S, Riester MR, Sorial MN, Balk EM. Management of Primary Headaches in Pregnancy. Comparative Effectiveness Review No. 234. (Prepared by the Brown Evidence-based Practice Center under Contract No. 290-2015-00002-I.) AHRQ Publication No. 20(21)-EHC026. Rockville, MD: Agency for Healthcare Research and Quality; November 2020. DOI: 10.23970/AHRQEPCCER234. Posted final reports are located on the Effective Health Care Program search page.