Abstract and Introduction
Background. Migraine is a common disorder among women of childbearing age. Triptan medications are effective and commonly used to treat migraines in pregnancy. However, the reproductive safety of this group of drugs has not yet been confirmed. The aim of this study was to determine the reproductive safety of triptan medications by performing a literature review and a meta-analysis.
Methods. Available publications regarding pregnancy outcomes following prenatal exposure to triptans from 1991 to 2013 were identified and reviewed according to the inclusion criteria. A random-effects meta-analysis model was implemented to combine the available pregnancy outcome data for the exposed and comparison groups.
Results. One case–control study and 5 cohort studies met the inclusion criteria. The included studies provided information on duration of gestation, major congenital malformations, and spontaneous abortions of infants following prenatal triptan exposure. The 6 studies included 4208 infants of women who used sumatriptan or other triptan medications, and 1,466,994 children of women who did not use triptans during pregnancy. No significant increases in rates for major congenital malformations (MCMs), prematurity, or spontaneous abortions were found when comparing the triptan-exposed group to the migraine – no triptans control group (odds ratio [OR] = 0.84 [0.61–1.16]; OR = 0.90 [0.35–2.30]; OR = 1.27 [0.58–2.79], respectively). There were no increased rate of MCMs (OR = 1.18 [0.97–1.44]) or prematurity (OR = 1.16 (0.67–1.99) when the triptan-exposed group was compared with the healthy controls; however, there was a significant increase in the rates of spontaneous abortions (OR = 3.54 [2.24–5.59]). When the migraine no-triptan group was compared with healthy controls, a significant increase in the rates of MCMs was found (OR = 1.41 [1.11–1.80]).
Conclusion. The use of triptans during pregnancy does not appear to increase the rates for MCMs or prematurity. The increased rates of spontaneous abortions in the triptan-exposed group and the increased rates of MCM in the migraine no-triptan group require further research.
This epidemiologic profile corresponds to women of childbearing age, and the lack of knowledge on reproductive safety of antimigraine medications may represent a significant health concern. Due to the high rate of unplanned and late-diagnosed pregnancies, prenatal exposure to this group of drugs is often unavoidable.
Although about 25% of migraines may be attenuated during pregnancy, the pregnancy hormonal alterations may exacerbate more severe migraine attacks; these migraines may then require pharmacotherapy during pregnancy, including the first trimester: a critical window for embryogenesis.[4–8] Triptans, serotonin 5-hydroxytryptamine agonists, have a well-established efficacy in treating migraine pain. Considering that triptans readily cross the placenta and may have the potential to interfere with fetal development, thus creating a conflict between maternal disease control and fetal teratogenicity, their reproductive safety is essential to study. Furthermore, it is important to separate the effects of triptans from the effects of maternal migraine on fetal and pregnancy outcomes.
Effects of maternal migraine itself on pregnancy outcomes are poorly studied and inconclusive. Some studies have found some association with migraines and increased rates of MCMs; however, others did not find any differences in rates of MCMs, pregnancy duration, and neonatal birth weight when compared with controls.
Sumatriptan was the first triptan proven effective in patients with limited or no response to non-narcotic analgesics.[12,13] A literature review in 1998 warned physicians against the use of triptans during pregnancy; however, a more recent review of available data found no evidence of sumatriptan teratogenicity. The evidence surrounding prenatal safety profiles of triptans is inconclusive because of methodological limitations and limited power of existing studies.[15–17] Emphasizing the absence of adequate or well-controlled studies in pregnant women, sumatriptan received a Food and Drug Administration (FDA)-approved labeling of Pregnancy Category C (animal reproduction studies have shown an adverse effect on the fetus and there are no adequate and well-controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks).
The objective of the present meta-analysis is to study pregnancy outcomes of women prenatally exposed to triptans, aiming to compare these outcomes to comparison groups in order to define the reproductive safety of triptans.
Headache. 2015;55(4):490-501. © 2015 Blackwell Publishing