Migraine Treatment in Pregnancy and Lactation

DOI: https://doi.org/10.1007/s11916-017-0646-4

Abstract-Summary A review of articles published in the last year on the treatment of migraine during pregnancy and lactation found dishearteningly little.

This article will review the risk/safety information related to migraine treatment

in both pregnancy and lactation, citing both new and less recent publications.

There is little if any formal research is being carried out on pharmacotherapy for

migraine that occurs during pregnancy or lactation.

Treatment in Pregnancy Categories B and C—which lay in between—were defined thus as follows: Animal reproduction studies have failed to demonstrate a risk to the fetus, and there are no adequate and well-controlled studies in pregnant women.

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.

Since adequate, well-controlled studies in pregnant women are rarely if ever done, the difference between Categories B and C was simply determined by the outcomes of animal studies.

4.5 Pregnancy

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Two of its three component drugs (butalbital and caffeine), though, are Category

C, and the third (acetaminophen) had inadequate studies in animals.

Migraine Treatment During Pregnancy Associations between NSAID exposure in pregnancy and congenital malformations have been assessed in studies covering more than 20,000 pregnancies [414].

This data included a prospective pregnancy registry that was conducted in the US and Canada [415] as well as the large Norwegian Mother and Child Cohort in which 2.2% of the 69,929 pregnant women in the study used a triptan during pregnancy (mostly sumatriptan).

There was no association between triptan use during pregnancy and congenital malformations compared to controls; adjusted odds ratios were 0.9 (0.7–1.2) for any malformation and 1.0 (0.7–1.3) for major congenital malformation [416].

One case-control study and five-cohort studies met inclusion criteria and pro- vided data on 4208 infants of women who used triptans (mostly sumatriptan), and 1,466,994 children of female migraineurs who did not use triptans during pregnancy.

Preventive Treatments in Pregnancy Subjects then received either five behavioral sleep modification (BSM) instructions or five placebo instructions (that addressed diet and exercise).

By the second visit, the BSM group reported a statistically significant reduction in headache frequency and intensity compared to the placebo group and had a high likelihood of reverting to episodic migraine.

By the third visit, 48.5% of all subjects had reversed over 11 years of chronic

migraine and reverted to episodic.

Among participants who adhered to all five BSM instructions, only one did not revert to episodic (a subject who was sleeping with a pet that she was allergic to; she immediately gave the pet to a relative, then she reverted as well); nonadherence with three or more instructions was associated with no reversion to episodic.

Treatment in Lactation How much drug transfers into breast milk is commonly described quantitatively using the milk to plasma (M/P) concentration ratio, whereby the infant dose (mg/ kg) is expressed as a percentage of the maternal dose (mg/kg) [417].

The authors provide recommendations for breastfeeding, basing their judgment on data such as milk and maternal plasma levels, infant drug levels after exposure, and reported adverse events.

When a drug is compatible with breastfeeding, the next concern is the concentra-

tion of that drug that will be present in breast milk.

Virtually all drugs taken by the mother will be present to some extent in breast milk, but the relative infant dose (RID) can be determined and expressed as a per- centage of the maternal dose.

As rizatriptan is concentrated in rat breast milk, with RID at least five-times higher than maternal plasma concentrations [418], it would not be a good choice for use during lactation until further information is available.

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Conclusion Migraine is a common problem in women who are pregnant or breastfeeding, yet there is inadequate clear information for these patients on appropriate and safe treatment.

They could furthermore research and promulgate the best treatments of medical conditions that occur during pregnancy and lactation. (2) Because of the concern related to litigation when birth defects occur (affecting 3–5% of all pregnancies), an official list of drugs that are considered “legally safe” in pregnancy should be devel- oped and maintained, in keeping with the best medical information at the time.

A similar “legally safe” list should be developed for treatment during lactation to avoid any concern that providers might otherwise experience related to potential lawsuits for conditions that might develop years later.

Let us remember the Norwegian women cited in the opening reference [419]: they clearly expressed frustration with the conflicting information they received related to treatment of their migraines during pregnancy and lactation.

[Section 6] Most headache centers report that roughly 85% of their migraine patients are women—and at least 70% of female migraineurs report menstrual association of their attacks, as well as changes in their headaches related to hormonal contracep- tion, pregnancy, and menopause.

Almost three quarters of them confirmed that they had looked for safety informa-

tion related to their acute and preventive migraine agents during pregnancy.

Although observational studies have shown that migraine tends to improve dur- ing pregnancy [420], some women experience an increase in frequency or intensity [421], particularly towards the end of the first trimester when human chorionic gonadotropin levels are falling.

When improvement is not seen after this point, migraine is likely to continue

throughout the pregnancy and extend into the postpartum period [422].

In women who bottle-feed, the frequency of migraine attacks that they experi- enced prior to the pregnancy tends to recur very quickly; women who breastfeed tend to maintain the protective effect of anovulatory cycles for an extended period, usually until their menses resume [422].

Acknowledgement A machine generated summary based on the work of Calhoun, Anne H. 2017  in Current Pain and Headache Reports.

Patterns and predictors of analgesic use in pregnancy: a longitudinal drug utilization study with special focus on women with migraine