Nausea and Vomiting in Pregnancy
Vitamin-Based Therapy and Doxylamine
Vitamin B6 is a good initial therapy for women whose nausea and vomiting cannot be managed with dietary change. It has been more widely tested for safety and efficacy than has any other vitamin-based therapy for the problem, and it is inexpensive and widely available.
In a study from our group conducted many years ago, pregnant patients with nausea and vomiting were randomized to 3 days of vitamin B6 or a placebo at a dosage of 25 mg three times a day. Half of the patients stopped vomiting, and most patients with severe nausea reported a diminution to mild or moderate nausea. Several years later, another group of investigators used 10 mg of vitamin B6 three times a day in a larger, randomized, placebo-controlled study. After 5 days of therapy, they also documented a significant decrease in nausea.
A once-a-day, extended-release formulation of vitamin B6 (PremesisRx) is a good first-line option. It delivers 75 mg of vitamin B6 over 24 hours—which is easier than taking 25 mg three times a day—and contains some vitamin B12, calcium carbonate, and 1 mg of folic acid. (The level of folic acid makes the formulation a prescription therapy.)
If vitamin B6 alone is not successful, the antihistamine doxylamine can be added in a combination similar to the formulation that was available in Bendectin from 1956 to 1983. It is estimated that Bendectin was used by more than 30 million women during this time period and, at one point, by approximately 40% of pregnant women.
Although no other agent given in pregnancy has more conclusive safety data with regard to the incidence of birth defects (more than 6,000 patients exposed to the combination have been compared with more than 6,000 controls), Bendectin was removed from the U.S. market in 1983 by the manufacturer because of lawsuits that alleged a teratogenic effect.
The combination has been continually available in Canada as Diclectin (a sustained-release formulation), and interestingly, there are significantly fewer hospitalizations for nausea and vomiting in pregnancy in Canada than in the United States.
A version of the combination can be created by combining vitamin B6 with the over-the-counter sleep aid Unisom SleepTabs, which contains 25 mg of doxylamine per tablet. The dose of doxylamine in Bendectin was 10 mg, and two tablets were recommended at night, so one full tablet of Unisom can be taken at night, along with a half tablet in the morning and a half-tablet in the afternoon if some nausea persists and, of course, 25 mg of vitamin B6 at each of these times of the day.
The combination of vitamin B6 and doxylamine can bring fast and dramatic relief for many patients, leading to significant improvements in the quality of their lives. There is always concern for obstetricians that a mother will claim that a child's birth defect was caused by a drug prescribed during the first trimester, but this is unlikely to happen with the combination of vitamin B6 and doxylamine because legal precedents already hold that the drug does not cause birth defects.
Interestingly, some studies have suggested that women who have taken multivitamins containing vitamin B6 before pregnancy have less nausea and vomiting.
Nonpharmacologic Approaches
Ginger ale has been a traditional remedy for nausea in various populations, and among pregnant women with nausea and vomiting, ginger is the alternative therapy with the strongest evidence base. The data on ginger have accumulated to the point at which concerns about its possible adverse effects have largely dissipated, which makes it worthy of consideration as a second-line agent.
Two small, randomized, double-blind trials used 250-mg ground ginger capsules or placebo four times a day, one in 70 outpatients with nausea and vomiting and one in women who were hospitalized with hyperemesis gravidarum. Investigators of both trials reported significantly reduced nausea and reductions in vomiting among the women in the ginger groups (Obstet. Gynecol. 2001;97:577–82; Eur. J. Obstet. Gynecol. Reprod. Biol. 1990;38:19–24).
Among more recent randomized trials was one of approximately 300 women that compared ginger with vitamin B6. Women who received identical-looking capsules three times a day of 25 mg vitamin B6 or 350 mg ginger had similar levels of improvement in nausea and vomiting at 1 week, 2 weeks, and 3 weeks.
There were no differences in fetal outcome or congenital anomalies; the only difference was that the women taking ginger reported more heartburn and belching (Obstet. Gynecol. 2004;103:639–45).
In a literature review, a group of Italian investigators identified six double-blind, randomized, controlled trials with a total of 675 participants that met criteria for methodological quality for the evaluation of efficacy. Of these six trials, four demonstrated the superiority of ginger over placebo, and two demonstrated the equivalence of ginger with vitamin B6.
