Evidence-Based Answer:
Antihistamines, thiethylperazine (a phenothiazine), pyridoxine (vitamin B6), and ginger are all effective for the relief of nausea. (SOR A, based on a meta-analysis.) The effect of these agents on vomiting is less clear. The combination of pyridoxine and metoclopramide is more effective than prochlorperazine or promethazine given as single agents. (SOR B, based on 1 open-label study.)
In early pregnancy, 70% to 85% of pregnant women will experience nausea and 50% will have vomiting. In addition to physical and mental effects, 35% of women lose time at work and 26% lose housework time secondary to nausea and vomiting.1
A 2003 Cochrane meta-analysis1 identified 28 randomized controlled trials (RCTs) evaluating the effectiveness of various treatments for nausea and vomiting in pregnancy (21 addressing mild nausea and vomiting and 7 addressing hyperemesis gravidarum).
The studies included patients up to 20 weeks of gestational age. Twelve trials with 1,557 participants studied antiemetic drugs, all of which were antihistamines (dimenhydrinate, meclizine, hydroxyzine, doxylamine) or the phenothiazine thiethylperazine. The meta-analysis demonstrated that these medications reduced nausea compared with placebo (odds ratio {OR} 0.16; 95% confidence interval {CI}, 0.08-0.33). However, these medications also increased sleepiness compared with placebo (OR 2.24; 95% CI, 1.05-4.75). The 2 studies of pyridoxine in the Cochrane review involving 395 patients used a visual analogue scale of nausea severity (on a scale of 1-10, with 10 being the worst). There was no evidence that pyridoxine had an effect on vomiting (OR 0.64; 95% CI, 0.18-2.26); however, the evaluation of the nausea symptom scores suggested an effect in reducing the severity of nausea (weighted mean difference {WMD} -0.99; 95% CI, -1.47 to -0.51). The trials used different doses, and 1 trial with 59 patients using a higher dose (75 mg daily) did show an effect on vomiting (OR 0.3; 95% CI, 0.1- 0.9).
This finding suggests a dose-response effect, but the data were insufficient to make this conclusion with confidence. In the Cochrane meta-analysis, ginger was evaluated in 1 placebo-controlled trial of 67 women and found to be beneficial for nausea (OR 0.06; 95% CI, 0.02-0.21) and vomiting (OR 0.31; 95% CI, 0.12-0.85), with no adverse effects.1 A subsequent RCT2 of 291 patients compared ginger 1 g with pyridoxine 75 mg. This study used a 5-item Likert scale, with scores on each item ranging from 0 to 12 (larger scores indicating more symptoms). Both ginger and pyridoxine were associated with an equivalent decrease in nausea (change in score -3.6 for ginger and -3.9 for pyridoxine) and vomiting (-0.9 for ginger and -1.4 for pyridoxine). The Cochrane meta-analysis included 6 trials of 1,309 women receiving acupuncture and P6 acupressure. These procedures were more effective for reducing morning sickness than no treatment (OR 0.25; 95% CI, 0.14-0.43) and sham or dummy acupuncture and acupressure (OR 0.35; 95% CI, 0.12-1.06). However, 2 studies that were not in a form that could be used in a meta-analysis found no benefit. A randomized, open-label comparison trial3 of 174 women demonstrated an advantage in the reduction of nausea and vomiting with the combination of pyridoxine 50 mg intramuscularly daily and metoclopramide 10 mg every 6 hours as needed over prochlorperazine 25 mg rectally every 12 hours or 10 mg orally every 6 hours as needed (relative risk {RR}=0.59; 95% CI, 0.39-0.88) and promethazine 25 mg orally every 6 hours as needed (RR=0.62; 95% CI, 0.42-0.91).
HelpDesk Answer From EBP, Jeremy Kirchoff, MD Corey Lyon, DO Research Family Medicine Residency Program, Kansas City, MO1. Jewell D, Young G.
Interventions for nausea and vomiting in early pregnancy. Cochrane Database Syst Rev. 2003; (4): CD000145. [LOE 1a]
2. Smith C, Crowther C, Willson K, Hotham N, McMillian. A randomized controlled trial of ginger to treat nausea and vomiting in pregnancy. Obstet Gynecol. 2004; 103:639-645. [LOE 1b]
3. Bsat FA, Hoffman DE, Seubert DE. Comparison of three outpatient regimens in the management of nausea and vomiting in pregnancy. J Perinatol. 2003; 23:531-535. [LOE 2b]
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