I had the privilege of caring for pregnant mothers for over 20 years (delivering over 1500 babies). During that tenure, I would tell moms, “I do NOT want you to experience ANY morning sickness during your pregnancy.” And, following the advice below, the vast majority did not! (Last Updated July 24, 2024)

If you want to “cut to the chase,” Up-To-Date (a publication I love and use often) has a complimentary flowsheet (algorithm) available here and a complimentary article here. Although both are published (in an expensive subscription) for clinicians, you may find the information useful.

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MY ORIGINAL POST (which has been updated — see below)

Only about one-third of “morning sickness” occurs in the morning. About 1/3 occurs in the afternoon or evening. And, about 1/3 of women have it all day! No matter when nausea and vomiting during pregnancy occurs, using my recommendations, I found I seldom had to use any prescription remedies.

First of all, before turning to medications (prescription or over-the-counter), you should have tried more conservative approaches such as dietary changes, meals and snacks, fluids, and avoiding triggers (you can read more about these here).

But, if these were not effective, what do I recommend?

Before I tell you, let me recount for you the very sad story of a medication called “Bendectin.” Bendectin  was a mixture of pyridoxine (Vitamin B6) and doxylamine (an antihistamine) that was prescribed to treat nausea and vomiting associated with morning sickness. It was nearly 100% effective. So why is it taken off the market in the U.S.?

The manufacturer, Merrell Dow Pharmaceuticals, spent more than $100 million defending the subsequent personal injury lawsuits, winning courtroom victories in virtually all of their cases. Nevertheless, to reduce litigation expenses, the company voluntarily removed the drug from the U.S. market in 1983. Not only did an FDA panel conclude there was no association between Bendectin and birth defects, but over 30 epidemiologic studies have concluded that Bendectin was safe for use in pregnancy. Also, the World Health Organization and the March of Dimes have exonerated the drug. The Centers for Disease Control and Prevention hasn’t found any reduction in birth defects nationally since Bendectin was pulled from the market. The most famous case involving the drug is Daubert v. Merrell Dow Pharmaceuticals (1993). These suits were led by flamboyant plaintiff attorney Melvin Belli. The star witness for the case against Bendectin, William McBride, was later found to have falsified research on the teratogenic effects of the drug and was disbarred in Australia. The drug continues to be used around the world (not only in Canada and the UK but also across Europe) and no subsequent epidemiological studies have found any teratogenic effect. Bendectin consisted of 10 mg of pyridoxine (vitamin B6) and 10 mg of the antihistamine, doxylamine, combined in a single tablet. It could be taken up to four times per day.

UPDATE: “Bendectin” is available as Debendox in the United Kingdom and Diclectin in Canada. In the U.S. it is now available as prescription Diclegis (each tablet contains doxylamine 10 mg and pyridoxine 10 mg. As a generic, it can cost over $1 per tablet) and Bonjesta (20 mg of doxylamine succinate and 20 mg of pyridoxine. Not available as a generic. The brand name product costs over $10 per tablet).

However, you can create a “do-it-yourself” Bendectin by purchasing pyridoxine scored 25 mg tablets (for less than 15 cents a tablet) and pop them in half — although if not scored, you may need to purchase a pill splitter.

UPDATE 2024: Up-To-Date advises, “The combination extended-release tablets may be costly. In the United States, doxylamine is available in some over-the-counter sleeping pills (eg, Unisom Sleep Tabs) and as a prescription antihistamine chewable tablet (eg, Aldex AN): One-half of the 25 mg over-the-counter tablet or two chewable 5 mg tablets can be used off-label as an antiemetic. Pyridoxine (vitamin B-6) 25 mg, also available over-the-counter, can be taken three or four times per day along with 12.5 mg of doxylamine (the 10 mg dose of pyridoxine is not commercially available in the United States). This is a reasonable, less expensive substitute for combination extended-release tablets. The combination of doxylamine-pyridoxine was proven modestly effective for treatment of NVP in a meta-analysis of placebo-controlled randomized trials and appears to be more effective than either therapy alone. Less information is available on doxylamine alone, but available data are reassuring.”

Since doxylamine is sleep-inducing, I had my patients follow this recipe:

1. Start with 10-12.5 mg of pyridoxine (vitamin B6) three times a day for 2 days. If not fully effective,
2. Increase to 12.5 mg of pyridoxine four times a day for 2 days. If not fully effective,
3. Increase to 25 mg of pyridoxine three times a day for 2 days. If not fully effective,
4. Continue 25 mg of pyridoxine 3 times a day, and add 12.5 mg of doxylamine before bedtime each day for 2 days. If not fully effective,
5. Continue 25 mg of pyridoxine 3 times a day, and take 12.5 mg of doxylamine twice a day. If not fully effective,
6. Continue 25 mg of pyridoxine 3 times a day, and take 12.5 mg of doxylamine three times a day. If not fully effective,
7. Continue 25 mg of pyridoxine 3 times a day, and 12.5 mg of doxylamine 3 times a day, while adding Emetrol, one to two tablespoons (15-30 cc) taken once or twice a day as needed. (Emetrol is an over-the-counter mixture of sugar syrups and phosphoric acid [phosphorylated carbohydrate solution]) that acts by soothing the actual wall of the gastrointestinal tract and can be found for about $2 per ounce). If not fully effective,
8. Consult with your doctor.

Once you find your effective dose, continue it for a week or two and then “walk back down the dosing ladder” to find the lowest effective dose of medication to keep your nausea away. After a few weeks, you may be able to discontinue the treatment altogether.

I do not recommend more than 25 mg of pyridoxine three times a day. Why? A total daily dose of pyridoxine of more than 75 mg a day in pregnancy may cause problems with the nerves (neurotoxicity).

But, what if my recipe does not work?

I used to recommend oral ginger capsules. But, reports began to circulate questioning the use of ginger during pregnancy. The Finnish government warned pregnant women not to consume ginger supplements, drinks, or teas. Why? They were concerned that ginger can contain chemicals that are cytotoxic in vitro and MIGHT be harmful to the unborn baby if consumed in large quantities. So far, no obvious problems have been seen in pregnant women taking ginger supplements in doses of about one gram (1000 mg) daily. But, I think it’s better to be safe than sorry.

UPDATE 2024: Up-To-Date advises, “Patients can now try ginger-containing foods (eg, ginger lollipops, ginger tea, foods or drinks containing ginger root or syrup). Powdered ginger is not available as a standard pharmacologic-grade ginger preparation; however, if prescribed, a common dose is 1 to 1.5 g orally divided over 24 hours (eg, 250 mg ginger capsules orally four times a day); doses of 0.5 to 2.5 g orally over 24 hours have been used and appear to be safe. In meta-analyses of randomized trials, ginger improved nausea compared with placebo but did not significantly reduce vomiting.” UTD notes, “Ginger is considered a first-line nonpharmacological treatment option for nausea in pregnancy by the American College of Obstetrics and Gynecology (ACOG).” In addition, NatMed(subscription) considers ginger “Possibly Safe … when used for medicinal purposes in pregnancy.”

So what is your doctor left with if the OTC meds do not work for you? A number of prescription medicines. Fortunately, I have rarely had to use any of these:

1. Metoclopramide (Reglan), even though in the U.S. it only has FDA approval for use as a treatment for patients suffering heartburn and esophagitis due to acid reflux. Nevertheless, it’s often recommended as a treatment for morning sickness if other therapies have failed and appears to be a safe and effective treatment for morning sickness. MOVED UP TO #1 ON THE LIST IN 2014. READ THE UPDATE BELOW.
2. Prochlorperazine (Compazine).
3. Promethazine (Phenergan).
4. Zofran (Ondansetron) is a  very powerful antiemetic. Its exact mechanism of action is unknown. MOVED DOWN FROM #2 to #5 in 2014. In 2015, it was NOT recommended by ACOG, but is now recommended by Up-To-Date. SEE THE UPDATES BELOW.

If you give my recipe a try, leave a note for me and our other readers about what dose worked for you.

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AUGUST 2024 UPDATE:

Up-To-Date, in its article, “Treatment of nausea and vomiting of pregnancy (NVP),” now recommends this sequence for NVP, going to the next step only if the initial step is ineffective:

1. Begin dietary changes and trigger avoidance
2. Ginger and/or pyridoxine
3. Add doxylamine-pyridoxine if on ginger only; switch to doxylamine-pyridoxine if on pyridoxine
4. Discontinue doxylamine-pyridoxine and begin dimenhydrinate or diphenhydramine
5. Add metoclopramide (Reglan), promethazine (Phenergan), or prochlorperazine (Compazine)
6. Add ondansetron
7. Add glucocorticoids

UTD advises, “When initiating a new medication, we typically continue it for a week to determine whether symptoms are improving. If the patient does not have adequate improvement, then adding another class of medication to the existing regimen is necessary, with careful monitoring for side effects while trying different combinations of pharmacotherapies to see what works.”

They have a great flowsheet (algorithm) with more details here. Their detailed article is available here at no charge.

JUNE 2023 UPDATE: A study just published the in Annals of Internal Medicine, titled, “Acupuncture and Doxylamine–Pyridoxine for Nausea and Vomiting in Pregnancy, A Randomized, Controlled, 2 × 2 Factorial Trial, concluded, “Acupuncture and doxylamine-pyridoxine alone and the combination of the two were effective in reducing morning sickness symptoms during pregnancy.” The authors warned, “Compared with placebo, a higher risk for births with children who were small for gestational age was observed with doxylamine–pyridoxine;” nevertheless, they concluded, “Both acupuncture and doxylamine–pyridoxine alone are efficacious for moderate and severe NVP (nausea and vomiting in pregnancy). However, the clinical importance of this effect is uncertain because of its modest magnitude. The combination of acupuncture and doxylamine–pyridoxine may yield a potentially larger benefit than each treatment alone.”

See more details in Primary Care Notebook here. The authors note:

1. The rationale for the delayed-release characteristics of this combination is to allow women to take it before bedtime, when symptoms of NVP tend to be minimal, in order to counteract the increased symptoms more commonly experienced in the morning hours.
2. Doxylamine succinate-pyridoxine hydrochloride delayed release combination is safe and well tolerated by pregnant women when used in the recommended dose of up to 4 tablets daily in treating nausea and vomiting of pregnancy.
3. Extensive data suggest that doxylamine/pyridoxine is safe for pregnant women to use and that it is relatively well tolerated. The results of epidemiological studies designed to detect possible teratogenicity show no association with fetal abnormalities.

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SEPTEMBER 2015 UPDATE: In updating 11-year-old guidelines on treating morning sickness, the American College of Obstetricians and Gynecologists (ACOG) now suggests women pair vitamin B6 and the antihistamine doxylamine to treat persistent, disruptive nausea and vomiting. The medications are sold separately over the counter or combined in prescription form. Meanwhile, further review of a commonly used morning sickness drug, ondansetron (Zofran), has prompted ACOG to pull back on supporting its use since more recent data suggest the drug may be linked to birth defects.

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JANUARY 2014 UPDATE: This, just out from the experts at the Prescriber’s Letter (2014(Jan); 21(1): 5:

Questions will come up about using ondansetron for morning sickness. It was thought to be relatively safe … but now there are concerns. Ondansetron use in the first trimester is linked to a two-fold increase in the risk of congenital heart defects and cleft palate. Plus ondansetron prolongs the QT interval … and electrolyte disturbances due to vomiting can increase the risk of torsades.
When drug therapy is needed for morning sickness, recommend OTC pyridoxine AND doxylamine 12.5 to 25 mg up to TID … or use the Rx combo product, Diclegis. But point out that Diclegis can cost over $500/month. If pyridoxine and doxylamine are not enough, try metoclopramide or a phenothiazine (prochlorperazine, etc). Save ondansetron for when other options aren’t enough. Monitor ECG and electrolytes for women with significant vomiting.

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OCTOBER 2013 UPDATE: I am happy to let my readers know that (1) this is by far the most popular (and, I hope, helpful) blog I’ve written, and (2) the U.S. Food and Drug Administration just approved Diclegis® (doxylamine succinate 10mg, pyridoxine hydrochloride 10mg) delayed-release tablets, the first prescription treatment for nausea and vomiting of pregnancy (NVP) when conservative management fails in more than 30 years. However, it’s not cheap. In our area (Colorado Springs), the least expensive price for 30 tablets is about $155.00. For some women, it can cost over $500/month. But, for those with insurance, it may well be worth considering.

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