The efficacy of a drug commonly prescribed against morning sickness in US and Canada is not backed by sufficient scientific evidence, a 40-year-old study has shown. Unpublished until now, the findings had previously been referred to to approve the use of the medicine, a combination of the two molecules pyridoxine (or vitamin B6) and doxylamine.
Morning sickness, characterised by nausea and vomiting, is a very common condition for a large number of women, especially in the first four months of pregnancy. Up to 80% of women experience nausea in the first twelve weeks. Although it can be very unpleasant, it usually does not put the baby's life at risk.
However, in very serious cases, some women may need treatment to go on with their daily lives. In the US and in Canada, millions have been prescribed pyridoxine-doxylamine, marketed as Diclegis in the US (previously Bendectin) and Diclectin in Canada.
An unpublished trial
In the 1970s, a clinical trial conducted by the now defunct Merrell-National Laboratories assessed the safety and efficacy of the combination of pyridoxine-doxylamine as a drug to alleviate morning sickness in the first trimester of pregnancy.
The results were never published, but the Health Canada and the US Food and Drug Administration still mentioned the findings to support its decision to allow the medicine. The United States FDA's initial approval of a drug combining doxylamine and pyridoxine also referred to this unpublished trial.
Now, scientists have published this four-decades old research in the journal PLOS ONE to show that it alone is not sufficient to say that pyridoxine-doxylamine is an effective treatment for morning sickness.
Known as the '8-way Bendectin' trial, the research focused on 2308 patients spread out across 14 clinics across the US and in their first 12 weeks of pregnancy, who complained of nausea or vomiting. The participants were randomly arranged into eight groups, receiving either a placebo or a different combination of pyridoxine-doxylamine.
The study lasted seven days and concluded that the molecules had a positive effect on women's health, reducing the frequency of vomiting and the time spent being nauseous. "The proportion of participants who were "evaluated moderate or excellent" was greater in each of the seven active treatment groups when compared with placebo", the authors wrote at the time.
However, as the paper published in PLOS ONE points out, limitations to the study's design and setting weaken these conclusions. They include the fact that final findings were not available and that a high number of participants did not complete the trial, even though it lasted only one week. Data was unavailable for 37% of participants taking the placebo and the method by which scientists scored symptoms and analysed results was not clear.
This makes it is difficult to assess whether Diclegis and Diclectin really does help women in their early pregnancy.
And in the UK
Unlike the US and Canada, the pyridoxine-doxylamine drug combination is not licensed in the UK. Following guidelines written by the Royal college of obstetricians and gynaecologists (RCOG), doctors take a step-up approach, and prescribe antiemetics. Health professionals consider that there is not enough evidence regarding pyridoxine (or vitamin B6) and doxylamine.
"When we came up with the guidelines for treating vomiting and nausea in pregnancy, what we found was that the evidence out there is not great. This is partly because of the difficulty to organise drug trials during pregnancy and the ethical aspects that must be considered", Dr Manjeet Shehmar, Consultant Obstetrician and Gynaecologist and lead author of the RCOG guidelines, told IBTimes UK.
"We actually thought about including pyridoxine in our guidelines, but a Cochrane review had concluded there was a lack of consistent evidence for it and that it showed no improvements compared to a placebo".
However, she emphasises that it is important for women who have nausea and vomiting during pregnancy to receive appropriate care and medical therapy. "Medicine that are licensed and that have historically been safely given to millions of women may be prescribed and may work for specific patients, even if there is no strong scientific evidence that they are effective", Shehmar concluded.