Methodological Issues In Epidemiologic Studies Of Drug Effects
Michele Kiely in Reproductive and Perinatal Epidemiology, 2019
Having defined the etiologic period, the challenge remains to identify the relevant chemicals within drug preparations that are suspected of having adverse effects. These pharmacologic agents may be present in many different drug preparations, both prescribed and over-the-counter. For example, Bendectin, a formerly marketed drug that had been prescribed specifically for treatment of pregnancy-related nausea, contains an antihistamine, doxylamine, that is a common ingredient in nonprescription cold medications. In fact, one of these products contains more doxylamine per recommended dose than the prescription product. In this example, the investigated drug was more likely to have been doxylamine, not merely Bendectin. Pooling of different drug preparations to identify truly exposed people becomes more problematic when an ingredient is contained in many different products. Nearly 100 prescription products contain the vasoconstrictive decongestant, phenylpropanolamine hydrochloride; this chemical is common in over-the-counter preparations that also include aspirin and antihistamine. The prescription products may include codeine. The multiple chemical consistency of many drug preparations causes impurity in the classification of exposure of any single agent.
Nutritional and Dietary Supplementation during Pregnancy
“Bert” Bertis Britt Little in Drugs and Pregnancy, 2022
Millions of women used Bendectin during the first trimester of pregnancy with no apparent epidemic of birth defects or adverse fetal effects. Therefore, it seems very unlikely that either doxylamine or pyridoxine is a significant human teratogen. It is generally accepted that neither Bendectin nor its components caused birth defects in human infants. Unfortunately, it does appear that Bendectin was a significant “litogen” (i.e., capable of inducing lawsuits) (Brent, 1983,; Holmes, 1983). A recent paper (Berard et al., 2019) resurrected claims of the possible association of Bendectin components with birth defects, but was quickly followed by a Meta-Analysis (Biffi et al., 2020) that showed no association between Bendectin ingredients and birth defects. The human teratology scientific community does not believe that this combination of drugs (Bendectin) is a cause of birth defects.
Hope Amid Uncertainty: 1950 to 2000
John K. Crellin in A Social History of Medicines in the Twentieth Century, 2020
It is certainly difficult to refute charges—accepted by the courts from time to time—that the industry (at least certain companies) deliberately withheld negative information about the side effects of medicines from doctors and the public. An early notorious case was the 1960s' indictment of the Richardson-Merrell pharmaceutical company for falsifying data, lying to the FDA, and withholding information concerning the hazards of MER/29, an anticholesterol medicine that caused cataracts, among other side effects. Litigation by sufferers continued for many years.43 The same company, known later as Merrell Dow Pharmaceuticals, faced other litigation from plaintiffs with serious limb defects allegedly due to their mothers taking Bendectin, a product marketed to relieve morning sickness that was voluntarily withdrawn in 1983 but with uncertainty about its safety continuing to reverberate into the 2000s.44 The 1950s and 1960s also saw the beginnings of a long, drawn-out saga of the dangerous side effects of chloramphenicol—something of a cause célèbre as noted earlier—that also raised questions about manufacturers' truthfulness.45 Among similar noteworthy episodes to punctuate the second half of the century amid a series of withdrawals of products and changes in recommended dosages are the sagas of Entero-Vioform,46 Halcion,47 and Opren;48 these products contributed to public uncertainty, if only through the public airing of clashes of testimony from experts. These differing viewpoints in the medical community have occurred in other, often extraordinary, controversies, as with the question of whether vitamin C can treat cancer, a theory that began in the 1970s.49
A systematic review of the efficacy of alternative medicine in the treatment of nausea and vomiting of pregnancy
Published in Journal of Obstetrics and Gynaecology, 2020
Fahimeh Khorasani, Hossein Aryan, Abousaleh Sobhi, Reihaneh Aryan, Arefeh Abavi-Sani, Masumeh Ghazanfarpour, Masumeh Saeidi, Fatemeh Rajab Dizavandi
The non-pharmacological therapy of NVP during pregnancy is underpinned by a change of nutritional habits, lifestyle and medications, which have received scant attention in the literature (Soltani et al. 2017). The drugs widely used to treat the mild to moderate cases of NVP are pyridoxine, antihistamines, metoclopramide, pyridoxine/doxylamine, promethazine and metoclopramide. In the event of more severe symptoms, ondansetron and corticosteroids can be prescribed. However, there is little on the efficacy of these drugs. Many mothers feel helpless in dealing with this condition, especially out of concern for side effects of these drugs on the unborn foetus (Viljoen et al. 2014).
Interventions for treating nausea and vomiting in pregnancy: a network meta-analysis and trial sequential analysis of randomized clinical trials
Published in Expert Review of Clinical Pharmacology, 2018
Kannan Sridharan, Gowri Sivaramakrishnan
The protocol of this review was registered with PROSPERO with the registration number CRD42017072184. We searched PubMed, Cochrane CENTRAL, and Google Scholar for eligible articles with the following search strategy: (((((morning sickness [tiab] OR nausea [tiab] OR vomiting [tiab] OR hyperemesis [tiab] OR pregnancy [tiab] OR pregnant [tiab] OR Hyperemesis Gravidarum/diet therapy[Mesh] OR Hyperemesis Gravidarum/drug therapy[Mesh])) AND (acupuncture [tiab] OR acupressure [tiab] OR debendox [tiab] OR diclectin [tiab] OR doxinate [tiab] OR dimenhydrinate [tiab] OR peppermint [tiab] OR almond [tiab] OR bendectin [tiab] OR cardamom [tiab] OR diclegis [tiab] OR psychotherapy [tiab] OR lavender [tiab] OR prochlorperazine [tiab] OR dicyclomine [tiab] OR acustimulation [tiab] OR thiethylperazine [tiab] OR mint oil [tiab] OR fluphenazine [tiab] OR chamomile [tiab] OR lemon [tiab] OR hypnosis [tiab] OR trance induction [tiab] OR diazepam [tiab] OR benzodiazepines [tiab] OR phenothiazines [tiab] OR alternative medicine [tiab] ORhydroxyzine [tiab] OR complementary [tiab] OR ginger [tiab] OR garlic [tiab] OR doxylamine [tiab] OR corticosteroids [tiab] OR prednisol* [tiab] OR hydrocort* [tiab] OR ACTH [tiab] OR adrenocorticotrophic hormone [tiab] OR promethazine [tiab] OR anti histamines [tiab] OR antihistamines [tiab] OR anti-histamines [tiab] OR metoclopramide [tiab] OR pyridoxine [tiab] OR vitamin B6 [tiab] OR ondansetron [tiab] OR anti emetic[tiab] OR anti-emetic [tiab] OR antiemetic[tiab] OR dopamine antagonist [tiab] OR serotonergic receptor antagonist [tiab] OR serotonin antagonist [tiab])) AND (randomized [tiab] OR randomised [tiab] OR RCT [tiab] OR clinical trial [tiab]))) NOT review [pt]. No limit was placed with respect to language and studies carried out from 1980 until 2017 were included in the present review. We also hand-searched for appropriate studies from the references listed in the eligible articles.
Related Knowledge Centers
- Doxylamine
- Intelligence Quotient
- Pyridoxine
- Teratology
- Vitamin B6
- Morning Sickness
- Vitamin
- Meta-Analysis
- Dicycloverine
- Pregnancy Category