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Efficacy and safety

Introduction: Hyperemesis Gravidarum (HG) which is a severe and serious condition of pregnancy-related nausea and vomiting and occurs in about 0,5-2% of pregnant women compared to less severe and common nausea and vomiting of pregnancy (NVP) which occurs in about 75% of all pregnant women. NVP and HG treatment regimens coincides with the embryonic developmental phases most sensitive to any possible risk for malformations. First-line treatments such as lifestyle changes, diet changes, ginger, vitamin supplementations, acupressure and acupuncture, should be considered before pharmacological interventions. Studies suggest that promethazine, metoclopramide and ondansetron can all be used for symptomatic relief. Out of these drugs ondansetron is the only off-label prescription substance. There is little good-quality evidence to support any available interventions to be superior to another. The research questions of this study are therefore: Are promethazine, metoclopramide and ondansetron safe and effective treatment options for NVP and HG? Is one therapy regime superior to another? Could NVP/HG be considered indication for ondansetron instead of an off-label option? Method: The study is a literature-based study. Words used and combined to search material were: hyperemesis, gravidarum, infant, nausea, vomiting, pregnancy, treatment, safety, effect, optimal treatment, risk, adverse effect, malformation, antiemetic, ondansetron, promethazine, metoclopramide, compare, randomized. Results: Three studies regarding efficacy were included; ondansetron and metoclopramide showed similar effects although ondansetron showed a slightly better adverse effect-profile. Metoclopramide and promethazine showed similar therapeutic effects but adverse effects were better with metoclopramide. When comparing ondansetron to first-line standard treatment with vitamin supplementation and doxylamine ondansetron was superior. Four studies regarding possible malformations after ondansetron exposure were included and no associations between any increased risks for spontaneous abortions, still birth, unhealthy babies according to size and weight nor any higher risks for birth defects or malformations in the infant were seen. Possibly a higher risk of cardiac septum defects could exist. To conclude the results there is no support for teratogenic risks for ondansetron use for HG and the women treated with ondansetron were actually more likely to report a live birth. Discussion: The fetal development is at its most sensitive period during the same weeks as the NVP/HG peaks, anyhow ondansetron treatment is not associated with any significant increase in malformations above baseline. The reasons for NVP/HG are also discussed and theories of an overall healthy pregnancy due to higher hormonal levels and a well-functioning placenta could be associated with NVP/HG symptoms. Nonpharmacological options and pyridoxine/doxylamine alongside to metoclopramide and promethazine regimes have been used more frequently and for longer time than ondansetron and should therefore be considered first, even though all studies failed to show any statistically increased risks with any pharmacological medication and some studies suggest that ondansetron could be superior to other substances due to better profile regarding vomiting frequency and adverse effects. Conclusion: The safety and effect of promethazine, metoclopramide and ondansetron are validated for treating HG. Non-pharmacological interventions shall remain the first-line treatment. One regime cannot be said to be superior to another. HG after 10th week of pregnancy could possibly be considered an indication for ondansetron while NVP should remain off-label and an option only after other methods have failed. More and larger studies should be undertaken and larger randomized controlled trials are needed to make final conclusions.