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United European Gastroenterology Journal Jul 2023Consensus guidelines recommend the use of multiple antiemetics as prophylaxis in patients at high risk of postoperative nausea and vomiting (PONV), but the evidence... (Randomized Controlled Trial)
Randomized Controlled Trial
Acupuncture combined with ondansetron for prevention of postoperative nausea and vomiting in high-risk patients undergoing laparoscopic gynaecological surgery: A randomised controlled trial.
BACKGROUND
Consensus guidelines recommend the use of multiple antiemetics as prophylaxis in patients at high risk of postoperative nausea and vomiting (PONV), but the evidence regarding combining acupuncture and antiemetics as a multimodal approach was of very low quality.
OBJECTIVE
This study aimed to assess the effect of combinations of acupuncture with ondansetron versus ondansetron alone for PONV prophylaxis in women at a high risk.
METHODS
This parallel, randomised controlled trial was conducted in a tertiary hospital in China. Patients who had three or four PONV risk factors on the Apfel simplified risk score, undergoing elective laparoscopic gynaecological surgery for benign pathology, were recruited. Patients in the combination group received two sessions of acupuncture treatment and 8 mg intravenous ondansetron, whereas those in the ondansetron group received ondansetron alone. The primary outcome was the incidence of PONV within 24 h postoperatively. Secondary outcomes included the incidence of postoperative nausea, postoperative vomiting, adverse events etc. RESULTS: Between January and July 2021, a total of 212 women were recruited, 91 patients in the combination group and 93 patients in the ondansetron group were included in the modified intention-to-treat analysis. In the first 24 h postoperatively, 44.0% of the patients in the combination group and 60.2% of the patients in the ondansetron group experienced nausea, vomiting, or both (difference, -16.3% [95% CI, -30.5 to -2.0]; risk ratio, 0.73 [95% CI, 0.55-0.97]; p = 0.03). However, the results of the secondary outcomes showed that compared to ondansetron alone, acupuncture together with ondansetron was only effective in reducing nausea but did not have a significant impact on vomiting. The incidence of adverse events was similar between the groups.
CONCLUSION
Acupuncture combined with ondansetron as a multimodal prophylaxis approach is more effective than ondansetron alone in preventing postoperative nausea in high-risk patients.
Topics: Humans; Female; Ondansetron; Postoperative Nausea and Vomiting; Antiemetics; Gynecologic Surgical Procedures; Laparoscopy; Acupuncture Therapy
PubMed: 37318120
DOI: 10.1002/ueg2.12421 -
British Journal of Clinical Pharmacology Oct 2022The objective of this study was to describe ondansetron drug utilization patterns during pregnancy to treat nausea and vomiting in pregnancy (NVP). Moreover, we aimed to...
AIMS
The objective of this study was to describe ondansetron drug utilization patterns during pregnancy to treat nausea and vomiting in pregnancy (NVP). Moreover, we aimed to describe the maternal factors associated with NVP and antiemetic use.
METHODS
The data consist of pregnancies with a live birth(s) within an IMRD-UK registered GP practice. Descriptive statistics were used to investigate patterns of ondansetron use in pregnancy and to describe maternal characteristics associated with NVP and antiemetic drug utilization. We differentiate first- from second-line use during pregnancy using antiemetic prescription pathways.
RESULTS
The dataset included 733 633 recorded complete pregnancies from 2005 to 2019. NVP diagnosis and ondansetron prescription prevalence increased from 2.7% and 0.1% in 2005 to 4.8% and 2.5% in 2019 respectively. Over the period 2015-2019, the most common oral daily dosages were 4 mg/d (8.5%), 8 mg/d (37.1%), 12 mg/d (37.5%) and between 16 and 24 mg/d (16.9%). Prescription of ondansetron was initiated during the first trimester of pregnancy in 40% of the cases and was moderately used as a first-line therapy (2.8%), but preferred choice of second-line therapy. Women with mental health disorders, asthma and/or prescribed folic acid were more likely to experience NVP and use antiemetics in pregnancy than their counterparts.
CONCLUSION
This study confirms that ondansetron is increasingly used off-label to treat NVP during pregnancy, also in the first trimester and before other prescription antiemetics have been prescribed. Several maternal comorbidities and folic acid use were more common among women experiencing NVP and using antiemetics, including ondansetron.
Topics: Antiemetics; Female; Folic Acid; General Practice; Humans; Nausea; Ondansetron; Pregnancy; Pregnancy Complications; Prescriptions; United Kingdom; Vomiting
PubMed: 35483963
DOI: 10.1111/bcp.15370 -
Health Technology Assessment... Nov 2021Around one-third of pregnant women suffer from moderate to severe nausea and vomiting, causing physical and emotional distress and reducing their quality of life. There... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Around one-third of pregnant women suffer from moderate to severe nausea and vomiting, causing physical and emotional distress and reducing their quality of life. There is no cure for nausea and vomiting in pregnancy. Management focuses on relieving symptoms and preventing morbidity, and often requires antiemetic therapy. National guidelines make recommendations about first-, second- and third-line antiemetic therapies, although care varies in different hospitals and women report feeling unsupported, dissatisfied and depressed.
OBJECTIVES
To determine whether or not, in addition to intravenous rehydration, ondansetron compared with no ondansetron and metoclopramide compared with no metoclopramide reduced the rate of treatment failure up to 10 days after drug initiation; improved symptom severity at 2, 5 and 10 days after drug initiation; improved quality of life at 10 days after drug initiation; and had an acceptable side effect and safety profile. To estimate the incremental cost per treatment failure avoided and the net monetary benefits from the perspectives of the NHS and women.
DESIGN
This was a multicentre, double-dummy, randomised, double-blinded, dummy-controlled 2 × 2 factorial trial (with an internal pilot phase), with qualitative and health economic evaluations.
PARTICIPANTS
Thirty-three patients (who were < 17 weeks pregnant and who attended hospital with nausea and vomiting after little or no improvement with first-line antiemetic medication) who attended 12 secondary care NHS trusts in England, 22 health-care professionals and 21 women participated in the qualitative evaluation.
INTERVENTIONS
Participants were randomly allocated to one of four treatment groups (1 : 1 : 1: 1 ratio): (1) metoclopramide and dummy ondansetron; (2) ondansetron and dummy metoclopramide; (3) metoclopramide and ondansetron; or (4) double dummy. Trial medication was initially given intravenously and then continued orally once women were able to tolerate oral fluids for a maximum of 10 days of treatment.
MAIN OUTCOME MEASURES
The primary end point was the number of participants who experienced treatment failure, which was defined as the need for further treatment because symptoms had worsened between 12 hours and 10 days post treatment. The main economic outcomes were incremental cost per additional successful treatment and incremental net benefit.
RESULTS
Of the 592 patients screened, 122 were considered eligible and 33 were recruited into the internal pilot (metoclopramide and dummy ondansetron, = 8; ondansetron and dummy metoclopramide, = 8; metoclopramide and ondansetron, = 8; double dummy, = 9). Owing to slow recruitment, the trial did not progress beyond the pilot. Fifteen out of 30 evaluable participants experienced treatment failure. No statistical analyses were performed. The main reason for ineligibility was prior treatment with trial drugs, reflecting an unpredicted change in prescribing practice at several points along the care pathway. The qualitative evaluation identified the requirements of the study protocol, in relation to guidelines on anti-sickness drugs, and the diversity of pathways to care as key hurdles to recruitment while the role of research staff was a key enabler. No important adverse events or side effects were reported.
LIMITATIONS
The pilot trial failed to achieve the recruitment target owing to unforeseen changes in the provision of care.
CONCLUSIONS
The trial was unable to provide evidence to support clinician decisions about the best choice of second-line antiemetic for nausea and vomiting in pregnancy.
TRIAL REGISTRATION
Current Controlled Trials ISRCTN16924692 and EudraCT 2017-001651-31.
FUNDING
This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in ; Vol. 25, No. 63. See the NIHR Journals Library website for further project information.
Topics: Antiemetics; Cost-Benefit Analysis; Female; Humans; Metoclopramide; Nausea; Ondansetron; Pregnancy; Quality of Life; Vomiting
PubMed: 34782054
DOI: 10.3310/hta25630 -
American Family Physician Apr 2015
Review
Topics: Adolescent; Antiemetics; Child; Diarrhea; Gastroenteritis; Humans; Ondansetron; Vomiting
PubMed: 25884755
DOI: No ID Found -
Alimentary Pharmacology & Therapeutics Jun 2023Ondansetron may be beneficial in irritable bowel syndrome with diarrhoea (IBS-D). (Meta-Analysis)
Meta-Analysis
BACKGROUND
Ondansetron may be beneficial in irritable bowel syndrome with diarrhoea (IBS-D).
AIM
To conduct a 12-week parallel group, randomised, double-blind, placebo-controlled trial of ondansetron 4 mg o.d. (titrated up to 8 mg t.d.s.) in 400 IBS-D patients.
PRIMARY ENDPOINT
% responders using the Food and Drug Administration (FDA) composite endpoint. Secondary and mechanistic endpoints included stool consistency (Bristol Stool Form Scale) and whole gut transit time (WGTT). After literature review, results were pooled with other placebo-controlled trials in a meta-analysis to estimate relative risks (RR), 95% confidence intervals (CIs) and number needed to treat (NNT).
RESULTS
Eighty patients were randomised. On intention-to-treat analysis, 15/37 (40.5%; 95% CI 24.7%-56.4%) met the primary endpoint on ondansetron versus 12/43 (27.9%; 95% CI 14.5%-41.3%) on placebo (p = 0.19). Ondansetron improved stool consistency compared with placebo (adjusted mean difference - 0.7; 95% CI -1.0 to-0.3, p < 0.001). Ondansetron increased WGTT between baseline and week 12 (mean (SD) difference 3.8 (9.1) hours, versus placebo -2.2 (10.3) hours, p = 0.01). Meta-analysis of 327 patients from this, and two similar trials, demonstrated ondansetron was superior to placebo for the FDA composite endpoint (RR of symptoms not responding = 0.86; 95% CI 0.75-0.98, NNT = 9) and stool response (RR = 0.65; 95% CI 0.52-0.82, NNT = 5), but not abdominal pain response (RR = 0.95; 95% CI 0.74-1.20).
CONCLUSIONS
Although small numbers meant the primary endpoint was not met in this trial, when pooled with other similar trials meta-analysis suggests ondansetron improves stool consistency and reduces days with loose stool and urgency. Trial registration - http://www.isrctn.com/ISRCTN17508514.
Topics: Humans; Irritable Bowel Syndrome; Ondansetron; Diarrhea; Double-Blind Method; Feces; Treatment Outcome; Randomized Controlled Trials as Topic
PubMed: 36866724
DOI: 10.1111/apt.17426 -
Alcoholism, Clinical and Experimental... Oct 2022In a previous study, ondansetron, a serotonin 5-HT receptor antagonist, reduced drinking intensity (drinks/drinking day [DPDD]) among European-ancestry (EA) participants... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
In a previous study, ondansetron, a serotonin 5-HT receptor antagonist, reduced drinking intensity (drinks/drinking day [DPDD]) among European-ancestry (EA) participants with moderate-to-severe alcohol use disorder (AUD) and variants in genes encoding the serotonin transporter (SLC6A4) and 5-HT (HTR3A), and 5-HT (HTR3B) receptors. We tested whether (1) ondansetron reduces DPDD among individuals of either European or African ancestry (AA), and (2) that reductions in DPDD are greatest among ondansetron-treated individuals with population-specific combinations of genotypes at SLC6A4, HTR3A, and HTR3B.
METHODS
In this 16-week, double-blind, placebo-controlled, parallel-group clinical trial, adults with AUD were randomized to receive low-dose oral ondansetron (0.33 mg twice daily) or placebo stratified by "responsive" versus "nonresponsive" genotype defined using population-specific genotypes at the three genetic loci. Generalized estimating equation regression models and a modified intent-to-treat analysis were used to compare the treatment groups on the primary outcome-DPDD-and two secondary outcomes-heavy drinking days per week [HDD] and drinks per day [DPD] across the 16 weeks of treatment.
RESULTS
Of 296 prospective participants screened, 95 (58 EA and 37 AA) were randomized and received at least one dose of study medication. In the modified intent-to-treat analysis, the ondansetron group averaged 0.40 more DPDD (p = 0.51), 1.35 times as many HDD (p = 0.16), and 1.06 times as many DPD (p = 0.59) as the placebo group. There were no significant interactions with genotype. There were no study-related serious adverse events (AEs) and similar proportions of participants in the two treatment groups experienced AEs across organ systems.
CONCLUSIONS
We found no evidence that low-dose oral ondansetron is beneficial in the treatment of AUD, irrespective of genotype, thus failing to confirm prior study findings. However, the study was underpowered to identify medication by genotype interactions.
Topics: Adult; Humans; Ondansetron; Alcoholism; Serotonin Plasma Membrane Transport Proteins; Serotonin; Pharmacogenomic Testing; Prospective Studies; Double-Blind Method; Treatment Outcome
PubMed: 36055978
DOI: 10.1111/acer.14932 -
Anaesthesia Jan 1994The clinical development of ondansetron for the prevention and treatment of postoperative nausea and vomiting has been progressing for 5 years, and continues as new... (Review)
Review
The clinical development of ondansetron for the prevention and treatment of postoperative nausea and vomiting has been progressing for 5 years, and continues as new directions of research are being addressed. Large multicentre studies have demonstrated the efficacy of ondansetron in the prevention and treatment of postoperative nausea and vomiting, but no large comparator studies have been reported. Several studies are now being undertaken to compare ondansetron with other currently used antiemetics such as droperidol and metoclopramide, assessing efficacy, safety, pharmacoeconomic, and quality of life parameters. The majority of studies to date have been performed in gynaecological surgery patients receiving general anaesthesia--a population that experiences a high incidence of postoperative nausea and vomiting. Clinical development of ondansetron is therefore progressing to establish its efficacy in a wider surgical population, including paediatrics, the elderly, non-gynaecological surgery, and as retreatment in patients with failed prophylactic antiemetic therapy.
Topics: Adult; Aged; Analgesics, Opioid; Child; Drug Administration Schedule; Female; Humans; Nausea; Ondansetron; Postoperative Complications; Research Design; Vomiting
PubMed: 7907459
DOI: 10.1111/j.1365-2044.1994.tb03581.x -
British Journal of Clinical Pharmacology Feb 2021Changes in serotonergic sensory modulation associated with overexpression of 5-HT receptors in the central nervous system (CNS) have been implicated in the...
AIMS
Changes in serotonergic sensory modulation associated with overexpression of 5-HT receptors in the central nervous system (CNS) have been implicated in the pathophysiology of neuropathic pain after peripheral nerve damage. 5-HT receptor antagonists such as ondansetron can potentially alleviate neuropathic pain, but have limited effectiveness, due potentially to limited CNS access. However, there is currently limited information on CNS disposition of systemically-administered 5-HT receptor antagonists. This study evaluated the cerebrospinal fluid (CSF) disposition of ondansetron, as a surrogate of CNS penetration.
METHODS
Fifteen patients were given a single 16 mg intravenous 15 minute infusion of ondansetron, followed by serial blood and a single CSF sampling. Population pharmacokinetic (PK) modelling was implemented to describe the average and individual plasma and CSF profiles of ondansetron. A two-compartmental model was used to capture ondansetron plasma PK with a single CSF compartment to describe distribution to the CNS.
RESULTS
The individual model-estimated CSF to plasma partition coefficients of ondansetron were between 0.09 and 0.20. These values were mirrored in the calculated CSF penetration ratios, ranging from 0.08 to 0.26.
CONCLUSIONS
After intravenous administration, CSF concentrations of ondansetron were approximately 7-fold lower than those observed in the plasma. A model could be developed to describe individual CSF concentration-time profiles of ondansetron based on a single CSF data point. The low CSF penetration of ondansetron may explain its limited analgesic effectiveness, and affords an opportunity to explore enhancing its CNS penetration for targeting conditions such as neuropathic pain.
Topics: Administration, Intravenous; Humans; Infusions, Intravenous; Neuralgia; Ondansetron; Plasma
PubMed: 32495990
DOI: 10.1111/bcp.14412 -
Nigerian Journal of Clinical Practice Jul 2022This experimental study was designed to test the hypothesis that ondansetron, a selective 5-HT3 receptor antagonist, would decrease the duration of motor, sensory, and...
BACKGROUND AND AIMS
This experimental study was designed to test the hypothesis that ondansetron, a selective 5-HT3 receptor antagonist, would decrease the duration of motor, sensory, and proprioception blockade in a dose-dependent fashion in a bupivacaine-induced sciatic nerve blockade.
MATERIALS AND METHODS
Forty-nine male Wistar Albino rats who underwent unilateral sciatic nerve block were divided into seven groups with an equal number in each group. Group B: only perineural block (PB), Group BO200: PB and perineural 200 μg ondansetron, Group BO400: PB and perineural 400 μg ondansetron, Group BO800: PB and perineural 800 μg ondansetron, Group BO800IP: PB and intraperitoneal 800 μg ondansetron, Group O800: only perineural 800 μg ondansetron, Group S: sham-operated. The rats' motor, sensory, and proprioception functions were evaluated by a blinded investigator every 10 min until they returned to normal function. The recovery times of the motor, sensory, and proprioception functions were recorded and compared. All sciatic nerves were removed and examined by electron microscopy for neurotoxic signs.
RESULTS
In which sciatic nerve block was formed with bupivacaine, the duration of the motor, sensory, and proprioception functions blockade was decreased, and the duration to return to normal functions was significantly shortened at Group BO800 (p < 0.05). According to electron microscopy results, perineural 200 μg, 400 μg, and 800 μg ondansetron were not neurotoxic.
CONCLUSION
This is the first study showing that perineural ondansetron administration (800 μg dose) reverses the effect of the local anesthetics and shortens the duration of the motor, sensory, and proprioception functions blockade.
Topics: Animals; Bupivacaine; Male; Nerve Block; Ondansetron; Rats; Rats, Wistar; Sciatic Nerve
PubMed: 35859477
DOI: 10.4103/njcp.njcp_1804_21 -
Clinical Pharmacology and Therapeutics Aug 20175-hydroxytryptamine type 3 (5-HT) receptor antagonists are used in the prevention of chemotherapy- induced, radiation-induced and postoperative nausea and vomiting.... (Review)
Review
5-hydroxytryptamine type 3 (5-HT) receptor antagonists are used in the prevention of chemotherapy- induced, radiation-induced and postoperative nausea and vomiting. polymorphisms can influence the metabolism of some of these drugs (i.e. ondansetron and tropisetron) thereby affecting drug efficacy. We summarize evidence from the published literature supporting these associations and provide therapeutic recommendations for ondansetron and tropisetron based on genotype (updates at www.pharmgkb.org).
Topics: Antiemetics; Cytochrome P-450 CYP2D6; Drug-Related Side Effects and Adverse Reactions; Genetic Testing; Humans; Ondansetron; Pharmacogenetics; Polymorphism, Genetic; Postoperative Nausea and Vomiting; Radiotherapy; Serotonin 5-HT3 Receptor Agonists; Tropisetron
PubMed: 28002639
DOI: 10.1002/cpt.598