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Drugs in R&D Mar 2023Dopamine antagonists are the main pharmacological options to treat gastroparesis. The aim of this study was to conduct a systematic literature review (SLR) to evaluate... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Dopamine antagonists are the main pharmacological options to treat gastroparesis. The aim of this study was to conduct a systematic literature review (SLR) to evaluate the profile of adverse events (AEs) of dopamine antagonists used in the treatment of children and adults with gastroparesis.
METHODS
We searched EMBASE and MEDLINE up to March 25, 2021, for relevant clinical trials and observational studies. We conducted a proportional meta-analysis to estimate the pooled occurrence of AEs (%), with 95% confidence interval (CI), from arm-level data across studies and the comparative occurrence of AEs from placebo-controlled clinical trials (odds ratio [OR] with 95% CI).
RESULTS
We identified 28 studies assessing AEs experienced by patients treated for gastroparesis with domperidone and metoclopramide; 22 studies contributed data to the meta-analyses. Cardiovascular, neurological, and endocrine AEs were commonly observed, with point incidences varying from 1 to > 50%. Clinically important AEs, such as QTc prolongation, occurred in 5% of patients treated with domperidone (95% CI: 3.32-8.62). Restlessness, an extrapyramidal AE, occurred in 15% of patients (95% CI: 7.48-26.61) treated with metoclopramide, with a 7-fold increase compared with patients receiving placebo (OR: 7.72; 95% CI: 1.27-47.05). Variation in terminology to describe extrapyramidal events precluded further pooled analyses. Additional meta-analyses were not feasible due to discrepancies in the assessment and reporting of the AEs.
CONCLUSIONS
The evidence confirms concerns of cardiovascular, extrapyramidal, and endocrine AEs in patients with gastroparesis treated with domperidone and metoclopramide. Imprecise AE reporting limits firm interpretation and conclusions.
REGISTRATION
PROSPERO international prospective register of systematic reviews (registration number: CRD42021248888).
Topics: Adult; Child; Humans; Domperidone; Metoclopramide; Gastroparesis; Dopamine Antagonists
PubMed: 36749528
DOI: 10.1007/s40268-023-00413-x -
Journal of the American Board of Family... 2006Breast feeding is commonly accepted as the preferred method of infant nutrition for various reasons, both nutritional and emotional. For some who have become parents by... (Review)
Review
BACKGROUND
Breast feeding is commonly accepted as the preferred method of infant nutrition for various reasons, both nutritional and emotional. For some who have become parents by adoption, there is a strong desire to induce lactation for adoptive nursing.
METHODS
Information regarding adoptive nursing was initially obtained for the author's personal experience from searching the internet and speaking with other adoptive mothers. The medical literature was also searched through OVID/MEDLINE using pertinent terms, including induced lactation, adoptive nursing, domperidone, and metoclopramide.
RESULTS
Use of physiologic and pharmacologic methods can help an adoptive mother bring in a milk supply. The quantity may not be sufficient to entirely meet an infant's nutritional needs. However, for many the emotional benefits remain. There is some controversy surrounding the use of domperidone and metoclopramide for induced lactation. Herbals such as fenugreek have not been researched. Physicians can help their patients understand the current tools available to assist them with this unique endeavor.
Topics: Adoption; Breast Feeding; Domperidone; Dopamine Antagonists; Humans; Infant; Lactation; Metoclopramide; Milk, Human; Nipples
PubMed: 16809652
DOI: 10.3122/jabfm.19.4.374 -
Journal of Clinical Medicine Sep 2022The aims of gastroesophageal reflux disease (GERD) treatment are symptom relief and healing of oesophagitis. Besides proton pump inhibitors (PPIs), prokinetic agents are... (Review)
Review
Efficacy and Safety of Domperidone in Combination with Proton Pump Inhibitors in Gastroesophageal Reflux Disease: A Systematic Review and Meta-Analysis of Randomised Controlled Trials.
The aims of gastroesophageal reflux disease (GERD) treatment are symptom relief and healing of oesophagitis. Besides proton pump inhibitors (PPIs), prokinetic agents are also commonly prescribed to treat GERD. Domperidone, a well-known antiemetic, is an example of a prokinetic agent. It is a dopaminergic blocker that increases lower oesophagus sphincter pressure and activates gastric motility. We carried out a systematic review and meta-analysis to explore the benefits of domperidone in addition to PPI therapy for GERD. We searched for publications comparing PPI plus domperidone to PPI monotherapy in terms of symptom improvement in GERD (until 21 April 2022) on PubMed, Scopus, Google Scholar, Web of Science, Cochrane Library, WHO's International Clinical Studies Registry Platform, and ClinicalTrials.gov without restricting date, language, or study design. The protocol was registered in PROSPERO (CRD42021242076). This meta-analysis incorporated 11 studies with a total of 841 participants (419 in the PPI plus domperidone group and 422 in the PPI monotherapy group). The combination of a PPI and domperidone resulted in a significant reduction in global GERD symptoms. Adverse events associated with PPI plus domperidone treatment were similar to those associated with PPI monotherapy. In conclusion, the combination of domperidone and a PPI is generally safe and effective in treating GERD as compared with that of PPI alone.
PubMed: 36142915
DOI: 10.3390/jcm11185268 -
The Cochrane Database of Systematic... May 2021Orthostatic hypotension is an excessive fall in blood pressure (BP) while standing and is the result of a decrease in cardiac output or defective or inadequate...
BACKGROUND
Orthostatic hypotension is an excessive fall in blood pressure (BP) while standing and is the result of a decrease in cardiac output or defective or inadequate vasoconstrictor mechanisms. Fludrocortisone is a mineralocorticoid that increases blood volume and blood pressure. Fludrocortisone is considered the first- or second-line pharmacological therapy for orthostatic hypotension alongside mechanical and positional measures such as increasing fluid and salt intake and venous compression methods. However, there has been no Cochrane Review of the benefits and harms of this drug for this condition.
OBJECTIVES
To identify and evaluate the benefits and harms of fludrocortisone for orthostatic hypotension.
SEARCH METHODS
We searched the following databases on 11 November 2019: Cochrane Neuromuscular Specialised Register, CENTRAL, MEDLINE, Embase and CINAHL. We also searched trials registries.
SELECTION CRITERIA
We included all studies evaluating the benefits and harms of fludrocortisone compared to placebo, another drug for orthostatic hypotension, or studies without comparators, including randomized controlled trials (RCTs), quasi-RCTs and observational studies. We included studies in people with orthostatic hypotension due to a chronic peripheral neuropathy, a central autonomic neuropathy, or autonomic failure from other causes, but not medication-induced orthostatic hypotension or orthostatic hypotension from acute volume depletion or blood loss.
DATA COLLECTION AND ANALYSIS
We used Cochrane methodological procedures for most of the review. We developed and used a tool to prioritize observational studies that offered the best available evidence where there are gaps in the evidence from RCTs. We assessed the certainty of evidence for fludrocortisone versus placebo using GRADE.
MAIN RESULTS
We included 13 studies of 513 participants, including three cross-over RCTs and 10 observational studies (three cohort studies, six case series and one case-control study). The included RCTs were small (total of 28 participants in RCTs), short term (two to three weeks), only examined fludrocortisone for orthostatic hypotension in people with two conditions (diabetes and Parkinson disease), and had variable risk of bias (two had unclear risk of bias and one had low risk of bias). Heterogeneity in participant populations, comparators and outcome assessment methods prevented meta-analyses of the RCTs. We found very low-certainty evidence about the effects of fludrocortisone versus placebo on drop in BP in people with diabetes (-26 mmHg versus -39 mmHg systolic; -7 mmHg versus -11 mmHg diastolic; 1 cross-over study, 6 participants). For people with Parkinson disease, we found very-low certainty evidence about the effects of fludrocortisone on drop in BP compared to pyridostigmine (-14 mmHg versus -22.1 mmHg diastolic; P = 0.036; 1 cross-over study, 9 participants) and domperidone (no change after treatment in either group; 1 cross-over study, 13 participants). For orthostatic symptoms, we found very low-certainty evidence for fludrocortisone versus placebo in people with diabetes (4 out of 5 analyzed participants had improvements in orthostatic symptoms, 1 cross-over study, 6 participants), for fludrocortisone versus pyridostigmine in people with Parkinson disease (orthostatic symptoms unchanged; 1 cross-over study, 9 participants) or fludrocortisone versus domperidone (improvement to 6 for both interventions on the Composite Autonomic Symptom Scale-Orthostatic Domain (COMPASS-OD); 1 cross-over study, 13 participants). Evidence on adverse events was also very low-certainty in both populations, but indicated side effects were minimal. Observational studies filled some gaps in evidence by examining the effects in larger groups of participants, with more diverse conditions, over longer periods of time. One cohort study (341 people studied retrospectively) found fludrocortisone may not be harmful in the long term for familial dysautonomia. However, it is unclear if this translates to long-term improvements in BP drop or a meaningful improvement in orthostatic symptoms.
AUTHORS' CONCLUSIONS
The evidence is very uncertain about the effects of fludrocortisone on blood pressure, orthostatic symptoms or adverse events in people with orthostatic hypotension and diabetes or Parkinson disease. There is a lack of information on long-term treatment and treatment of orthostatic hypotension in other disease states. There is a need for standardized reporting of outcomes and for standardization of measurements of blood pressure in orthostatic hypotension.
Topics: Bias; Diabetes Mellitus; Domperidone; Dysautonomia, Familial; Fludrocortisone; Humans; Hypotension, Orthostatic; Observational Studies as Topic; Parkinson Disease; Pyridostigmine Bromide; Randomized Controlled Trials as Topic
PubMed: 34000076
DOI: 10.1002/14651858.CD012868.pub2 -
BMJ Clinical Evidence Oct 2008Gastro-oesophageal regurgitation is considered a problem if it is frequent, persistent, and associated with other symptoms such as increased crying, discomfort with... (Review)
Review
INTRODUCTION
Gastro-oesophageal regurgitation is considered a problem if it is frequent, persistent, and associated with other symptoms such as increased crying, discomfort with regurgitation, and frequent back arching. A cross-sectional survey of parents of 948 infants attending 19 primary care paediatric practices found that regurgitation of at least one episode a day was reported in 51% of infants aged 0-3 months.
METHODS AND OUTCOMES
We conducted a systematic review and aimed to answer the following clinical question: What are the effects of treatment for symptomatic gastro-oesophageal reflux? We searched: Medline, Embase, The Cochrane Library, and other important databases up to August 2007 (BMJ Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
RESULTS
We found 27 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
CONCLUSIONS
In this systematic review we present information relating to the effectiveness and safety of the following interventions: domperidone, feed thickeners in infants, H(2) antagonists, head elevated sleep positioning, left lateral or prone sleep positioning, metoclopramide, proton pump inhibitors, sodium alginate, surgery, soy formula with added fibre, and weight loss.
Topics: Acute Disease; Administration, Oral; Child; Cross-Sectional Studies; Domperidone; Gastroesophageal Reflux; Humans; Incidence; Infant; Metoclopramide; Proton Pump Inhibitors
PubMed: 19445794
DOI: No ID Found -
Ochsner Journal 2016Therapeutic approaches to addressing insufficient lactation are available but remain poorly understood. Current trends in maternal health, such as increasing rates of... (Review)
Review
BACKGROUND
Therapeutic approaches to addressing insufficient lactation are available but remain poorly understood. Current trends in maternal health, such as increasing rates of obesity, delayed age at childbearing, and high rates of cesarean section, may be associated with physiological challenges for lactation that cannot be managed by counseling alone. Women who have not had success with counseling alone, including adoptive mothers seeking to induce lactation, may use galactagogues (pharmaceutical and herbal compounds used to increase lactation). We present a review of selected studies of galactagogues and data indicating popular demand for such products.
METHODS
A systematic search was conducted for published studies on the use of galactagogues for breast-feeding. The following databases were searched: MEDLINE (PubMed), EBSCO (Academic Search Complete), and EMBASE. The search was conducted between July 15, 2015, and August 18, 2015; only English language articles were included, and we imposed no restrictions on publication date. Two authors independently reviewed the studies and extracted data.
RESULTS
Blinded, placebo-controlled clinical trials of 2 pharmaceutical galactagogues (domperidone and metoclopramide) and 5 popular herbal galactagogues (shatavari, fenugreek, silymarin, garlic, and malunggay) were identified. All of the studies identified for domperidone showed a significant difference in milk production between the treatment and placebo groups. Of the 6 trials of metoclopramide, only 1 study showed a significant difference in milk production compared to placebo. Results of the clinical trials on herbal galactagogues were mixed. Our review of the evidence for the efficacy of popular pharmaceutical and herbal galactagogues revealed a dearth of high-quality clinical trials and mixed results.
CONCLUSION
Health providers face the challenge of prescribing or recommending galactagogues without the benefit of robust evidence. Given the suboptimal rates of exclusive breast-feeding worldwide and the availability and demand for medical and herbal lactation therapies, controlled trials and analyses investigating these medicines are urgently warranted.
PubMed: 27999511
DOI: No ID Found -
The Cochrane Database of Systematic... Oct 2014Functional dyspepsia (FD) has been a worldwide complaint. More effective therapies are needed with fewer adverse effects than are seen with conventional medications.... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Functional dyspepsia (FD) has been a worldwide complaint. More effective therapies are needed with fewer adverse effects than are seen with conventional medications. Acupuncture, as a traditional therapeutic method, has been widely used for functional gastrointestinal disorders in the East. Manual acupuncture and electroacupuncture have been recognized treatments for FD, but to date, no robust evidence has been found for the effectiveness and safety of these interventions in the treatment of this condition.
OBJECTIVES
This review was conducted to assess the efficacy and safety of manual acupuncture and electroacupuncture in the treatment of FD.
SEARCH METHODS
Trials meeting the inclusion criteria were identified through electronic searches of the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, the Allied and Complementary Medicine Database (AMED), Chinese Biology Medicine Disc (CBMdisc), China National Knowledge Infrastructure (CNKI), the Wanfang Database, the VIP Database, and six trial registries. Handsearching was done to screen the reference sections of potential trials and reviews.
SELECTION CRITERIA
Randomized controlled trials (RCTs) were included if investigators reported efficacy and safety of manual acupuncture or electroacupuncture for patients with FD diagnosed by Rome II or Rome III criteria, compared with medications, blank control, or sham acupuncture.
DATA COLLECTION AND ANALYSIS
Data were extracted by independent review authors. Study limitations were assessed by using the tool of The Cochrane Collabration for assessing risk of bias. For dichotomous data, risk ratios (RRs) and 95% confidence intervals (95% CIs) would be applied, and for continuous data, mean differences (MDs) and 95% CIs. A fixed-effect model was applied in the meta-analysis, or a descriptive analysis was performed. The quality of evidence for the outcome measure was assessed by the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methods.
MAIN RESULTS
Seven studies were included in the review, involving 542 participants with FD (212 males and 330 females). These studies generally had an unclear risk of bias based on inadequate descriptions of allocation concealment and a high risk of bias based on lack of blinding. None of the studies reported on outcomes of the Functional Digestive Disorder Quality of Life questionnaire (FDDQL), the Satisfaction With Dyspepsia Related Health scale (SODA), the Digestive Health Status Instrument (DHSI), or effective/inefficient rate and symptom recurrence six months from completion of acupuncture treatment.Four RCTs of acupuncture versus medications (cisapride, domperidone, and itopride) were included in the review. No statistically significant difference was noted in the reduction in FD symptom scores and the frequency of FD attack by manual acupuncture, manual-electroacupuncture, or electroacupuncture compared with medications. In three trials of acupuncture versus sham acupuncture, all descriptive or quantitative analysis results implied that acupuncture could improve FD symptom scores and scores on the Neck Disability Index (NDI), the 36-Item Short Form Health Survey (SF-36), the Self-Rating Anxiety Scale (SAS), and the Self-Rating Depression Scale (SDS) more or as significantly as sham acupuncture. With regard to adverse effects, acupuncture was superior to cisapride treatment (one study; all minor events), but no statistically significant difference was reported between acupuncture and sham acupuncture. No adverse effects data were reported in studies examining manual acupuncture versus domperidone, manual-electroacupuncture versus domperidone, or electroacupuncture versus itopride.Nevertheless, all evidence was of low or very low quality. The body of evidence identified cannot yet permit a robust conclusion regarding the efficacy and safety of acupuncture for FD.
AUTHORS' CONCLUSIONS
It remains unknown whether manual acupuncture or electroacupuncture is more effective or safer than other treatments for patients with FD.
Topics: Acupuncture Therapy; Benzamides; Benzyl Compounds; Cisapride; Domperidone; Dyspepsia; Electroacupuncture; Female; Gastrointestinal Agents; Humans; Male; Randomized Controlled Trials as Topic
PubMed: 25306866
DOI: 10.1002/14651858.CD008487.pub2 -
Biomolecules & Therapeutics Nov 2023The lack of molecular targets hampers the treatment of triple-negative breast cancer (TNBC). In this study, we determined the cytotoxicity of domperidone, a dopamine D2...
The lack of molecular targets hampers the treatment of triple-negative breast cancer (TNBC). In this study, we determined the cytotoxicity of domperidone, a dopamine D2 receptor (DRD2) antagonist in human TNBC BT-549 and CAL-51 cells. Domperidone inhibited cell growth in a dose- and time-dependent manner. The annexin V/propidium iodide staining showed that domperidone induced apoptosis. The domperidone-induced apoptosis was accompanied by the generation of mitochondrial superoxide and the down-regulation of cyclins and CDKs. The apoptotic effect of domperidone on TNBC cells was prevented by pre-treatment with Mito-TEMPO, a mitochondria-specific antioxidant. The prevention of apoptosis with Mito-TEMPO even at concentrations as low as 100 nM, implies that the generation of mitochondrial ROS mediated the domperidone-induced apoptosis. Immunoblot analysis showed that domperidone-induced apoptosis occurred through the down-regulation of the phosphorylation of JAK2 and STAT3. Moreover, domperidone downregulated the levels of D2-like dopamine receptors including DRD2, regardless of their mRNA levels. Our results support further development of DRD2 antagonists as potential therapeutic strategy treating TNBC.
PubMed: 37899746
DOI: 10.4062/biomolther.2023.173 -
CMAJ : Canadian Medical Association... Sep 1986Domperidone is a dopamine antagonist that has recently been released in Canada. Unlike metoclopramide hydrochloride, the other available dopamine antagonist, it does not... (Clinical Trial)
Clinical Trial Review
Domperidone is a dopamine antagonist that has recently been released in Canada. Unlike metoclopramide hydrochloride, the other available dopamine antagonist, it does not readily enter the central nervous system. Domperidone acts as both an antiemetic and an upper gastrointestinal tract prokinetic agent. It is rapidly absorbed after oral administration, and few side effects have been reported. Domperidone has been approved for use in Canada for the symptomatic management of upper gastrointestinal tract motility disorders and to prevent gastrointestinal symptoms associated with the use of dopamine agonist agents in Parkinson's disease. The pharmacologic features, indications and side effects of domperidone are reviewed.
Topics: Administration, Oral; Adult; Child; Clinical Trials as Topic; Domperidone; Dopamine Antagonists; Dyspepsia; Gastroesophageal Reflux; Gastrointestinal Motility; Headache; Humans; Infant; Migraine Disorders; Nausea; Parkinson Disease; Stomach Diseases; Tablets; Vomiting
PubMed: 3527396
DOI: No ID Found -
Australian Family Physician Sep 2006Many breastfeeding women have concerns about their milk supply; 'not enough milk' is the most common reason women give for stopping breastfeeding, however their concern... (Review)
Review
BACKGROUND
Many breastfeeding women have concerns about their milk supply; 'not enough milk' is the most common reason women give for stopping breastfeeding, however their concern is often unwarranted.
OBJECTIVE
The article describes the process of history taking and examination of mother and infant to determine if the mother's milk supply is adequate, the causes of insufficient milk supply, and possible investigations and management.
DISCUSSION
Insufficient milk supply may be secondary to maternal conditions such as postpartum haemorrhage or breast reduction surgery, or infant factors such as tongue-tie or ill health. In many cases, milk supply can be increased by frequent, regular milk removal. Medication to increase milk supply (galactogogues) such as domperidone, may also play a role. General practitioners can provide reassurance if milk supply is adequate, or can assist in resolving the problem if milk supply is low.
Topics: Breast Feeding; Female; Humans; Infant; Infant Care; Infant, Newborn; Lactation; Mammary Glands, Human; Medical History Taking; Milk, Human; Physical Examination
PubMed: 16969436
DOI: No ID Found