-
Journal of Clinical Medicine Mar 2023In patients with chronic idiopathic diarrhea resistant to standard treatment, opioids are often used as rescue therapy. This systematic review investigated opioid... (Review)
Review
In patients with chronic idiopathic diarrhea resistant to standard treatment, opioids are often used as rescue therapy. This systematic review investigated opioid effects on gut function in chronic diarrhea. PubMed and Embase were searched regarding effects of opioid agonists on the gastrointestinal tract in humans with chronic or experimentally induced diarrhea. A total of 1472 relevant articles were identified and, after thorough evaluation, 11 clinical trials were included. Generally, studies reported a reduction in stool frequency and an increase in transit time during treatment with the opioid receptor agonists loperamide, asimadoline, casokefamide, and codeine compared with placebo. Loperamide and diphenoxylate significantly improved stool consistency compared with placebo, whereas asimadoline showed no such effects. Compared with placebo, loperamide treatment caused less abdominal pain and urgency. Asimadoline showed no significant subjective improvements, but fedotozine was superior to placebo in reducing abdominal pain and bloating in selected patients. Only two relevant studies were published within the last 20 years, and standardized endpoint measures are lacking. Most trials included few participants, and further evidence is needed from larger, prospective studies. Likewise, consensus is needed to standardize endpoints for stool frequency, transit time, and consistency to conduct future meta-analyses on opioids in management of chronic idiopathic diarrhea.
PubMed: 37048572
DOI: 10.3390/jcm12072488 -
The Cochrane Database of Systematic... May 2015Agitation is a common experience for people living with dementia, particularly as day-to-day function and cognition start to decline more. At the present time there are... (Review)
Review
BACKGROUND
Agitation is a common experience for people living with dementia, particularly as day-to-day function and cognition start to decline more. At the present time there are limited pharmacological options for relieving agitation and little is known about the safety and efficacy of opioid drugs in this setting.
OBJECTIVES
To determine the clinical efficacy and safety of opioids for agitation in people with dementia.
SEARCH METHODS
We searched ALOIS, the Cochrane Dementia and Cognitive Improvement Group Specialized Register, on 13 June 2014 using the terms: narcotic OR opioid OR opium OR morphine OR buprenorphine OR codeine OR dextromoramide OR diphenoxylate OR dipipanone OR dextropropoxyphene OR propoxyphene OR diamorphine OR dihydrocodeine OR alfentanil OR fentanyl OR remifentanil OR meptazinol OR methadone OR nalbuphine OR oxycodone OR papaveretum OR pentazocine OR meperidine OR pethidine OR phenazocine OR hydrocodone OR hydromorphone OR levorphanol OR oxymorphone OR butorphanol OR dezocine OR sufentanil OR ketobemidone.ALOIS contains records of clinical trials identified from monthly searches of a number of major healthcare databases such as MEDLINE, EMBASE and PscyINFO, as well as numerous trial registries and grey literature sources.
SELECTION CRITERIA
Randomised, controlled trials of opioids compared to placebo for agitation in people with dementia.
DATA COLLECTION AND ANALYSIS
Two authors independently assessed the studies identified by the search against the inclusion criteria.
MAIN RESULTS
There are currently no completed randomised, placebo controlled trials of opioids for agitation in dementia. There are two potentially relevant trials still in progress.
AUTHORS' CONCLUSIONS
We found insufficient evidence to establish the clinical efficacy and safety of opioids for agitation in people with dementia. There remains a lack of data to determine if or when opioids either relieve or exacerbate agitation. More evidence is needed to guide the effective, appropriate and safe use of opioids in dementia.
Topics: Analgesics, Opioid; Dementia; Humans; Psychomotor Agitation
PubMed: 25972091
DOI: 10.1002/14651858.CD009705.pub2 -
The Cochrane Database of Systematic... Jun 2013Faecal incontinence (leakage of bowel motions or stool) is a common symptom which causes significant distress and reduces quality of life. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Faecal incontinence (leakage of bowel motions or stool) is a common symptom which causes significant distress and reduces quality of life.
OBJECTIVES
To assess the effects of drug therapy for the treatment of faecal incontinence. In particular, to assess the effects of individual drugs relative to placebo or other drugs, and to compare drug therapy with other treatment modalities.
SEARCH METHODS
We searched the Cochrane Incontinence Group Specialised Register of Trials, which contains trials identified from the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and MEDLINE in process, and handsearching of journals and conference proceedings (searched 21 June 2012) and the reference lists of relevant articles.
SELECTION CRITERIA
All randomised or quasi-randomised controlled trials were included in this systematic review.
DATA COLLECTION AND ANALYSIS
Two review authors independently screened abstracts, extracted data and assessed risk of bias of the included trials.
MAIN RESULTS
Sixteen trials were identified, including 558 participants. Eleven trials were of cross-over design. Eleven trials included only people with faecal incontinence related to liquid stool (either chronic diarrhoea, following ileoanal pouch or rectal surgery, or due to use of a weight-reducing drug). Two trials were amongst people with weak anal sphincters, one in participants with faecal impaction and bypass leakage, and one in geriatric patients. In one trial there was no specific cause for faecal incontinence.Seven trials tested anti-diarrhoeal drugs to reduce faecal incontinence and other bowel symptoms (loperamide, diphenoxylate plus atropine, and codeine). Six trials tested drugs that enhance anal sphincter function (phenylepinephrine gel and sodium valproate). Two trials evaluated osmotic laxatives (lactulose) for the treatment of faecal incontinence associated with constipation in geriatric patients. One trial assessed the use of zinc-aluminium ointment for faecal incontinence. No studies comparing drugs with other treatment modalities were identified.There was limited evidence that antidiarrhoeal drugs and drugs that enhance anal sphincter tone may reduce faecal incontinence in patients with liquid stools. Loperamide was associated with more adverse effects (such as constipation, abdominal pain, diarrhoea, headache and nausea) than placebo. However, the dose may be titrated to the patient's symptoms to minimise side effects while achieving continence. The drugs acting on the sphincter sometimes resulted in local dermatitis, abdominal pain or nausea. Laxative use in geriatric patients reduced faecal soiling and the need for help from nurses.Zinc-aluminium ointment was associated with improved quality of life, with no reported adverse effects. However, the observed improvement in quality of life was seen in the placebo group as well as the treatment group.It should be noted that all the included trials in this review had small sample sizes and short duration of follow-up. 'Risk of bias' assessment was unclear for most of the domains as there was insufficient information. There were no data suitable for meta-analysis.
AUTHORS' CONCLUSIONS
The small number of trials identified for this review assessed several different drugs in a variety of patient populations. The focus of most of the included trials was on the treatment of diarrhoea, rather than faecal incontinence. There is little evidence to guide clinicians in the selection of drug therapies for faecal incontinence. Larger, well-designed controlled trials, which use the recommendations and principles set out in the CONSORT statement, and include clinically important outcome measures, are required.
Topics: Adult; Antidiarrheals; Diarrhea; Epinephrine; Fecal Incontinence; Gastrointestinal Agents; Humans; Lactulose; Randomized Controlled Trials as Topic; Valproic Acid; Zinc Compounds
PubMed: 23757096
DOI: 10.1002/14651858.CD002116.pub2 -
The Cochrane Database of Systematic... Oct 2008AIDS-related diarrhoea is a common cause of morbidity and mortality in HIV positive individuals, especially in the sub-Saharan Africa where 70% of deaths from HIV occur.... (Review)
Review
BACKGROUND
AIDS-related diarrhoea is a common cause of morbidity and mortality in HIV positive individuals, especially in the sub-Saharan Africa where 70% of deaths from HIV occur. It often compromises quality of life both in those receiving antiretroviral therapy (ART) and the ART naive. Empirical antidiarrhoeal treatment may be required in about 50% of cases which are non-pathogenic or idiopathic and in cases resulting from antiretroviral therapy. Antimotility agents (Loperamide, Diphenoxylate, Codeine) and adsorbents (Bismuth Subsalicylate, Kaolin/Pectin, Attapulgite) are readily available, and have been found to be useful in this condition and so, are often used. Antimotilitics are opioids, decreasing stool output by reducing bowel activity thereby increasing fecal transit time in the gut, promoting fluid and electrolyte retention while adsorbents act by binding to fluids, toxins and other substances to improve stool consistency and eliminate the toxins. Due to its potential impact on the management of chronic diarrhoea in persons with HIV/AIDS, we reviewed the effectiveness of antimotility agents in controlling chronic diarrhoea in immunocompromised states caused by HIV/AIDS.
OBJECTIVES
To assess the effectiveness of antimotility agents in controlling chronic diarrhoea in people with HIV/AIDS.
SEARCH STRATEGY
We searched Medline, EMBASE, the Cochrane Controlled Trials Register, the Cochrane HIV/AIDS Register and AIDSearch databases in November 2006. We also contacted WHO, CDC, pharmaceutical companies and experts in the field for information on previous or on-going trials and checked reference list from retrieved studies, irrespective of language and publication status.
SELECTION CRITERIA
Randomised controlled trials comparing an antimotility agent or an adsorbent with another antimotility agent, placebo, an adsorbent or no treatment in children and adults diagnosed with HIV and presenting with diarrhoea of three or more weeks duration.
DATA COLLECTION AND ANALYSIS
Two authors independently undertook study selection and examined full articles of potentially eligible studies.
MAIN RESULTS
One trial was found assessing the use of an adsorbent (attapulgite) compared to a placebo for chronic diarrhoea in people with HIV/AIDS. It included 91 adults (Aged 18 to 60), diagnosed with AIDS and experiencing diarrhoea for at least 7 days. There was no evidence that attapulgite is superior to placebo in controlling diarrhoea by reducing stool frequency and normalising stool consistency on days 1 (0.34 (95% CI 0.01 - 8.15)), 3 (1.35 (95% CI 0.51 - 3.62)) and 5 (1.74 (95% CI 0.89 - 3.38)). This was a small trial and may not have had enough power to show evidence of effects. Five deaths were reported which was not classified according to the arms of the study.Studies assessing the use of antimotility agents were not found.
AUTHORS' CONCLUSIONS
This review highlights the absence of evidence for the use of antimotility agents and adsorbents in controlling diarrhoea in people with HIV/AIDS. While no trials assessing the use of Antimotilitics were found, the retrieved study showed that attapulgite was not better than placebo in controlling diarrhoea in HIV/AIDS patients . For optimum patient care, these agents can still be used, with greater emphasis placed on adjunct therapies like massive fluid replacement while evidence for practice is awaited from further studies and reviews.
Topics: Acquired Immunodeficiency Syndrome; Adult; Antidiarrheals; Chronic Disease; Diarrhea; Gastrointestinal Transit; HIV Infections; Humans; Immunocompromised Host; Magnesium Compounds; Silicon Compounds
PubMed: 18843696
DOI: 10.1002/14651858.CD005644.pub2 -
Schmerz (Berlin, Germany) Apr 2013Diarrhea is a distressing symptom which limits the quality of life in patients receiving palliative care and is associated with high morbidity and mortality. In patients... (Comparative Study)
Comparative Study Review
Diarrhea is a distressing symptom which limits the quality of life in patients receiving palliative care and is associated with high morbidity and mortality. In patients with AIDS, it is a more common problem than for other entities (e.g., cancer). Loperamide is considered the first choice medication for the symptomatic treatment of diarrhea. This literature review examines the efficacy of loperamide in the symptomatic treatment of diarrhea in palliative care. Two databases (Medline and Embase) were searched through June 2012. A total of 286 studies were identified, but only 7 met the inclusion criteria (1 cohort and 6 experimental studies) in which loperamide (alone or in combination) was tested. There is a lack of significant studies which investigate the efficacy of loperamide in the symptomatic treatment of diarrhea. Two trials indicated superiority of loperamide over placebo. In comparison with octreotide, the results were contradictory. The combination of acetorphan with loperamide was more effective than acetorphan alone, but the combination of loperamide with diphenoxylate was inferior to octreotide. The identified studies revealed methodical problems. A definite recommendation for administration of loperamide can, therefore, not be derived from this work.The English full-text version of this article is available at SpringerLink (under "Supplemental").
Topics: Acquired Immunodeficiency Syndrome; Antidiarrheals; Controlled Clinical Trials as Topic; Diarrhea; Diphenoxylate; Drug Therapy, Combination; Humans; Loperamide; Octreotide; Palliative Care; Thiorphan
PubMed: 23475156
DOI: 10.1007/s00482-013-1296-z -
The Cochrane Database of Systematic... 2003Faecal incontinence is a common symptom which causes significant distress and reduction in quality of life. Available treatment options for faecal incontinence include... (Review)
Review
BACKGROUND
Faecal incontinence is a common symptom which causes significant distress and reduction in quality of life. Available treatment options for faecal incontinence include conservative treatments (biofeedback, pelvic floor muscle training, dietary manipulation or drug therapy) or surgical treatments (e.g. sphincter repair, post anal repair, neosphincter). Drug treatment is often given either alone or in combination with other treatment modalities.
OBJECTIVES
To assess the effects of drug therapy for the treatment of faecal incontinence. In particular, to assess the effects of individual drugs relative to placebo or other drugs, and to compare drug therapy with other treatment modalities.
SEARCH STRATEGY
We searched the Cochrane Incontinence Group trials register (January 2003) and the reference lists of relevant articles. Date of the most recent search: January 2003.
SELECTION CRITERIA
All randomised or quasi-randomised controlled trials of the use of pharmacological agents for the treatment of faecal incontinence in adults.
DATA COLLECTION AND ANALYSIS
Working independently, reviewers selected studies from the literature, assessed the methodological quality of each trial, and extracted data.
MAIN RESULTS
Eleven trials were identified for inclusion in this review. Nine trials were of cross-over design. Seven trials included only people with faecal incontinence related to liquid stool (either chronic diarrhoea or following ileoanal pouch surgery). Three trials (total 58 participants) compared topical phenylephrine gel with placebo. Two trials (56 participants) compared loperamide with placebo. One trial (11 participants) compared loperamide oxide with placebo. One trial (15 participants) compared diphenoxylate plus atropine with placebo. One trial (17 participants) compared sodium valproate with placebo. One trial (30 participants) compared loperamide with codeine with diphenoxylate plus atropine. Two further trials (total 265 participants) assessed the use of lactulose in elderly people.No studies comparing drugs with other treatment modalities were identified. There was limited evidence that antidiarrhoeal drugs and drugs which enhance anal sphincter tone may reduce faecal incontinence in patients with liquid stools. However, the trials were small and of short duration.
REVIEWER'S CONCLUSIONS
The small number of trials identified for this review assessed several different drugs in a variety of patient populations. The focus of most of the included trials was on the treatment of diarrhoea, rather than faecal incontinence. There is little evidence to guide clinicians in the selection of drug therapies for faecal incontinence. Larger, well-designed controlled trials, which include clinically important outcome measures, are required.
Topics: Adult; Diarrhea; Fecal Incontinence; Humans; Randomized Controlled Trials as Topic
PubMed: 12917921
DOI: 10.1002/14651858.CD002116 -
The Journal of Trauma and Acute Care... Oct 2019Acute noninfectious diarrhea is a common phenomenon in intensive care unit patients. Multiple treatments are suggested but the most effective management is unknown. A...
Antimotility agents for the treatment of acute noninfectious diarrhea in critically ill patients: A practice management guideline from the Eastern Association for the Surgery of Trauma.
BACKGROUND
Acute noninfectious diarrhea is a common phenomenon in intensive care unit patients. Multiple treatments are suggested but the most effective management is unknown. A working group of the Eastern Association for the Surgery of Trauma, aimed to evaluate the effectiveness of loperamide, diphenoxylate/atropine, and elemental diet on acute noninfectious diarrhea in critically ill adults and to develop recommendations applicable to daily clinical practice.
METHODS
The literature search identified 11 randomized controlled trials (RCT) appropriate for inclusion. The Grading of Recommendations Assessment, Development, and Evaluation methodology was applied to evaluate the effect of loperamide, diphenoxylate/atropine, and elemental diet on the resolution of noninfectious diarrhea in critically ill adults based on selected outcomes: improvement in clinical diarrhea, fecal frequency, time to the diarrhea resolution, and hospital length of stay.
RESULTS
The level of evidence was assessed as very low. Analyses of 10 RCTs showed that loperamide facilitates resolution of diarrhea. Diphenoxylate/atropine was evaluated in three RCTs and was as effective as loperamide and more effective than placebo. No studies evaluating elemental diet as an intervention in patients with diarrhea were found.
CONCLUSION
Loperamide and diphenoxylate/atropine are conditionally recommended to be used in critically ill patients with acute noninfectious diarrhea.
LEVEL OF EVIDENCE
Systematic Review/Guidelines, level III.
Topics: Adult; Antidiarrheals; Critical Illness; Diarrhea; Diet Therapy; Diphenoxylate; Gastrointestinal Motility; Humans; Loperamide; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 31574060
DOI: 10.1097/TA.0000000000002449