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BMJ Clinical Evidence Jul 2010Although there are defined criteria for the diagnosis of constipation, in practice, diagnostic criteria are less rigid, and depend in part on the perception of normal... (Review)
Review
INTRODUCTION
Although there are defined criteria for the diagnosis of constipation, in practice, diagnostic criteria are less rigid, and depend in part on the perception of normal bowel habit. Constipation is highly prevalent, with approximately 12 million general practitioner prescriptions for laxatives in England in 2001.
METHODS AND OUTCOMES
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of non-drug interventions, bulk-forming laxatives, faecal softeners, stimulant laxatives, osmotic laxatives, prostaglandin derivatives, and 5-HT4 agonists in adults with idiopathic chronic constipation? We searched: Medline, Embase, The Cochrane Library, and other important databases up to October 2009 (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 51systematic 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: arachis oil, biofeedback, bisacodyl, cascara, docusate, exercise, glycerol/glycerine suppositories, high-fibre diet, increasing fluids, ispaghula husk, lactitol, lactulose, lubiprostone, macrogols (polyethylene glycols), magnesium salts, methylcellulose, paraffin, phosphate enemas, seed oils, senna, sodium citrate enemas, prucalopride, and sterculia.
Topics: Administration, Oral; Adult; Constipation; Defecation; Humans; Lactulose; Laxatives; Treatment Outcome
PubMed: 21418672
DOI: No ID Found -
The American Journal of Gastroenterology Jun 2021Constipation is commonly treated with over-the-counter (OTC) products whose efficacy and safety remain unclear. We performed a systematic review of OTC therapies for...
INTRODUCTION
Constipation is commonly treated with over-the-counter (OTC) products whose efficacy and safety remain unclear. We performed a systematic review of OTC therapies for chronic constipation and provide evidence-based recommendations.
METHODS
We searched PubMed and Embase for randomized controlled trials of ≥4-week duration that evaluated OTC preparations between 2004 and 2020. Studies were scored using the US Preventive Services Task Force criteria (0-5 scale) including randomization, blinding, and withdrawals. The strengths of evidence were adjudicated within each therapeutic category, and recommendations were graded (A, B, C, D, and I) based on the level of evidence (level I, good; II, fair; or III, poor).
RESULTS
Of 1,297 studies identified, 41 met the inclusion criteria. There was good evidence (grade A recommendation) for the use of the osmotic laxative polyethylene glycol (PEG) and the stimulant senna; moderate evidence (grade B) for psyllium, SupraFiber, magnesium salts, stimulants (bisacodyl and sodium picosulfate), fruit-based laxatives (kiwi, mango, prunes, and ficus), and yogurt with galacto-oligosaccharide/prunes/linseed oil; and insufficient evidence (grade I) for polydextrose, inulin, and fructo-oligosaccharide. Diarrhea, nausea, bloating, and abdominal pain were common adverse events, but no serious adverse events were reported.
DISCUSSION
The spectrum of OTC products has increased and quality of evidence has improved, but methodological issues including variability in study design, primary outcome measures, trial duration, and small sample sizes remain. We found good evidence to recommend polyethylene glycol or senna as first-line laxatives and moderate evidence supporting fiber supplements, fruits, stimulant laxatives, and magnesium-based products. For others, further validation with more rigorously designed studies is warranted.
Topics: Bisacodyl; Cathartics; Chronic Disease; Citrates; Constipation; Defecation; Fruit; Gastrointestinal Agents; Glucans; Humans; Inulin; Laxatives; Magnesium; Nonprescription Drugs; Oligosaccharides; Organometallic Compounds; Picolines; Polyethylene Glycols; Psyllium; Senna Extract; Yogurt
PubMed: 33767108
DOI: 10.14309/ajg.0000000000001222 -
Gut Sep 2017To compare efficacy of pharmacotherapies for chronic idiopathic constipation (CIC) based on comparisons to placebo using Bayesian network meta-analysis. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To compare efficacy of pharmacotherapies for chronic idiopathic constipation (CIC) based on comparisons to placebo using Bayesian network meta-analysis.
DATA SOURCES
We conducted searches (inception to May 2015) of MEDLINE, EMBASE, Scopus and Cochrane Central, as well as original data from authors or drug companies for the medications used for CIC.
STUDY SELECTION
Phase IIB and phase III randomised, placebo-controlled trials (RCT) of ≥4 weeks' treatment for CIC in adults with Rome II or III criteria for functional constipation; trials included at least one of four end points.
DATA EXTRACTION AND SYNTHESIS
Two investigators independently evaluated all full-text articles that met inclusion criteria and extracted data for primary and secondary end points, risk of bias and quality of evidence.
OUTCOMES
Primary end points were ≥3 complete spontaneous bowel movements (CSBM)/week and increase over baseline by ≥1 CSBM/week. Secondary end points were change from baseline (Δ) in the number of SBM/week and Δ CSBM/week.
RESULTS
Twenty-one RCTs (9189 patients) met inclusion and end point criteria: 9 prucalopride, 3 lubiprostone, 3 linaclotide, 2 tegaserod, 1 each velusetrag, elobixibat, bisacodyl and sodium picosulphate (NaP). All prespecified end points were unavailable in four polyethylene glycol studies. Bisacodyl, NaP, prucalopride and velusetrag were superior to placebo for the ≥3 CSBM/week end point. No drug was superior at improving the primary end points on network meta-analysis. Bisacodyl appeared superior to the other drugs for the secondary end point, Δ in number of SBM/week.
CONCLUSIONS
Current drugs for CIC show similar efficacy. Bisacodyl may be superior to prescription medications for Δ in the number of SBM/week in CIC.
Topics: Azabicyclo Compounds; Benzofurans; Bisacodyl; Chronic Disease; Citrates; Constipation; Defecation; Drug Monitoring; Gastrointestinal Agents; Humans; Organometallic Compounds; Picolines; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 27287486
DOI: 10.1136/gutjnl-2016-311835 -
Efficacy of drugs in chronic idiopathic constipation: a systematic review and network meta-analysis.The Lancet. Gastroenterology &... Nov 2019There are several drugs available for the treatment of chronic idiopathic constipation, but their relative efficacy is unclear because there have been no head-to-head... (Meta-Analysis)
Meta-Analysis
BACKGROUND
There are several drugs available for the treatment of chronic idiopathic constipation, but their relative efficacy is unclear because there have been no head-to-head randomised controlled trials. We did a network meta-analysis to compare the efficacy of these therapies in patients with chronic idiopathic constipation.
METHODS
We searched Medline, Embase, Embase Classic, and the Cochrane Central Register of Controlled Trials for randomised controlled trials published from inception to week 3 June, 2019, to identify randomised controlled trials assessing the efficacy of drugs (osmotic or stimulant laxatives, elobixibat, linaclotide, lubiprostone, mizagliflozin, naronapride, plecanatide, prucalopride, tegaserod, tenapanor, or velusetrag) in adults with chronic idiopathic constipation. Participants had to be treated for a minimum of 4 weeks, and we extracted data for all endpoints preferentially at 4 weeks, 12 weeks, or both. Trials included in the analysis reported a dichotomous assessment of overall response to therapy (response or no response to therapy). We pooled the data using a random effects model, and reported efficacy and safety of all treatments as a pooled relative risk (RR) with 95% CIs to summarise the effect of each comparison tested. To rank treatments, we used P-scores, which measure the extent of certainty that a treatment is better than another treatment, averaged over all competing treatments.
FINDINGS
We identified 33 eligible randomised controlled trials of drugs, comprising 17 214 patients. Based on an endpoint of failure to achieve three or more complete spontaneous bowel movements (CSBMs) per week, the stimulant diphenyl methane laxatives bisacodyl and sodium picosulfate, at a dose of 10 mg once daily, were ranked first at 4 weeks (RR 0·55, 95% CI 0·48-0·63, P-score 0·99), and prucalopride 2 mg once daily ranked first at 12 weeks (0·82, 0·78-0·86, P-score 0·96). When response to therapy was defined as falilure to achieve an increase of one or more CSBM per week from baseline, diphenyl methane laxatives at a dose of 10 mg once daily ranked first at 4 weeks (0·44, 0·37-0·54, P-score 0·99), with prucalopride 4 mg once daily ranked first at 12 weeks (0·74, 0·66-0·83, P-score 0·79), although linaclotide 290 μg once daily and prucalopride 2 mg once daily had similar efficacy (P-scores of 0·76 and 0·71, respectively). Bisacodyl ranked last in terms of safety for total number of adverse events and abdominal pain (P-score 0·08).
INTERPRETATION
Almost all drugs studied were superior to placebo, according to either failure to achieve three or more CSBMs per week or or failure to achieve an increase of one or more CSBM per week over baseline. Although diphenyl methane laxatives ranked first at 4 weeks, patients with milder symptoms might have been included in these trials. Prucalopride ranked first at 12 weeks, and many of the included trials recruited patients who previously did not respond to laxatives, suggesting that this drug is likely to be the most efficacious for patients with chronic idiopathic constipation. However, because treatment duration in most trials was 4-12 weeks, the long-term relative efficacy of these drugs is unknown.
FUNDING
None.
Topics: Constipation; Humans; Laxatives; Randomized Controlled Trials as Topic
PubMed: 31474542
DOI: 10.1016/S2468-1253(19)30246-8 -
Journal of the American Association of... Sep 2022Chronic constipation is a common gastrointestinal condition, and most individuals self-treat with multiple over-the-counter (OTC) laxatives prior to consulting a health...
Chronic constipation is a common gastrointestinal condition, and most individuals self-treat with multiple over-the-counter (OTC) laxatives prior to consulting a health care provider. This brief report is a synopsis of an updated systematic review the authors conducted of published data on the efficacy and safety of OTC treatments to provide evidence-based recommendations. After applying the selection criteria, 41 randomized controlled clinical trials of ≥ 4-week duration were identified and analyzed. Standardized definitions of constipation were applied across these studies; however, definitions for stool frequency and consistency varied. Overall, the short- and long-term efficacy of polyethylene glycol-based preparations and senna were supported by good (grade A) evidence suggesting their use as first-line laxatives. Modest evidence (grade B) supported the use of other agents including the stimulants bisacodyl and sodium picosulfate, fiber, fruit-based laxatives, and magnesium oxide. Additional evidence from rigorously designed studies is needed to support the use of other options for chronic constipation. The OTC products studied were generally well tolerated with common adverse effects being abdominal pain, cramping, bloating, diarrhea, and nausea.
Topics: Constipation; Dietary Fiber; Humans; Laxatives; Nonprescription Drugs; Polyethylene Glycols; Treatment Outcome
PubMed: 35943487
DOI: 10.1097/JXX.0000000000000760 -
BMJ Clinical Evidence Aug 2007Although there are defined criteria for the diagnosis of constipation, in practice, diagnostic criteria are less rigid, and in part depend on the perception of normal... (Review)
Review
INTRODUCTION
Although there are defined criteria for the diagnosis of constipation, in practice, diagnostic criteria are less rigid, and in part depend on the perception of normal bowel habit. Constipation is highly prevalent, with approximately 12 million general practitioner prescriptions for laxatives in England in 2001.
METHODS AND OUTCOMES
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of non-drug interventions, and of other interventions, in adults with idiopathic chronic constipation? We searched: Medline, Embase, The Cochrane Library and other important databases up to October 2006 (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 42 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: arachis oil, biofeedback, bisacodyl, cascara, docusate, exercise, glycerine suppositories, glycerol, high-fibre diet, increasing fluids, ispaghula husk, lactitol, lactulose, macrogols (polyethylene glycols), magnesium salts, methylcellulose, paraffin, phosphate enemas, seed oils, senna, sodium citrate enemas, sterculia.
Topics: Adult; Biofeedback, Psychology; Bisacodyl; Constipation; Defecation; Humans; Polyethylene Glycols
PubMed: 19454117
DOI: No ID Found -
BMJ Clinical Evidence Apr 2010Constipation is reported in 52% of people with advanced malignancy. This figure rises to 87% in people who are terminally ill and taking opioids. Constipation may be the... (Review)
Review
INTRODUCTION
Constipation is reported in 52% of people with advanced malignancy. This figure rises to 87% in people who are terminally ill and taking opioids. Constipation may be the most common adverse effect of opioids. There is no reason to believe that people with chronic non-malignant disease who take opioids will be any less troubled by this adverse effect.
METHODS AND OUTCOMES
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of: oral laxatives, rectally applied medications, and opioid antagonists for constipation in people prescribed opioids? We searched: Medline, Embase, The Cochrane Library, and other important databases up to August 2009 (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 23 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: arachis oil enemas, bisacodyl, co-danthrusate/co-danthramer, docusate, glycerol suppositories, ispaghula husk, lactulose, liquid paraffin, macrogols plus electrolyte solutions, magnesium salts, methylcellulose, opioid antagonists, phosphate enemas, senna, sodium citrate micro-enema, and sodium picosulfate.
Topics: Analgesics, Opioid; Constipation; Dioctyl Sulfosuccinic Acid; Humans; Lactulose; Laxatives
PubMed: 21718572
DOI: No ID Found -
World Journal of Gastroenterology Mar 2014Pre-procedural cleansing of the bowel can maximize the effectiveness and efficiency of colonoscopy. Yet, efficacy of the current gold standard colonic preparation method... (Review)
Review
Pre-procedural cleansing of the bowel can maximize the effectiveness and efficiency of colonoscopy. Yet, efficacy of the current gold standard colonic preparation method - high-volume oral administration of purgative agents 12-24 h prior to the procedure - is limited by several factors, such as patient compliance (due to poor palatability and inconvenience of the dosing regimen) and risks of complications (due to drug interactions or intolerance). Attempts to resolve these limitations have included providing adjunctive agents and methods to promote the colonic cleansing ability of the principal purgative agent, with the aim of lessening unpleasant side effects (such as bloating) and reducing the large ingested volume requirement. Several promising adjunctive agents are bisacodyl, magnesium citrate, senna, simethicone, metoclopramide, and prokinetics, and each are being investigated for their potential. This review provides an up to date summary of the reported investigations into the potencies and weaknesses of the key adjuncts currently being applied in clinic as supplements to the traditional bowel preparation agents. While the comparative analysis of these adjuncts showed that no single agent or method has yet achieved the goal of completely overcoming the limitations of the current gold standard preparation method, they at least provide endoscopists with an array of alternatives to help improve the suboptimal efficacy of the main cleansing solutions when used alone. To aid in this clinical endeavor, a subjective grade was assigned to each adjunct to indicate its practical value. In addition, the systematic review of the currently available agents and methods provides insight into the features of each that may be overcome or exploited to create novel drugs and strategies that may become adopted as effective bowel cleansing adjuncts or alternatives.
Topics: Cathartics; Colonoscopy; Humans
PubMed: 24659864
DOI: 10.3748/wjg.v20.i11.2735 -
Cancer Treatment Reviews Apr 2024Cancer-related pain often requires opioid treatment with opioid-induced constipation (OIC) as its most frequent gastrointestinal side-effect. Both for prevention and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Cancer-related pain often requires opioid treatment with opioid-induced constipation (OIC) as its most frequent gastrointestinal side-effect. Both for prevention and treatment of OIC osmotic (e.g. polyethylene glycol) and stimulant (e.g. bisacodyl) laxatives are widely used. Newer drugs such as the peripherally acting µ-opioid receptor antagonists (PAMORAs) and naloxone in a fixed combination with oxycodone have become available for the management of OIC. This systematic review and meta-analysis aims to give an overview of the scientific evidence on pharmacological strategies for the prevention and treatment of OIC in cancer patients.
METHODS
A systematic search in PubMed, Embase, Web of Science and the Cochrane Library was completed from inception up to 22 October 2022. Randomized and non-randomized studies were systematically selected. Bowel function and adverse drug events were assessed.
RESULTS
Twenty trials (prevention: five RCTs and three cohort studies; treatment: ten RCTs and two comparative cohort studies) were included in the review. Regarding the prevention of OIC, three RCTs compared laxatives with other laxatives, finding no clear differences in effectivity of the laxatives used. One cohort study showed a significant benefit of magnesium oxide compared with no laxative. One RCT found a significant benefit for the PAMORA naldemedine compared with magnesium oxide. Preventive use of oxycodone/naloxone did not show a significant difference in two out of three other studies compared to oxycodone or fentanyl. A meta-analysis was not possible. Regarding the treatment of OIC, two RCTs compared laxatives, of which one RCT found that polyethylene glycol was significantly more effective than sennosides. Seven studies compared an opioid antagonist (naloxone, methylnaltrexone or naldemedine) with placebo and three studies compared different dosages of opioid antagonists. These studies with opioid antagonists were used for the meta-analysis. Oxycodone/naloxone showed a significant improvement in Bowel Function Index compared to oxycodone with laxatives (MD -13.68; 95 % CI -18.38 to -8.98; I = 58 %). Adverse drug event rates were similar amongst both groups, except for nausea in favour of oxycodone/naloxone (RR 0.51; 95 % CI 0.31-0.83; I = 0 %). Naldemedine (NAL) and methylnaltrexone (MNTX) demonstrated significantly higher response rates compared to placebo (NAL: RR 2.07, 95 % CI 1.64-2.61, I = 0 %; MNTX: RR 3.83, 95 % CI 2.81-5.22, I = 0 %). With regard to adverse events, abdominal pain was more present in treatment with methylnaltrexone and diarrhea was significantly more present in treatment with naldemedine. Different dosages of methylnaltrexone were not significantly different with regard to both efficacy and adverse drug event rates.
CONCLUSIONS
Magnesium oxide and naldemedine are most likely effective for prevention of OIC in cancer patients. Naloxone in a fixed combination with oxycodone, naldemedine and methylnaltrexone effectively treat OIC in cancer patients with acceptable adverse events. However, their effect has not been compared to standard (osmotic and stimulant) laxatives. More studies comparing standard laxatives with each other and with opioid antagonists are necessary before recommendations for clinical practice can be made.
Topics: Humans; Laxatives; Analgesics, Opioid; Narcotic Antagonists; Constipation; Oxycodone; Opioid-Induced Constipation; Magnesium Oxide; Cohort Studies; Naloxone; Polyethylene Glycols; Neoplasms; Drug-Related Side Effects and Adverse Reactions; Quaternary Ammonium Compounds; Naltrexone
PubMed: 38452708
DOI: 10.1016/j.ctrv.2024.102704 -
Canadian Journal of Gastroenterology &... Nov 2014Constipation is an uncomfortable and common condition that affects many, irrespective of age. Since 1500 BC and before, health care practitioners have provided... (Review)
Review
BACKGROUND
Constipation is an uncomfortable and common condition that affects many, irrespective of age. Since 1500 BC and before, health care practitioners have provided treatments and prevention strategies to patients for chronic constipation despite the significant variation in both medical and personal perceptions of the condition.
OBJECTIVE
To review relevant research evidence from clinical studies investigating the efficacy and safety of commercially available pharmacological laxatives in Canada, with emphasis on studies adopting the Rome criteria for defining functional constipation.
SEARCH METHODS
PubMed, Medline, Embase and Evidence-Based Medicine Reviews databases were searched for blinded or randomized clinical trials and meta-analyses assessing the efficacy of nonstimulant and stimulant laxatives for the treatment of functional constipation.
RESULTS
A total of 19 clinical studies and four meta-analyses were retrieved and abstracted regarding study design, participants, interventions and outcomes. The majority of studies focused on polyethylene glycol compared with placebo. Both nonstimulant and stimulant laxatives provided better relief of constipation symptoms than placebo according to both objective and subjective measures. Only one study compared the efficacy of a nonstimulant versus a stimulant laxative, while only two reported changes in quality of life. All studies reported minor side effects due to laxative use, regardless of treatment duration, which ranged from one week to one year. Laxatives were well tolerated by both adults and children.
Topics: Bisacodyl; Canada; Citrates; Constipation; Dioctyl Sulfosuccinic Acid; Humans; Lactulose; Laxatives; Magnesium Oxide; Organometallic Compounds; Paraffin; Picolines; Polyethylene Glycols; Psyllium; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 25390617
DOI: 10.1155/2014/631740