Abstract
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.
Key Points
People with chronic idiopathic constipation can be divided into two main categories: those with difficulty defecating (but with normal bowel motion frequency) and those with a transit abnormality (which can present as infrequent defecation).
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 being written in England in 2001.
Increasing fibre intake and exercise may improve the symptoms and prevalence of constipation.
We haven't found sufficient evidence examining the effects of other non-drug interventions, such as increasing fluid intake or performing biofeedback, although biofeedback may be useful for constipation caused by pelvic floor dyssynergia.
Despite this lack of firm evidence, a number of poorer-quality studies have implicated these lifestyle interventions as potentially beneficial.
Macrogols (polyethylene glycols) improve symptoms of constipation without any serious adverse effects.
Lactitol and lactulose may be equally effective in improving the frequency of bowel movements.
We found no RCTs on the effects of magnesium salts, or phosphate or sodium citrate enemas .
The bulk-forming laxative ispaghula husk (psyllium) seems more effective than lactulose at improving overall symptoms of constipation.
Prucalopride and lubiprostone seem to be more effective than placebo at improving frequency of bowel movements and spontaneous complete bowel movements in people with chronic constipation.
Although the efficacy of lubiprostone has been shown in RCTs, we are unsure about its role because of relatively frequent adverse events.
We don't know whether other bulk-forming laxatives, such as methylcellulose or sterculia, are effective for improving symptoms of constipation.
We don't know the effectiveness of stimulant laxatives, such as bisacodyl, cascara, docusate, glycerol/glycerine suppositories, or senna.
Although generally considered beneficial, we did not find any evidence examining the use of the faecal softeners paraffin and seed oils/arachis oil for treating constipation.
About this condition
Definition
Bowel habits and perception of bowel habits vary widely within and among populations, making constipation difficult to define. People with constipation can be divided into two main categories: those with difficulty defecating (but normal bowel motion frequency) and those with a transit abnormality (which can present as infrequent defecation). The Rome III criteria is a standardised tool that diagnoses chronic constipation on the basis of two or more of the following symptoms for at least 12 weeks in the preceding 6 months: straining at defecation on at least one quarter of occasions, stools that are lumpy/hard on at least one quarter of occasions, sensation of incomplete evacuation on at least one quarter of occasions, and three or fewer bowel movements a week. In practice, however, diagnostic criteria are less rigid and are in part dependent on perception of normal bowel habit. Typically, chronic constipation is diagnosed when a person has bowel actions twice a week or less for two consecutive weeks, especially in the presence of features such as straining at stool, abdominal discomfort, and sensation of incomplete evacuation. Population: For the purposes of this review we included all RCTs stating that all participants had chronic constipation, whether or not this diagnosis was made according to strict Rome III criteria. Where the definitions of constipation in the RCTs differ markedly from those presented here, we have made this difference explicit. In this review, we deal with chronic constipation not caused by a specific underlying disease (sometimes known as idiopathic constipation) in adults aged over 18 years, although we have included adults with pelvic floor dyssynergia. We excluded studies in pregnant women and in people with constipation associated with underlying specific organic diseases such as dehydration, autonomic neuropathy, spinal cord injury, bowel obstruction, irritable bowel syndrome, or paralytic ileus. We excluded people with Parkinson's disease and dementia, people who were post operative, or who were terminally ill. Opioid-induced constipation was also excluded. Diagnosis: The diagnosis of constipation is initially based on history (see above). Specific tests available for further investigation include thyroid function tests, calcium concentration, barium enema or colonoscopy, defecation proctogram, anorectal manometry, and colon transit time studies.
Incidence/ Prevalence
Twelve million general practitioner prescriptions were written for laxatives in England in 2001. Prevalence data are limited by small samples and problems with definition. One UK survey of 731 women found that 8.2% had constipation meeting Rome II criteria, and 8.5% defined themselves as being constipated. A larger survey (1892 adults) found that 39% of men and 52% of women reported straining at stool on more than one quarter of occasions. Prevalence rises in older people. Several surveys from around the world suggest that, in a community setting, prevalence among older people is about 20%.
Aetiology/ Risk factors
One systematic review suggested that factors associated with an increased risk of constipation included low-fibre diet, low fluid intake, reduced mobility, consumption of drugs such as opioids and anticholinergic antidepressants, and Parkinson's disease.
Prognosis
Untreated constipation can lead to faecal impaction (with resulting faecal incontinence), particularly in older and confused people. Constipation has been suggested as a risk factor for haemorrhoids and diverticular disease; however, evidence of causality is lacking.
Aims of intervention
To relieve symptoms of constipation, to restore normal bowel habit, and to improve quality of life, with minimal adverse effects.
Outcomes
Frequency of bowel movements, straining at defecation, hard/lumpy stools, sensation of incomplete evacuation/tenesmus); use of laxatives; cure of constipation (based on Rome III criteria or self or practitioner's report); adverse effects.
Methods
Clinical Evidence search and appraisal October 2009. The following databases were used to identify studies for this review: Medline 1966 to October 2009, Embase 1980 to October 2009, and The Cochrane Database of Systematic Reviews and Cochrane Central Register of Controlled Clinical Trials 2009, Issue 3. Additional searches were carried out using these websites: NHS Centre for Reviews and Dissemination (CRD) — for Database of Abstracts of Reviews of Effects (DARE) and Health Technology Assessment (HTA), Turning Research into Practice (TRIP), and National Institute for Health and Clinical Excellence (NICE). Abstracts of the studies retrieved from the initial search were assessed by an information specialist. Selected studies were then sent to the authors for additional assessment, using pre-determined criteria to identify relevant studies. Study design criteria for inclusion in this review were: published systematic reviews and RCTs in any language, and containing more than 20 individuals. There was no minimum length of follow-up required to include studies. We included all studies described as "open", "open label", or not blinded as well as any blinded studies. We also did a search for cohort studies on specific harms of named interventions. For lifestyle interventions, we also included observational studies. In addition, we use a regular surveillance protocol to capture harms alerts from organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA), which are added to the review as required. To aid readability of the numerical data in our reviews, we round many percentages to the nearest whole number. Readers should be aware of this when relating percentages to summary statistics such as relative risks (RRs) and odds ratios (ORs). We have performed a GRADE evaluation of the quality of evidence for interventions included in this review (see table ). The categorisation of the quality of the evidence (high, moderate, low, or very low) reflects the quality of evidence available for our chosen outcomes in our defined populations of interest. These categorisations are not necessarily a reflection of the overall methodological quality of any individual study, because the Clinical Evidence population and outcome of choice may represent only a small subset of the total outcomes reported, and population included, in any individual trial. For further details of how we perform the GRADE evaluation and the scoring system we use, please see our website (www.clinicalevidence.com).
Table 1.
GRADE evaluation of interventions for constipation in adults
| Important outcomes | Frequency of bowel movement, straining during defecation, hard stool, laxative use, cure of constipation, adverse effects | ||||||||
| Number of studies (participants) | Outcome | Comparison | Type of evidence | Quality | Consistency | Directness | Effect size | GRADE | Comment |
| What are the effects of non-drug interventions in adults with idiopathic chronic constipation? | |||||||||
| 1 (59) | Frequency of bowel movement | Fibre-rich diet v lower-fibre diet | 4 | –1 | 0 | –1 | 0 | Low | Quality point deducted for sparse data. Directness point deducted for inclusion of co-intervention in statistical analysis |
| 1 (59) | Straining during defecation | Fibre-rich diet v lower-fibre diet | 4 | –1 | 0 | –1 | 0 | Low | Quality point deducted for sparse data. Directness point deducted for inclusion of co-intervention in statistical analysis |
| 1 (59) | Hard stool | Fibre-rich diet v lower-fibre diet | 4 | –1 | 0 | –1 | 0 | Low | Quality point deducted for sparse data. Directness point deducted for inclusion of co-intervention in statistical analysis |
| 1 (43) | Cure of constipation | Exercise v normal lifestyle | 4 | –2 | 0 | 0 | 0 | Low | Quality points deducted for sparse data and for not assessing statistical significance |
| 1 (43) | Frequency of bowel movement | Exercise v normal lifestyle | 4 | –3 | 0 | 0 | 0 | Very low | Quality points deducted for sparse data, incomplete reporting of results (absolute numbers not reported), and for not assessing statistical significance |
| 1 (43) | Straining during defecation | Exercise v normal lifestyle | 4 | –3 | 0 | 0 | 0 | Very low | Quality points deducted for sparse data, incomplete reporting of results (absolute numbers not reported), and for not assessing statistical significance |
| 1 (43) | Hard stool | Exercise v normal lifestyle | 4 | –3 | 0 | 0 | 0 | Very low | Quality points deducted for sparse data, incomplete reporting of results (absolute numbers not reported), and for not assessing statistical significance |
| 1 (117) | Frequency of bowel movement | Increased fluid intake plus high-fibre diet v high-fibre diet alone | 4 | –1 | 0 | 0 | 0 | Moderate | Quality point deducted for sparse data |
| 1 (117) | Laxative use | Increased fluid intake plus high-fibre diet v high-fibre diet alone | 4 | –1 | 0 | 0 | 0 | Moderate | Quality point deducted for sparse data |
| 1 (60) | Straining during defecation | Biofeedback plus balloon defecation training v balloon defecation training alone | 4 | –3 | 0 | 0 | 0 | Very low | Quality point deducted for sparse data, incomplete reporting of results (significance not assessed), and other methodological flaws |
| 1 (77) | Cure rate | Biofeedback v sham/standard treatment | 4 | –2 | 0 | 0 | 0 | Low | Quality points deducted for sparse data and for incomplete reporting (data presented graphically). |
| 1 (109) | Frequency of bowel movement | Biofeedback v macrogols | 4 | –2 | 0 | –1 | 0 | Very low | Quality points deducted for sparse data and for incomplete reporting (data presented graphically). Directness point deducted for co-intervention (advice on prevention of constipation) in only one arm |
| 1 (77) | Frequency of bowel movement | Biofeedback v sham/standard treatment | 4 | –2 | 0 | 0 | 0 | Low | Quality points deducted for sparse data and for incomplete reporting (data presented graphically) |
| 1 (109) | Straining during defecation | Biofeedback v macrogols | 4 | –1 | 0 | –1 | 0 | Low | Quality point deducted for sparse data. Directness point deducted for co-intervention (advice on prevention of constipation) in only one arm |
| 1 (77) | Straining during defecation | Biofeedback v sham/standard treatment | 4 | –2 | 0 | 0 | 0 | Low | Quality points deducted for sparse data and for incomplete reporting (data presented graphically) |
| 1 (109) | Laxative use | Biofeedback v macrogols | 4 | –1 | 0 | –1 | 0 | Low | Quality point deducted for sparse data. Directness point deducted for co-intervention (advice on prevention of constipation) in only one arm |
| 1 (77) | Laxative use | Biofeedback v sham/standard treatment | 4 | –2 | 0 | 0 | 0 | Low | Quality points deducted for sparse data and for incomplete reporting (data presented graphically) |
| What are the effects of bulk-forming laxatives in adults with idiopathic chronic constipation? | |||||||||
| 1 (201) | Frequency of bowel movement | Ispaghula husk v placebo | 4 | 0 | 0 | 0 | 0 | High | |
| 1 (196) | Straining during defecation | Ispaghula husk v placebo | 4 | –1 | 0 | 0 | 0 | Moderate | Quality point deducted for sparse data |
| 1 (124) | Frequency of bowel movement | Ispaghula husk v lactulose | 4 | –2 | 0 | 0 | 0 | Low | Quality points deducted for sparse data and incomplete reporting of results (data presented graphically and statistical data not reported) |
| 1 (124) | Straining during defecation | Ispaghula husk v lactulose | 4 | –2 | 0 | 0 | 0 | Low | Quality points deducted for sparse data and incomplete reporting of results (statistical data not reported) |
| 1 (170) | Frequency of bowel movement | Ispaghula husk v docusate | 4 | –1 | 0 | –1 | 0 | Low | Quality point deducted for sparse data. Directness point deducted for uncertainty of clinical benefit |
| 1 (170) | Straining during defecation | Ispaghula husk v docusate | 4 | –1 | 0 | 0 | 0 | Moderate | Quality point deducted for sparse data |
| What are the effects of faecal softeners in adults with idiopathic chronic constipation? | |||||||||
| We found no studies on the effects of faecal softeners | |||||||||
| What are the effects of osmotic laxatives in adults with idiopathic chronic constipation? | |||||||||
| 1 (304) | Cure rate | Macrogols v placebo | 4 | –1 | 0 | 0 | 0 | Moderate | Quality point deducted for incomplete reporting of results |
| 4 (544) | Frequency of bowel movement | Macrogols v placebo | 4 | –2 | 0 | 0 | 0 | Low | Quality point deducted for non-assessment of significance in one RCT, and incomplete reporting of results in one RCT |
| 1 (55) | Straining during defecation | Macrogols v placebo | 4 | –2 | 0 | 0 | 0 | Low | Quality point deducted for sparse data and for incomplete reporting (absolute numbers not reported) |
| 1 (304) | Laxative use | Macrogols v placebo | 4 | –1 | 0 | 0 | 0 | Moderate | Quality point deducted for incomplete reporting of results |
| 2 (183) | Frequency of bowel movement | Macrogols v ispaghula husk | 4 | –2 | 0 | –2 | 0 | Very low | Quality points deducted for sparse data and incomplete reporting of results. Directness points deducted for unclear outcomes and inclusion of a co-intervention (electrolytes) |
| 1 (120) | Hard stool | Macrogols v ispaghula husk | 4 | –1 | 0 | –2 | 0 | Very low | Quality point deducted for sparse data. Directness points deducted for unclear outcomes and inclusion of a co-intervention (electrolytes) |
| 1 (115) | Frequency of bowel movement | Macrogols v lactulose | 4 | –1 | 0 | 0 | 0 | Moderate | Quality point deducted for sparse data |
| 1 (115) | Straining during defecation | Macrogols v lactulose | 4 | –1 | 0 | –1 | 0 | Low | Quality point deducted for sparse data. Directness point deducted for unclear definition of outcome |
| 1 (24) | Frequency of bowel movement | Lactulose v placebo | 4 | –1 | 0 | –1 | 0 | Low | Quality point deducted for sparse data. Directness point deducted for using high-dose of intervention |
| 1 (30) | Hard stool | Lactulose v placebo | 4 | –2 | 0 | –1 | 0 | Very low | Quality points deducted for sparse data and for not reporting pre-crossover results. Directness point deducted for unclear definition of outcome |
| 1 (43) | Frequency of bowel movement | Lactitol v placebo | 4 | –2 | 0 | –1 | 0 | Very low | Quality points deducted for sparse data and incomplete reporting of results. Directness point deducted for including only people in nursing homes |
| 3 (181) | Frequency of bowel movement | Lactitol v lactulose | 4 | –2 | 0 | 0 | 0 | Low | Quality points deducted for sparse data and incomplete reporting of results |
| What are the effects of stimulant laxatives in adults with idiopathic chronic constipation? | |||||||||
| 1 (55) | Frequency of bowel movement | Bisacodyl v placebo | 4 | –2 | 0 | 0 | 0 | Low | Quality points deducted for sparse data and short follow-up |
| 1 (55) | Hard stool | Bisacodyl v placebo | 4 | –2 | 0 | 0 | 0 | Low | Quality points deducted for sparse data and short follow-up |
| What are the effects of prostaglandin derivatives in people with idiopathic chronic constipation? | |||||||||
| 2 (371) | Cure rate | Lubiprostone v placebo | 4 | –1 | 0 | 0 | 0 | Moderate | Quality point deducted for incomplete reporting of results |
| 2 (371) | Frequency of bowel movement | Lubiprostone v placebo | 4 | –1 | 0 | 0 | 0 | Moderate | Quality point deducted for incomplete reporting of results |
| 2 (371) | Straining during defecation | Lubiprostone v placebo | 4 | –1 | 0 | 0 | 0 | Moderate | Quality point deducted for incomplete reporting of results |
| 2 (371) | Hard stools | Lubiprostone v placebo | 4 | –1 | 0 | 0 | 0 | Moderate | Quality point deducted for incomplete reporting of results |
| 2 (371) | Laxative use | Lubiprostone v placebo | 4 | –1 | 0 | 0 | 0 | Moderate | Quality point deducted for incomplete reporting of results |
| What are the effects of 5-HTA agonists in people with idiopathic chronic constipation? | |||||||||
| 1 (53) | Cure rate | Prucalopride v placebo | 4 | –2 | 0 | 0 | 0 | Low | Quality points deducted for sparse data and incomplete reporting of results |
| 4 (2056) | Frequency of bowel movement | Prucalopride v placebo | 4 | 0 | 0 | 0 | 0 | High | |
| 1 (641) | Hard stool | Prucalopride v placebo | 4 | 0 | 0 | 0 | 0 | High | |
| 3 (1885) | Straining during defecation | Prucalopride v placebo | 4 | 0 | 0 | 0 | 0 | High | |
Type of evidence: 4 = RCT; 2 = Observational.Consistency: similarity of results across studies Directness: generalisability of population or outcomes Effect size: based on relative risk or odds ratio
Glossary
- Anismus
Paradoxical contraction of the puborectalis, anal sphincter muscles, or both, resulting in difficulty defecating.
- Biofeedback therapy
involves training the person to relax pelvic floor and anal sphincter muscles using different types of equipment, from balloons for inserting into the rectum to electrical devices to determine muscle contraction.
- High-quality evidence
Further research is very unlikely to change our confidence in the estimate of effect.
- Low-quality evidence
Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
- Moderate-quality evidence
Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
- Rome II criteria
(updated 1999) Rome criteria for constipation require two or more of the following symptoms to be present for at least 12 weeks out of the preceding 12 months: straining at defecation on at least a quarter of occasions; stools are lumpy/hard on at least a quarter of occasions; sensation of incomplete evacuation on at least a quarter of occasions; and three or fewer bowel movements a week.
- Tenesmus
A continual inclination to evacuate the bowels with a feeling of incomplete rectal emptying.
- Very low-quality evidence
Any estimate of effect is very uncertain.
Constipation in children
Disclaimer
The information contained in this publication is intended for medical professionals. Categories presented in Clinical Evidence indicate a judgement about the strength of the evidence available to our contributors prior to publication and the relevant importance of benefit and harms. We rely on our contributors to confirm the accuracy of the information presented and to adhere to describe accepted practices. Readers should be aware that professionals in the field may have different opinions. Because of this and regular advances in medical research we strongly recommend that readers' independently verify specified treatments and drugs including manufacturers' guidance. Also, the categories do not indicate whether a particular treatment is generally appropriate or whether it is suitable for a particular individual. Ultimately it is the readers' responsibility to make their own professional judgements, so to appropriately advise and treat their patients.To the fullest extent permitted by law, BMJ Publishing Group Limited and its editors are not responsible for any losses, injury or damage caused to any person or property (including under contract, by negligence, products liability or otherwise) whether they be direct or indirect, special, incidental or consequential, resulting from the application of the information in this publication.
Contributor Information
Professor of Medicine Stefan A Mueller-Lissner, Park-Klinik Weissensee Berlin, Berlin, Germany.
Professor of Medicine Arnold Wald, University of Wisconsin, Madison, WI, USA.
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