In reviewing the evidence (from randomized controlled trials [RCTs] except where observational studies provide clinically relevant evidence on associations) CKS excluded studies which:
- Compared a laxative with a placebo (although the findings of recent systematic reviews are briefly summarized).
- The reason for excluding placebo-controlled trials is that, for any individual, it is quick and easy to tell if a laxative has the desired effect, so evidence from such a trial provides little information that would guide clinical decisions.
- Compared a laxative given in a fixed dose with an alternative treatment.
- The reason for excluding these trials is that they provide little information relevant to choosing between laxatives, because in clinical practice the dose and frequency of laxative should be dynamically adjusted to the response to treatment.
- Provided information only on laxatives or treatments which are not used or not licensed in the UK (except in the case of fibre supplements, because the evidence can be extrapolated to the more general recommendation to increase dietary fibre).
- Provided information only on treatments which would be used in specialist services and not in primary care.
- Included fewer than 15 participants in comparison groups (unless there was a dramatic effect).
- The reason for excluding these trials is that the results are statistically unreliable and should be used to guide future research, not clinical practice.
CKS found:
- Dehydration, reduced levels of physical activity and low levels of dietary fibre are associated with constipation. However, the clinical impression is that increasing fluids above an adequate daily intake, increasing exercise, and advice to increase dietary fibre does not always relieve constipation. Increased fluid is needed with bulk-forming agents and osmotic laxatives to reduce adverse effects.
- Advice to increase the consumption of fibre or sources of fibre in fruit vegetables and oats can be ineffective in changing the diet (one large RCT and one small observational study). There is an association between low dietary intake of fibre and constipation (one large questionnaire study). Increasing the consumption of foods rich in fibre decreased the symptoms of constipation (one small RCT). Foods (fruits, with and without oats and oat bran) prepared for use as natural laxatives were effective in increasing the frequency of bowel movements (two small RCTs).
- Systematic reviews (which had some clinically unimportant differences in the trials that were included) found good evidence from placebo-controlled trials that macrogols (five RCTs) are effective, and weaker evidence from RCTs (mostly with suboptimal design) that ispaghula husk (three RCTs), lactulose (three RCTs), and bisacodyl (one RCT) are effective. The reviews found no placebo-controlled RCTs meeting their inclusion criteria for: magnesium salts, methyl cellulose, senna, sterculia, bisacodyl, docusate, paraffin, glycerol suppositories, phosphate enemas, sodium citrate enemas, or arachis oil enemas [American College of Gastroenterology Chronic Constipation Task Force, 2005; Frizelle and Barclay, 2007; Paré et al, 2007].
CKS found trials more recent than the systematic reviews, which provide evidence that:
- Bisacodyl and sodium picosulfate are equally well tolerated and effective in the treatment of chronic constipation (one open-label RCT).
- Lactulose was more effective than ispaghula husk in improving the frequency of bowel movements and consistency of stool (one RCT).
Experts are in agreement on the general approach to treating constipation: clear faecal loading/impaction before starting to treat chronic constipation; use a stepped approach to treatment and adjust the dose, frequency, and combination of laxatives according to individual preference and response to treatment [Locke et al, 2000; Hsieh, 2005; Ginsberg et al, 2007; Paré et al, 2007].
The evidence for the efficacy and safety of all laxatives is limited, mainly because these agents have been in use for a long time, clinical trials were far less robust at the time they were originally licensed, few new clinical trials have been done, and few trials have addressed clinically relevant questions such as what approach (e.g. a combination of bowel-friendly diet, fluids, exercise, behaviour training, bowel disimpaction, and then regular laxatives adjusted according to the response) is effective in terms of acceptability, relief of symptoms, and restoration of comfortable bowel movements without the aid of laxatives.
There are at least two ongoing trials that will address some of the limitations in the evidence base for the treatment of constipation: