Practice Therapeutics

Laxatives for chronic constipation in adults

BMJ 2012; 345 doi: http://dx.doi.org/10.1136/bmj.e6168 (Published 01 October 2012) Cite this as: BMJ 2012;345:e6168
  1. Alexander C Ford, senior lecturer, honorary consultant gastroenterologist12,
  2. Nicholas J Talley, professor of medicine3
  1. 1Leeds Gastroenterology Institute, St James’s University Hospital, Leeds LS9 7TF, UK
  2. 2Leeds Institute of Molecular Medicine, Leeds University, Leeds LS2 9JT
  3. 3Faculty of Health, University of Newcastle, Callaghan, NSW2308, Australia
  1. Correspondence to: A C Ford alexf12399{at}yahoo.com

A 25 year old woman attends her general practitioner with a six month history of constipation. Despite having increased her daily intake of fibre and water, she is still only passing two stools a week. Her general practitioner excludes red flag features (box) and finds no abnormality on examination, apart from a loaded rectum. He suggests she try using laxatives to increase her stool frequency, but she is reluctant as she has heard they are not very effective and can have adverse effects.

Red flag features in chronic constipation12

  • Recent onset of constipation in older age (> 50 years)

  • Obstructive symptoms

  • Rectal bleeding

  • Weight loss

  • Family history of colon cancer

  • Iron deficiency anaemia

  • Haem positive stool

What are laxatives?

Laxatives are foods or drugs that, when ingested, act directly on the gut (or gut contents) to increase stool frequency or ease stool passage. They differ from motility agents such as prucalopride, which exert a promotility effect after systemic absorption. Laxatives are used to treat chronic constipation, usually defined as the presence of difficult or infrequent passage of stool, often accompanied by straining or a sensation of incomplete evacuation, with symptoms present for more than three months.

Chronic constipation is common in the general population. A recent meta-analysis of population based observational studies reported a pooled prevalence of 14% worldwide, with a significantly higher prevalence in women and people of lower socioeconomic status.3 However, symptoms often fluctuate, and recent community data suggest that persistent symptoms over 10 to 20 years affect only 3% of the population.4 Population based studies also show that constipation affects quality of life, is associated with several comorbidities (including haemorrhoids and anal fissure),5 and may be associated with a modest reduction in survival.6

Laxatives may act by several mechanisms, including bulking the stool volume, softening the stool consistency, increasing the stool volume via an osmotic effect, or stimulating the intestinal mucosa or myenteric plexus to increase intestinal motility and aid peristalsis. The table gives examples of different types of laxative.

Summary of mechanism of action, dose, evidence for efficacy, and safety of individual laxatives

View this table:

How well do laxatives work?

Evidence based guidelines for management of chronic constipation do not make any firm recommendations to support the use of laxatives in the condition.1 7 8 Part of the explanation for this may be that until very recently there had been no definitive quantitative summary of all the available evidence for their efficacy. The main aim of treatment of chronic constipation is symptomatic relief. Our literature search identified no trials of stool softeners.

Bulk laxatives

There is remarkably little evidence from randomised controlled trials that bulk laxatives, in the form of either soluble or insoluble fibre, improve the symptoms of chronic constipation. A systematic review that examined the use of fibre for chronic constipation identified only six randomised controlled trials,9 four of which used soluble fibre, and two insoluble fibre. Only one trial was conducted in primary care. A formal meta-analysis was not done owing to concerns about the quality of the methods used in the identified studies. In each of the six trials (which used different endpoints) soluble fibre, when compared with placebo, led to significant improvements in overall symptoms, straining, pain on defecation, stool consistency, an increase in the mean number of stools per week, and a reduction in the number of days between stools. Whether these differences were of clinical significance is debatable. Evidence for any benefit of insoluble fibre was conflicting.

Osmotic laxatives

Six randomised placebo controlled trials of osmotic laxatives in chronic constipation were included in a recent meta-analysis.10 None were conducted entirely or partly in primary care, meaning that the findings may not be generalisable to patients consulting general practitioners. In addition, most trials recruited predominantly female patients.

Five randomised controlled trials (in 676 participants) reported dichotomous data for the efficacy of osmotic laxatives. Four of these trials used polyethylene glycol at a dose of 17 g once or twice daily for between two weeks and six months, and the fifth trial used 15 mL of lactulose once daily for three weeks. Overall, osmotic laxatives were superior to placebo, with a relative risk of symptoms failing to respond of 0.50 (95% confidence interval 0.36 to 0.63) (fig 1) and a number needed to treat of 3. Continuous data were reported by four studies (534 participants) using polyethylene glycol for between eight days and six months. The mean number of stools per week was significantly higher with osmotic laxatives than with placebo (weighted mean difference in the number of stools per week 2.51; 1.30 to 3.71) (fig 2).

We identified a Cochrane review comparing lactulose with polyethylene glycol in chronic constipation, but as this did not report data for adults and children separately, we excluded it from this review.11

Figure1

Fig 1 Effect of laxatives versus placebo in chronic constipation, in terms of number of participants with persistent symptoms10

Figure2

Fig 2 Weighted mean difference in number of stools per week during treatment with laxatives versus treatment with placebo in chronic constipation10

Stimulant laxatives

The same meta-analysis identified only two randomised controlled trials of stimulant laxatives, but these recruited 735 patients.10 Both trials were conducted partly in primary care, and most patients enrolled were female. One trial used bisacodyl 10 mg once daily for four weeks, and the other sodium picosulfate 10 mg once daily for four weeks. These two laxatives are converted to the same active metabolite. The risk ratio for failure to respond to treatment was reduced with stimulant laxatives (0.54; 0.42 to 0.69) (fig 1), and the number needed to treat was 3. Both trials reported a significant increase in the mean number of stools per week compared with placebo (weighted mean difference 2.50; 0.93 to 4.07) (fig 2).

How safe are laxatives?

Bulk laxatives

In the systematic review cited above that examined the use of fibre for chronic constipation,9 only one randomised controlled trial reported the number of participants in each treatment arm who dropped out owing to adverse events (one of 104 participants randomised to psyllium and two of 97 receiving placebo). Another trial in the review reported on individual adverse events, with 18% of the participants who took psyllium experiencing abdominal pain compared with none of the placebo participants, although no differences in bloating or cramping were reported. Finally, one other trial in the review reported significantly higher combined symptom scores for side effects such as abdominal pain, flatulence, borborygmi, and bloating among the participants eating rye bread compared with those eating low fibre toast.

Osmotic and stimulant laxatives

Four trials identified by the meta-analysis cited above reported individual adverse events.10 No significant differences were detected in rates of abdominal pain, reported in all four trials containing 853 patients, or headache, reported in three randomised controlled trials containing 486 patients. Diarrhoea occurred more frequently in the two trials of stimulant laxatives (risk ratio 13.75; 2.82 to 67.14, number needed to harm 3). Despite concerns that osmotic and stimulant laxatives may cause fluid or electrolyte disturbances, and despite recommendations that stimulant laxatives be avoided in renal impairment, no evidence from the clinical trial literature supported these warnings. There is also no convincing evidence in humans that stimulant laxatives damage the myenteric plexus, which is often cited as a hypothetical concern, although in practice the development of tolerance and increasing dose requirements have been noted.

What are the precautions?

All laxatives are contraindicated in intestinal obstruction. Avoid bulk laxatives, including psyllium, if faecal impaction is suspected, and advise patients taking these to maintain an adequate fluid intake. Lactulose should be used with caution in lactose intolerant patients (who may develop diarrhoea, as lactulose contains lactose) and is contraindicated in galactosaemia. Discontinue polyethylene glycol if symptoms suggesting fluid or electrolyte disturbance develop. In pregnancy, bulk laxatives should be used preferentially, and when these fail osmotic laxatives can be used.

How cost effective are laxatives?

Few data are available on the cost effectiveness of laxatives. A recent study used a decision analysis model to compare the cost effectiveness of polyethylene glycol with lactulose in primary care.12 The authors reported that polyethylene glycol led to higher rates of treatment success at six months (68% v 60%), at a total cost to the National Health Service of £420 (€524; $677) for six months’ treatment for an individual, compared with £419 for lactulose. The authors estimated that the cost per quality adjusted life year gained was £250 and therefore deemed polyethylene glycol to be cost effective. The study was funded by Norgine Pharmaceuticals, the manufacturers of one brand of polyethylene glycol (macrogol 3350).

How are laxatives taken and monitored?

Having weighed up the evidence on efficacy versus safety, we recommend starting with an osmotic laxative and titrating the dose as needed. The best current agent, based on these criteria, is polyethylene glycol (table). In routine clinical practice lactulose is often poorly tolerated owing to palatability. Some doctors prefer milk of magnesia, but its use is not evidence based. Some patients may prefer a trial of a bulking agent, and it is reasonable to recommend a soluble fibre in this situation. There is insufficient evidence that insoluble fibre, such as bran, is efficacious, and no evidence that stool softeners, including docusate, are efficacious.

If first line laxatives fail, it is important to ensure that another diagnosis has not been missed. In particular, pelvic floor dysfunction (paradoxical contraction of the pelvic floor muscles during attempts at defecation) should be considered and can be ruled out by doing a rectal examination (a “normal” finding is reassuring).13 If the rectal examination, carried out while asking the patient to “bear down,” suggests paradoxical contraction of the anal sphincter on straining or any other pelvic floor dysfunction, specialised testing (including anorectal physiology studies) is required to confirm the diagnosis, but this is worth while because treatment (biofeedback) can be highly effective.

The box “Tips for patients” outlines the various types of laxatives, how they might be used, and any side effects they may have. Bulk, osmotic, and stimulant laxatives are taken orally or, in the case of bisacodyl, orally or rectally. Routine monitoring is not needed for any of these agents. Given that most randomised controlled trials used at least four weeks of treatment, a reasonable trial of laxatives would be for at least a month. When possible, laxative doses should be reduced if symptoms allow.

How do laxatives compare with other drugs?

Several newer drugs have been approved, or are in development, for the treatment of chronic constipation. These include lubiprostone and linaclotide, which act on chloride channels and guanylate cyclase receptors in the intestinal enterocyte respectively, and prucalopride and velusetrag, which act on 5-HT4 receptors. However, no head to head trials have yet compared their efficacy or cost effectiveness with conventional laxatives, and these newer drugs are currently reserved for patients whose symptoms have not resolved with laxatives.

Tips for patients

  • Constipation is very common in the general population and affects between 1 in 5 and 1 in 10 people at any one time

  • Many people need no medication, but if constipation is causing discomfort then treatment may help to improve symptoms

  • Laxatives are drugs that treat constipation by increasing the frequency of your stools or easing the passing of your stools

  • There are four types of laxative: bulk, osmotic, and stimulant laxatives, and stool softeners

  • Bulk laxatives, including soluble fibre (such as psyllium) and insoluble fibre (such as bran), work by increasing the volume of stools. Soluble fibre is preferable, but bulk laxatives generally are not very effective for treating constipation. Side effects may include abdominal pain and bloating

  • Osmotic laxatives, including lactulose and polyethylene glycol, also increase stool volume by increasing water content in the large bowel. They are effective for treating constipation, and side effects are generally well tolerated, although people often find the taste of lactulose unacceptable. As they increase water content in the large bowel, symptoms of dehydration (such as lightheadedness, headache, or dark urine) may develop. If this happens, consult your doctor

  • Stimulant laxatives, including bisacodyl and sodium picosulfate, act on the large bowel to help the stool pass through it. They are effective for treating constipation but often cause diarrhoea

  • Stool softeners, such as docusate, have not been shown in trials to be effective in treating constipation

Notes

Cite this as: BMJ 2012;345:e6168

Footnotes

  • This is one of a series of occasional articles on therapeutics for common or serious conditions, covering new drugs and old drugs with important new indications or concerns. The series advisers are Robin Ferner, honorary professor of clinical pharmacology, University of Birmingham and Birmingham City Hospital, and Albert Ferro, professor of cardiovascular clinical pharmacology, King’s College London. To suggest a topic for this series, please email us at practice@bmj.com.

  • Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare: no support from any organisation for the submitted work; ACF has received speaker’s fees from Shire pharmaceuticals. NJT has been a consultant for Abbott, ARYx, Astellas Pharma, Boehringer Ingelheim, Concert Pharmaceuticals, Forest Pharmaceuticals, Ironwood Pharmaceuticals, Janssen, Johnson & Johnson, Pfizer, Procter and Gamble, Prometheus (Therapeutics and Diagnostics), Salix, Sanofi-Aventis, Theravance, Doyen Medipharm, Care Capital, Edusa Pharma, Dr Falk Parma, Meritage Pharma, NicOx, Novartis, Shire, Tranzyme, UptoDate, XenoPort, and Zeria; has received speaker’s fees from Focus Medical Services, AstraZeneca, Salix, and Ironwood; and has received funding from Janssen and Takeda in the form of investigator-initiated grants for studies examining the epidemiology of constipation in the USA and Australia. The authors declare no other relationships or activities that could appear to have influenced the submitted work.

  • Provenance and peer review: Commissioned; externally peer reviewed.

  • Patient consent not required (patient anonymised, dead, or hypothetical).

  • Contributors: Both authors conceived and designed the article and drafted the manuscript. Both have approved the final version of the manuscript to be published. ACF is guarantor.

References