Constipation

Overview 
Theory 
Diagnosis 
Management 
Follow up 
Resources 

The approach to treatment depends on whether the constipation is diagnosed as a primary or a secondary condition (e.g., drug-induced constipation, pregnancy, Parkinson's disease). Secondary causes are treated appropriately. In drug-induced constipation, the initial step is to withdraw the drug if possible. Constipation in pregnant women is managed with fibre and laxatives, with consideration of withdrawal of iron supplements.[21][22]

Initial management of primary constipation will depend on whether the presentation is acute (<3 months) or chronic (≥3 months). Initial management of chronic constipation, irrespective of the cause, focuses on diet and lifestyle changes, ensuring adequate fibre intake and dietary modification. If the condition persists, laxatives are used and potential underlying causes are considered.[Figure caption and citation for the preceding image starts]: Treatment algorithm for constipation (non-opioid induced). PEG: polyethylene glycol (macrogols)Created by BMJ Knowledge Centre from material supplied by Satish Rao, MD and Ashok Attaluri, MD [Citation ends]. com.bmj.content.model.Caption@278593e0

Initial management of acute primary constipation (symptoms <3 months)

When constipation presents acutely, it is important to consider possible secondary causes, including colorectal cancer. Further investigations may be performed to exclude secondary causes. Enemas, suppositories, large volume polyethylene glycol (PEG) solution (also known as macrogols), stimulant laxatives, or disimpaction with sedation may be required if there is faecal impaction. The type of enemas or drugs, and the need for sedation/anaesthesia, are all variables and depend on the clinical setting and individual patient characteristics (e.g., patient age, anxiety, first or recurrent episode). Enemas are contraindicated in patients with neutropenia, thrombocytopenia, intestinal obstruction, recent colorectal or gynecological surgery, inflammatory colitis, toxic megacolon, abdominal infection or inflammation, recent anal or rectal trauma, undiagnosed abdominal pain, or recent pelvic radiotherapy.[51][52]

If faecal impaction is absent and secondary causes are excluded, the treatment is the same as for patients with chronic constipation. This includes diet and lifestyle advice, plus laxatives or prunes and/or stool softeners (see section on chronic primary constipation below for further details).

Initial management of chronic primary constipation (symptoms ≥3 months)

Initial steps in the management of chronic primary constipation are:

Patient education
Lifestyle modifications
Correct body posture[53]
High-fibre diet
Increased fluid
Regular exercise
Bulk laxatives, prunes, or fruit-based laxatives (see section on laxatives below for further details).

Dietary and lifestyle changes may be helpful, and evidence suggests they may be most effective when combined.[18] Studies have found conflicting results suggesting that exercise or increased fluid intake alone may not be effective in patients with constipation, but one uncontrolled study combining education on dietary patterns, fluid intake, physical activity, and use of laxatives reported significant improvement in constipation and quality of life.[18]

Patients are advised to increase their daily dietary fibre. A diet deficient in fibre may lead to constipation, while a high-fibre diet increases stool weight and accelerates colonic transit time.[32][33] The American Gastroenterological Association-American College of Gastroenterology (AGA-ACG) suggests the use of fibre supplements for the management of chronic idiopathic constipation.[54] In people with a low calorie intake, an increased daily calorie intake is also advised. It has been shown that inadequate calorie intake can cause constipation.[35]

Patients should also be advised on adequate fluid intake, encouraged to get regular non-strenuous exercise, and advised to dedicate time for bowel movements and to avoid postponing bowel movements when an urge for defecation is felt.[34]

Laxatives for primary constipation

Laxatives are the mainstay of pharmacological treatment and are considered long-term therapy in patients who do not respond to lifestyle or dietary modification. The patient should try each class of drug for a minimum of 6 weeks, and then return for a review to evaluate the response to therapy. If there is no satisfactory clinical response, or if there are troublesome adverse effects, the patient should be switched to another class of drugs.

Dyssynergia should be considered if laxatives are ineffective after approximately 6-8 weeks.[9]

[Figure caption and citation for the preceding image starts]: Summary of laxatives for chronic constipationCreated by BMJ Knowledge Centre [Citation ends]. com.bmj.content.model.Caption@1cb68cb2

First-line options

Bulk laxatives (fibre supplements), prunes, or fruit-based laxatives are the preferred first-line therapy. In patients who complain of hard stool and straining at stool, stool softeners may be used.

In patients who have occasional loose stool in between episodes of constipation, a bulk laxative may be preferred. In one meta-analysis of 16 randomised controlled trials (RCTs), fibre supplements were shown to be effective at improving chronic constipation (RR 1.48, 95% CI 1.17 to 1.88), with significant effects from ispaghula and pectin supplements at higher doses (>10 g/day) for longer treatment durations (≥4 weeks).[32] Bulk laxatives do not get absorbed systemically and are considered safe for administration during pregnancy.[22] Bulk laxatives can produce excessive gas, leading to flatulence and bloating, which may deter patients from continuing treatment.[55]

Prunes (dried plums) are a natural alternative to laxatives and have been shown in a blinded randomised controlled study to be as effective as ispaghula (ispaghula husk) in improving symptoms of constipation.[56] Kiwifruit may also be effective and associated with less patient dissatisfaction than prunes or ispaghula, but one systematic review reported evidence is low to very low certainty.[57][58] Fruit-based laxatives include preparations (e.g., powder, paste) of kiwi, mango, prunes, or fig.[59] Studies suggest they are well tolerated with few or no mild gastrointestinal adverse effects reported.

Stool softeners such as docusate (a surfactant thought to hydrate and soften stool by lowering the surface tension at stool’s oil-water interface) are one of the most commonly used non-prescription drugs for treatment of constipation.[59] However, clinical data have remained inconsistent and there have been no new efficacy studies since 2004. In one study, docusate was found to be no more effective than placebo and significantly inferior to ispaghula.[60] Adverse effects of stool softeners include a bitter taste in the mouth, nausea, diarrhoea, and cramping.

Second-line options

If there is no clinical response (defined as patient satisfaction with bowel habits and associated symptoms) after at least 6 weeks of therapy, and no suspicion of dyssynergia, osmotic laxatives such as lactulose, PEG (macrogols), or magnesium-containing laxatives are considered.[54][61][62] Often a single class of laxative is used as much as possible. One meta-analysis has shown that PEG (macrogols) is better than lactulose in improving outcome measures of stool frequency per week, form of stool, relief of abdominal pain, and the need for additional products.[61] Based on the evidence, AGA-ACG made a strong recommendation for the use of PEG (either following or in combination with fibre supplements) in the management of chronic idiopathic constipation, and weak recommendations for the use of lactulose or magnesium oxide.[54] Lactulose and PEG are considered safe for administration during pregnancy.[22] The main adverse effects of osmotic laxatives include bloating, diarrhoea, epigastric pain, flatulence, nausea, vomiting, and, rarely, hypernatraemia and hypokalaemia. Common adverse effects of magnesium-containing laxatives include nausea, diarrhoea, and hypermagnesaemia.

Stimulant laxatives, such as bisacodyl and senna, are another option at this stage. They may also be used as rescue laxatives in patients using another class of laxatives (to be used if the patient does not have a bowel movement for 3 days).[63] Systematic reviews have found that while stimulant laxatives are effective, diarrhoea and abdominal pain are common, which may impact their tolerability.[59][64] AGA-ACG recommend bisacodyl for daily use up to 4 weeks or as a rescue therapy. A gradual increase in dose is suggested to improve tolerability. They also suggest senna for the management of chronic idiopathic constipation.[54] Stimulant laxatives should be avoided during pregnancy as safety data are conflicting.[21]

One systematic review evaluating RCTs of non-prescription constipation drugs concluded that PEG and senna were supported by good evidence.[59] Fibre supplements (ispaghula); fruit-based laxatives (preparations of kiwi, mango, prunes, fig); magnesium salts; stimulants (bisacodyl); and yogurt with galacto-oligosaccharides/prunes/linseed oil were recommended with moderate evidence. There was insufficient evidence for docusate, inulin, fructose-oligosaccharides, and polydextrose.[59]

Third-line options

If symptoms persist after at least 6 weeks of traditional laxatives and there is no suspicion of dyssynergia, newer prescription agents may be considered. Options include lubiprostone, linaclotide, plecanatide, or prucalopride. These drugs are usually used as monotherapy and not in combination with other laxatives. AGA-ACG recommend linaclotide, plecanatide, or prucalopride and suggest lubiprostone for patients with chronic idiopathic constipation that does not respond to non-prescription agents.[54] They are not recommended for pregnant patients as there is a lack of safety data for use in pregnancy.

Lubiprostone (a chloride channel activator) has been shown to be more effective than placebo in increasing the number of spontaneous bowel movements, decreasing straining, improving stool consistency, and relieving symptoms of chronic constipation.[65][66][67][68] The most common adverse events include nausea (31%), headache (13%), diarrhoea (13%), abdominal pain (7%), and distention (7%). Lubiprostone has been withdrawn from the UK market for commercial reasons.

Linaclotide and plecanatide are guanylate cyclase-C agonists. This class of drugs has been shown to be more effective than placebo in clinical trials, where it has demonstrated rapid and sustained improvements of bowel habits, bowel and abdominal symptoms and quality of life in patients with chronic constipation.[69][70][71] Linaclotide has been shown to accelerate gut transit in healthy people and in female patients with irritable bowel syndrome-constipation.[72][73] Plecanatide has similarly demonstrated to increase intracellular cyclic guanosine monophosphate (cGMP) and promote luminal secretion through the CFTR receptor to facilitate bowel movements.[71] Both linaclotide and plecanatide appear to have few adverse effects.

Prucalopride is a 5-HT4 receptor agonist with prokinetic properties. Prucalopride was the most effective laxative at 12 weeks according to one meta-analysis.[64] Headache, nausea, abdominal pain, and diarrhoea were reported by over 10% of the 4000 patients in the three phase 3 trials.[74][75][76] No clinically relevant cardiac adverse effects were reported. In one meta-analysis of 14 RCTs (total of 4328 patients), a lower daily dose obtained the maximum number of spontaneous weekly bowel movements, compared with higher doses, and higher doses were associated with more treatment-emergent adverse events.[77]

In the US, the FDA has approved a vibrating capsule for treatment of chronic constipation in adults who have not experienced symptom improvement from laxatives after at least 1 month. The vibrating capsule is a non-pharmacological device that mechanically induces colonic contractions.[78] In a double-blind phase 3 trial of patients with chronic constipation, a significantly higher proportion of patients who received the vibrating capsule experienced ≥1 complete spontaneous bowel movements per week, compared with those who received the sham placebo capsule (39.3% versus 22.1%).[79] Studies also reported improvements in quality of life, and mild gastrointestinal adverse effects.[79][80] If there has been no bowel movement within ≥3 consecutive days of using the vibrating capsule, consider adjunctive laxative therapy.

Enemas, suppositories, and digital maneuvers are not normally recommended for the management of chronic constipation. However despite lack of robust evidence, they are commonly used. Suppositories are not associated with any obvious risk, but enemas should be avoided in patients with fluid or electrolyte imbalance.[18]

Opioid-induced constipation

Opioid use should be reviewed as appropriate. Other underlying causes or factors that may contribute to constipation should also be considered and excluded.[81]

Traditional laxatives are recommended as first-line therapy for opioid-induced constipation. Osmotic or stimulant laxatives are preferred.[52][81] If response to a single agent is inadequate, some guidelines recommend combining an osmotic and stimulant laxative before escalating therapy.[52][81]

Docusate is not typically recommended due to lack of evidence.[52] Fibre (including bulk laxatives like ispaghula) may be helpful in patients with a fibre-deficient diet, but it is typically not recommended for treatment of opioid-induced constipation because it does not affect colonic motility.[51][81]

Peripherally acting mu-opioid receptor antagonists such as naldemedine, naloxegol, and methylnaltrexone are recommended for laxative-refractory opioid-induced constipation.[18][81] They can be used as monotherapy, but are often used in combination with an osmotic or stimulant laxative.[82] Data to support naldemedine come from one phase 2 and three phase 3 trials.[83][84][85] The efficacy of naloxegol was shown in one phase 2 trial and two phase 3 RCTs.[86][87][88]

The quality of evidence supporting methylnaltrexone is not as robust.[81] Out of five RCTs, only three examined an outcome of ≥3 spontaneous bowel movements per week, and most studies were in patients with cancer. However, the subcutaneous formulation of methylnaltrexone is an advantage for patients who cannot tolerate oral drugs.[81] The most common adverse effects of methylnaltrexone are abdominal cramping and flatulence. Concerns have been raised about severe abdominal pain and bowel perforation in patients with advanced cancer who were receiving methylnaltrexone for opioid-induced constipation. These concerns led the FDA to issue a warning for physicians in the US to use caution in administering methylnaltrexone to patients with known or suspected lesions in the intestinal wall, and to discontinue treatment with methylnaltrexone immediately if gastrointestinal symptoms worsen.[89] Regardless, a pooled analysis showed reduced all-cause mortality in cancer and non-cancer patients with opioid-induced constipation who took methylnaltrexone compared to placebo.[90]

One Cochrane review on peripherally acting mu-opioid receptor antagonists for opioid-induced bowel dysfunction concluded that moderate-certainty evidence supports the efficacy of naldemedine for people with cancer and subcutaneous methylnaltrexone for people receiving palliative care.[91]

Lubiprostone is also FDA approved for treatment of opioid-induced constipation in adults with non-cancer pain, and phase 3 trials found lubiprostone was more effective than placebo for opioid-induced constipation.[92] However, in practice, peripherally acting mu-opioid receptor antagonists and laxatives (e.g., PEG or magnesium compounds) are preferred due to the increased cost of lubiprostone. Other prokinetics and secretagogues (e.g., linaclotide, plecanatide, prucalopride) are not FDA approved for opioid-induced constipation.

Patients with opioid-induced constipation should also be advised on appropriate dietary and lifestyle modifications, adjusted according to the clinical setting and underlying conditions.[52][81]

There is a lack of evidence to support the use of enemas and suppositories for treatment of opioid-induced constipation, and their use is limited by inconvenience and safety concerns.[51][81] However, evacuation measures including enemas, suppositories, large volume PEG solution, stimulant laxatives, or disimpaction with sedation may be required if there is faecal impaction.[51][52][81] Enemas are contraindicated in patients with neutropenia, thrombocytopenia, intestinal obstruction, recent colorectal or gynecological surgery, inflammatory colitis, toxic megacolon, abdominal infection or inflammation, recent anal or rectal trauma, undiagnosed abdominal pain, or recent pelvic radiotherapy.[51][52]

Suspected dyssynergia

Patients with suspected dyssynergia would have already been treated in the same way as patients with chronic primary constipation, with education, lifestyle modifications, high-fibre diet, bulk laxatives, increased fluid, and exercise. They may have also been treated with osmotic or stimulant laxatives and/or stool softeners.

When these are ineffective, the possibility of dyssynergia should be considered.[9] Associated symptoms include the sensation of anal blockage, straining, and the use of digital manoeuvres to assist defecation. The diagnosis is confirmed with physiological testing. See Diagnosis approach.

Biofeedback (bowel retraining) has been found to be effective in treating dyssynergia.[93][94][95][96] Biofeedback techniques used to improve coordination of abdominal and anorectal muscles include:

Diaphragmatic muscle training with simulated defecation
Manometric guided pelvic floor retraining
Simulated defecation training.

Three RCTs have compared biofeedback therapy with either sham feedback or pharmacological therapy or placebo; all three trials found biofeedback therapy was more effective.[93][95][96]

Two RCTs reported sustained (1 year) improvement of symptoms and colorectal function, confirming the long-term efficacy of biofeedback therapy.[94][96] One study compared home biofeedback therapy to standard 6-session office-based biofeedback therapy over 3 months and reported that approximately 70% of patients in both groups met primary outcomes (i.e., normalisation of dyssynergia and improvement in the number of complete spontaneous bowel movements per week).[97]

Sixty per cent of patients with dyssynergic defecation have impaired rectal sensation, and rectal sensory conditioning provides additional therapeutic benefit.[94][98] One RCT found that barostat-assisted sensory training was superior to syringe-assisted sensory training.[99]

Patients with confirmed dyssynergia are gradually weaned off laxatives. Lifestyle and dietary changes are continued, including adequate daily fluids and increased dietary fibre.

Persistent chronic constipation despite medical therapy and lifestyle measures

Patients with persistent symptoms (lasting several months to years) that are unresponsive to medical treatment can be referred to a specialised centre for consideration of surgery, which could include colectomy and caecostomy. Such patients undergo evaluation of upper gut and small bowel motility, along with a detailed assessment of colonic motility with colonic manometry. Surgery is reserved for refractory patients with severe colonic neuropathy and relatively preserved gastric and small bowel motility. All other patients continued on medical management.

If patients have failed all therapies and have evidence for motility dysfunction not limited to the colon (in other words, if they have gastric or small bowel dysmotility), surgery is unlikely to be of benefit. Further management involves a multi-disciplinary approach, including addressing nutrition, behavioural therapy, biofeedback, psychotherapy, and cyclical laxatives. The evidence for this type of therapy is mostly anecdotal.

Caecostomy is generally preferred in institutionalised patients, and in patients with neurological lesions, in whom there seems to be a high success rate, with satisfactory results ranging from 40% to 78%.[100] Several colectomy techniques have been advocated for the treatment of chronic constipation, including segmental colectomy, ileorectal anastomosis, ileosigmoid anastomosis, caecorectal anastomosis, ileoanal anastomosis with proctocolectomy, and pouch formation or ileostomy.[101] Surgery has also been shown to be associated with a higher degree of patient satisfaction.[102] Most of these surgeries can be carried out laparoscopically.

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