Constipation: What Works, What Doesn't

David A. Johnson, MD

Disclosures

January 14, 2015

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Constipation: A Common Problem

Hello. I am Dr David Johnson, professor of medicine and chief of gastroenterology at Eastern Virginia Medical School in Norfolk, Virginia. Welcome back to another installment of GI Common Concerns – Computer Consult .

Today I want to chat about constipation. We see this all the time as gastro-enterologists, primary care providers, and extended care providers—even as gynecologists. This is a very common problem. Irritable bowel syndrome (IBS) is strongly related to chronic idiopathic constipation (CIC). The pooled global prevalence of IBS is approximately 11%, and for CIC it is approximately 14%.[1]

The problem is that we don't have good tests for these diseases. We don't have good biomarkers. We don't have good objective evidence with which to define these diseases, so typically we resort to a consensus definition of these disease states—for example, the Rome criteria for functional gastrointestinal disorders.

For IBS, the Rome criteria start with a patient who is having abdominal pain at least 3 days per month. Pain that improves with defecation is a very highly discriminating factor for IBS. Other factors are change in the frequency or consistency of the stool. Two of these three factors (improvement of pain with defecation, change in the consistency of stool, and change in the frequency of stool) with abdominal pain at least 3 days per month are required to make the diagnosis of IBS.

The diagnosis of CIC begins with a patient who is having infrequent bowel movements. The diagnostic criterion (from the Rome criteria) is fewer than three defecations per week and the "25% rule," meaning that the patient has at least two of the following symptoms 25% of the time:

  • A sense of incomplete evacuation;

  • Straining;

  • A sense of obstruction;

  • The need for some type of maneuver (digital evacuation or shifting or some type of alteration in the body position to support the pelvic floor); or

  • Lumpy or hard stools.

When we see a patient in clinic, it is hard to remember these things, but it is not hard to think through the common symptoms and register the key questions that differentiate IBS from CIC, because when we get into some of the pharmacologic drugs, the starting points for the medications are different.

I thought it would be helpful to give you some of the highlights of the evidence-based recommendations that the American College of Gastroenterology (ACG)[2] set forth for the management of IBS and CIC.

Dietary Intervention in IBS

With respect to IBS, diet is a very common recommendation. It may be helpful, and food-related sensitivities are evident in 11%-27% of patients who were evaluated in clinical trials.[3]

The two main diets are gluten restriction and the low-FODMAP [fermentable oligo-di-saccharides-mono-saccharides and polyols] diet. Those diets are very helpful in some patients but are not the "be-all, end-all."

The gluten-free diet is not necessarily indicated for patients with IBS, but it blossomed into a $10.3 billion industry in 2013 and it continues to grow. People think that the gluten-free diet is healthy. It is not necessarily healthy. Nonetheless, this gluten craze has wrapped a lot of people around a wire. Do they really need it?

Gluten is a fructan, a fermentable carbohydrate and a wheat protein, so there is a reason that removal of this fructan under the FODMAP diet might be helpful. It is not unreasonable to suggest a trial of gluten withdrawal. It probably doesn't hurt for a short period of time, but it is best done in consultation with a dietician. Vitamin and mineral deficiencies can occur when patients start to select their own diets.

The low-FODMAP diet is very difficult to follow, and the evidence overall is weak. The recommendation is not strong either, but nonetheless, it is a very easy thing to look at as far as diet modification.

The next dietary intervention is the high-fiber diet. Soluble fiber, primarily psyllium, which comes from the ispaghula husk (the type in Metamucil® and Citrucel® products), seems to be effective. In my experience, it tends to be associated with a lot of bloating and gas, but nonetheless, it is reasonable to try. The evidence and the recommendation were fairly weak, but it is a simple thing to do.

The Role of the Microbiome

The microbiome is going to transform where we are going in medicine for the next decade.

Prebiotics are substances used to accelerate the growth of microorganisms to achieve a favorable microbiome. Probiotics are live bacteria to repopulate the gut with bacteria. Or you can give an antibiotic to change the microflora. What is the evidence on all of this?

For prebiotics, there is no evidence and no strong recommendation to support their use.

Probiotics seem to be of some help, particularly for bloating and flatulence in patients with IBS. I don't see a strong recommendation, but it is certainly something to try.

The predominant antibiotic that has been studied is rifaximin, and the data suggest that it is a reasonable recommendation for diarrhea-predominant IBS. However, it is a very expensive therapy if you can't get the antibiotic covered under insurance, and it is very difficult for the patient with diarrhea-predominant IBS to get it covered.

IBS: Drugs and Other Treatments

With respect to antispasmodics, two agents with good evidence are hyoscyamine or the standard dicyclomine. The evidence on these agents was fairly good, with a number needed to treat (NNT) of 4-5. These drugs have anticholinergic side effects, with a number needed to harm (NNH) of 8-9. This is not inconsequential, but the recommendation is to try these agents in patients with a cramping component to their IBS.

Peppermint oil was very interesting. Many of us have pooh-poohed this as far as the science behind it, but there is very strong evidence for its use in IBS. Whether peppermint oil relaxes some of the muscle function or whether it attenuates the visceral hypersensitivity or changes the pain sensitivity, we don't know, but the evidence on certain formulations was fairly good. The recommendation was still weak, and you will see some intervention strategies emerging on peppermint oil for IBS in the not-too-distant future. Some significant trial data are going to be reported in the next 6-12 months that will whet your appetite on peppermint oil as an adjunctive measure in the management of IBS.

With loperamide, the antidiarrheal agent, the global symptoms of IBS are not improved. It may change diarrhea, but the recommendation was that the drug doesn't have any effect on the global symptoms.

With respect to antidepressants in IBS, there is a lot of evidence on the tricyclic antidepressants and some of the selective serotonin reuptake inhibitors (such drugs as citalopram, escitalopram, and fluoxetine). These drugs are very commonly used. The NNT for a benefit was 4, and the NNH for the negative consequences of these drugs is 9. The clinical trial data support a weak recommendation, but there is reasonable evidence that it may have some benefit in highly selected patients.

Psychological therapy is something that we don't use enough. The consensus group looked at hypnotherapy and psychological counseling. Hypnotherapy caught my eye because the NNT was 4. With a good psychologist who can work through some of the stress-management issues in IBS, it may have reasonable supporting data. This is somewhat subject-dependent and depends on the expertise available in your local area. Certain centers have a lot of expertise with this. The group from the University of North Carolina has published a lot on this strategy.[4]

The serotonin 5-HT3 antagonist alosetron had a lot of favorable trial data but also unfavorable trial data in diarrhea-predominant IBS. The NNT was 7, but the NNH was 11, and it was ultimately withdrawn from the market. Now it has been reinstated in the market, and there are ways to get this drug if you choose to use it. The data were reasonable—not a lot of evidence, but certainly enough to support its use in diarrhea-predominant IBS.

The prosecretory drug linaclotide is a guanylate peptide that bonds to the guanylate cyclase-C receptor, which regulates the bicarbonate and water secretion to modulate the effect of water migrating into the colon. The NNT was 6.. The NNH was also 6, and the side effect primarily in patients with constipation was diarrhea. It is a reasonable drug and the evidence is quite strong. It was one of the strongest recommendations that the monograph[2] supported. The second drug was lubiprostone, another secretory agent, which is involved with activation of the chloride channels and accelerating chloride and water flow into the bowel lumen. The NNT was not quite as good: 12.5, and the NNH was 10. Both lubiprostone and linaclotide were effective in constipation-predominant IBS. These had very strong evidence and strong recommendations.

There were no data to support the routine use of polyethylene glycol in IBS. It changes bowel frequency, but the global symptoms are not improved.

CIC: Therapies That Work

I will now review the evidence for the management of CIC from the ACG working group.

Fiber seems to be very effective, with strong evidence to support its use, especially the soluble fibers (psyllium) as opposed to the insoluble, bran-type fiber. Fiber is effective for increasing bowel movement frequency.

The osmotic agents (eg, polyethylene glycol formulations) were also effective in CIC through the accelerated laxative effect. The stimulant laxatives (such as bisacodyl or sodium picosulfate) seemed to be effective as well and may be something to try. The evidence was weak but nonetheless was enough to support a recommendation.

The 5-HT4 agonist prucalopride, which has been studied very extensively in Europe, is not available in the United States. Eight trials have looked at this drug. There was concern about the 5-HT4 agonists being associated with cardiac events, but none were evident in these eight trials. The NNT for improving constipation improvement was 5 in the European trials. We wait for this drug to be approved in the United States because it seems to be quite effective.

In patients with constipation-predominant IBS, the prosecretory drug linaclotide had an NNT of 6 and an NNH of 12 for diarrhea as a side effect. Lubiprostone has an NNT and NNH of 4. These drugs had fairly strong recommendations that they were very effective in CIC.

Biofeedback to improve pelvic floor dysfunction is very effective with the right patient and the right biofeedback intervention professional. The NNT is 2, so this could be effective in CIC with pelvic floor dysfunction.

There was no evidence to support probiotics in the management of CIC.

Take-Away Summary

In summary, in the management of IBS, loperamide improves diarrhea but not the global symptoms of IBS. The prosecretory drugs (linaclotide and lubiprostone) seem to be very effective in constipation-predominant IBS, with a strong level of evidence and a strong recommendation. For CIC, the strongest evidence is for polyethylene glycol in increasing the frequency of stools. Linaclotide and lubiprostone also had strong support that they improve the frequency of stools in CIC.

Hopefully this gives you some information for your next patient conversation about constipation. Ask about the Rome criteria. Look at the available pharmacologic options, including over-the-counter medications and biointerventions that involve such food as peppermint oil, and consider what can potentially be done with diet manipulation. This is not "one shoe fits all" for what is a prevalent, global problem, but hopefully some of these points will resonate with you the next time you encounter a patient and need to select the best approaches to optimize management. Review this monograph in the American Journal of Gastroenterology[2]; I think you will find it helpful for your next patient with constipation or IBS. I'm Dr David Johnson. Thanks for listening.

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