Earlier this month, the November 2014 print edition of Gastroenterology published an article entitled, “American Gastroinenterological Association Institute Guideline on the Pharmacological Management of Irritable Bowel Syndrome.” The article was previously released in online format in September.
The four authors were David S. Weinberg, MD, MSc, Director of Gastroenterology at Fox Chase Cancer Center in Philadelphia, Walter Smalley, MD of the VA Tennessee Valley Healthcare System, Vanderbilt University, Joel J. Heidelbaugh, MD, of the University of Michigan at Ann Arbor, and Shahnaz Sultan, MD, MHSc of the Department of Veterans Affairs Medical Center North Florida/South Georgia Veterans Health System, University of Florida at Gainesville, and Minneapolis Veterans Affairs Health System, University of Minnesota at Minneapolis. They based their article on the work of the AGA Institute Clinical Guidelines Committee, which consisted of eleven additional gastroenterologists associated with nine different academic medical centers in the United States and Canada. The AGA technical review for these guidelines, addressing methods and possible biases in the various studies and providing additional details and commentary on the results, was authored by Lin Chang, MD of UCLA, Anthony Lembo, MD of Harvard Medical School and Beth Israel Deaconess in Boston, and Dr. Sultan.
The AGA’s new official guidelines focus on the use of nine common medications or classes of medication commonly used for the treatment of IBS with diarrhea (IBS-D) and IBS with constipation (IBS-C) in adults in the United States. There are no current medications available that are specifically aimed at treatment of IBS with alternating or mixed subtype (IBS-M). The report is not intended to address the treatment of children with IBS, nor non-medication options for adults such as diet, fiber, exercise, psychological therapies, complementary medicine, etc.
The guidelines are based on reviews of the scientific evidence thus far in multiple large randomly controlled trials for each medication or class of medications. The committee used standard procedures and best practices for its review, and assigned either a “strong” recommendation or “conditional” (weak) recommendation. By a “strong” recommendation, the committee deems the strength of evidence such that most people with IBS would likely desire to try this medication, that they would probably not need a significant amount of guidance to make a decision, that most medical professionals would find it appropriate to recommend to most people with the given IBS subtype, and that on a policy level, these medications could be considered a good quality standard of care in most situations. By a “conditional” recommendation, the committee concludes from the strength or weakness of evidence, that many people with IBS would likely desire to try a given medication but many others would not. For these medications, people with IBS and their physicians would have to take a more active role in “shared decision making” to determine if the specific medication is appropriate for the individual and consistent with his or her values (such as preferring to avoid side effects or extra out of pocket expenses, etc.) For these “conditional” recommendations, the guidelines state that further discussion among various stakeholders in the IBS community is necessary before adoption of major policy changes.
In all cases, the recommendations are “over no drug treatment,” meaning better than no treatment. There has been no apparent attempt in these recommendations to rank medication options in relation to each other. More details are available at the links to the article and the technical review, both of which are also downloadable in PDF format. Based on this work, the AGA now recommends as follows:
Linaclotide for IBS-C (Brand name Linzess in the United States and Canada, Constella in Europe): High quality evidence and strong recommendation by the committee. The article notes, however, that for those people concerned about costs or about the possible side effect of diarrhea (in a relatively small subset of study volunteers), they may prefer alternatives.
Lubiprostone for IBS-C (Brand name Amitiza): Moderate quality evidence and conditional recommendation by the committee. The article notes that there are few side effects, but those concerned about costs may prefer alternatives.
PEG (polyethylene glycol) laxatives for IBS-C: Low quality evidence and conditional recommendation by the committee. However, the article notes that there are few side effects and minimal costs associated with this class of treatment.
Comment by IBS Impact: The AGA article does not specify PEG laxatives that were reviewed, but as clarification for readers of this blog, one common brand name available without a prescription in the U.S. is Miralax.
Rifaximin for IBS-D (Brand name: Xifaxan): Moderate quality evidence and conditional recommendation by the committee. According to the article, side effects are relatively few, but the cost may be high.
Comment by IBS Impact: Please note that this medication is still undergoing the FDA approval process. In 2011, the FDA responded to a first application with a request for additional studies. At that time, the FDA expressed concerns, as some functional GI professionals continue to do, about the long-term effects of repeated use and possible eventual antibiotic resistance. Following additional promising results by Salix, the pharmaceutical company producing rifaximin, the FDA accepted a second application for review in September 2014. According to IFFGD, the FDA’s decision on rifaximin is expected by the end of February 2015. (Scroll down to “FDA Considers Rifaximin for Treatment of IBS-D.”)
Alosetron for IBS-D (Brand name Lotronex): Moderate quality evidence and conditional recommendation by the committee.
Comment by IBS Impact: Please note that this medication, intended only for extremely severe IBS-D that cannot be managed by other means, is currently available in the United States only under FDA-restricted status because of past history of severe side effects or death in some people. At this time, FDA approval is for adult women only, as there is insufficient evidence that it is effective in most men studied, and to our knowledge, this has not been researched in children.
Loperamide for IBS-D (Brand name Immodium, available in the U.S. without a prescription): Very low quality evidence and conditional recommendation from the committee. The article notes, however, that this medication is inexpensive, readily available over the counter, and may help reduce stool frequency, but is not effective for global IBS symptoms.
Tricylic anti-depressants: Low quality evidence and conditional recommendation from the committee. The article notes that this treatment is relatively low cost, but may cause disruption in the QT interval (a potentially serious cardiac problem) in some people.
Comment by IBS Impact: The AGA article does not specify which tricyclics were reviewed, but as clarification for readers of this blog, some examples of common tricyclics, by generic and U.S. brand names, are amitriptyline (Elavil), desipramine (Norpramin) imipramin (Tofranil), and nortriptyline (Pamelor).
Selective serotonin reuptake inhibitors (SSRIs), a different class of antidepressants: Low quality evidence and conditional recommendation from the committee. The article states that the risks of this treatment are low. However, from a total of 9 randomly controlled trials that the committee reviewed, they concluded there was no significant improvement in global symptoms or in abdominal pain specifically. Of all of the medications or classes of medication covered in these guidelines, this is the only category that the AGA now “recommends against.”
Comment by IBS Impact: This is an interesting result, as research has shown that IBS is partly the result of abnormalities in serotonin signaling and transport, and SSRIs, up until now, have generally been considered by GI professionals to be reasonable options for IBS. Again, the article does not state which SSRIs were reviewed, but as clarification for readers of this blog, some examples of common SSRIs by generic and U.S. brand names, are citalopram (Celexa), escitalopram (Lexapro), fluoxetine (Prozac), paroxetine (Paxil) and sertraline (Zoloft).
Antispasmodic (anticholinergic) medications: Low quality evidence and conditional recommendation from the committee. The article states that overall, 22 randomly controlled trials reviewed showed significant symptom improvement and few serious risks of treatment, but the overall quality of evidence is low due to differences in method, continuous versus as-needed use, publication bias and other differences. In addition, not all of the specific medications in the studies are available in the United States.
Comment by IBS Impact: Once again, the AGA article does not state which antispasmodics were reviewed, but as clarification for readers of this blog, some examples of common antispasmodics, by generic and U.S. brand names, are hyoscyamine (Levsin) and dicyclomine (Bentyl).
Gastroenterology professionals may be interested in an AGA online webinar on this subject with Dr. Chang and Dr. Sultan on December 16, 2014 from 12:00 noon to 1:00 pm Eastern time. Information and a link to the registration page can be found here. http://www.gastro.org/journals-publications/news/aga-s-new-ibs-guideline
Readers may recall that this blog reported on new evidence-based reviews from the American College of Gastroenterology as well on August 10, 2014. To clarify possible confusion, these are two separate U.S. national professional organizations. While many aspects of their reviews and guidelines overlap and many gastroenterology professionals are members of both, AGA and ACG’s respective reports are not the same.
IBS Impact appreciates the work of the AGA Clinical Guidelines C0mmittee, the named authors of the published article and technical review, and the AGA. Peer review is important to the scientific process and future advances. The availability of this document provides additional guidance to health care professionals and interested people with IBS in the most current standards of care for IBS in the United States. When so many people with IBS, families and professionals continue to receive outdated or inaccurate information about basic aspects of IBS, an evidence-based document is an important tool in education and management of IBS.