Evaluation of Treatments for IBS

Summarized by Robert W. Griffith, MD
January 31, 2003 (Reviewed: January 21, 2005)

Introduction

A Task Force established by the American College of Gastroenterology, which was charged with reviewing the available evidence on treatment modalities for irritable bowel syndrome (IBS), reported their findings in November 2002.¹ This is a summary of their principal conclusions.

Methodology

A comprehensive literature search was done to identify relevant IBS therapy studies. Only treatments available in the USA were included. The Task Force employed a commonly-used system to grade the evidence of effectiveness for the treatments they evaluated; they were assisted in these activities by a medical education and research company.²

The graded levels of evidence, together with the Task Force recommendations, are summarized in this table:

Evidence & Recommendations
Level I evidence	Randomized controlled trials, adequate size, etc
Level II evidence	Randomized controlled trials, inadequate size, etc
Level III evidence	Non-randomized controlled trials
Level IV evidence	Non-randomized trials using historical controls
Level V evidence	Case studies
Grade A recommendations	Supported by Level I evidence
Grade B recommendations	Supported by Level II evidence
Grade C recommendations	Supported by Level III-IV evidence

Note: evidence for Levels I & II have studies with p values <0.05.

The Task Force members believe that Grade A recommendations, supported by Level 1 evidence, represent accurate information. Grade B recommendations have intermediate-quality evidence (Level II), and may therefore have important limitations. The strength of Grade C recommendations is limited by the quality of the source of the information.

Diagnostic approach to IBS

The definition of IBS is symptom-based, and an accurate history is important - abdominal pain, bloating, diarrhea, fecal urgency, or constipation. As a broad definition, the following can be used: "abdominal discomfort associated with altered bowel habits". For patients over 50, colon cancer screening tools should be applied first. In other (younger) age groups, only 'alarm symptoms', such as bloody stools, 10-pound weight loss, recurring fever, anemia, and chronic severe diarrhea justify a full gastroenterology work-up before IBS is diagnosed as the cause.

Treatment of IBS is indicated when the patient and the physician believe the symptoms diminish the patient's quality-of-life. The Task Force recommends classifying IBS patients based on their symptomatology:

• IBS alternating between diarrhea and constipation;
• IBS associated with abdominal discomfort, bloating, and constipation;
• IBS associated with abdominal discomfort, fecal urgency, and diarrhea.

Therapeutic modalities

The Task Force evaluated the therapeutic effectiveness of the following treatment modalities: antispasmodic agents, bulking agents, loperamide, antidepressants, tegaresod, aldosetron, and behavioral therapy. This is what they recommend:

Antispasmodic agents (hyoscyamine and dicyclomine in the USA): "There are insufficient data to make a recommendation about the effectiveness of the antispasmodic agents available in the United States (Grade B recommendation)". Only one of three studies meeting the required standards showed a statistically significant benefit on global IBS symptoms. At high doses, antispasmodics may produce atropine-like side-effects.

Bulking agents (e.g .wheat bran, corn fiber, calcium polycarbophil, psyllium): "Bulking agents commonly available in the United States are not more effective than placebo at relieving global IBS symptoms (Grade B recommendation)." None of the 13 trials identified had adequate methodology, and evidence of benefit on symptomatology was slight, if any. The conclusion: "fiber is appropriate for treatment of constipation but may not be recommended for treatment of IBS".

Loperamide (antidiarrheal agent): ". . . is not more effective than placebo at relieving IBS symptoms (Grade B recommendation)." Three acceptable trials examine the use of loperamide in IBS patients with diarrhea; in general, stool frequency and stool consistency were improved but bloating and abdominal pain were unaffected.

Antidepressants (tricyclic antidepressants [TCAs] and selective serotonin reuptake inhibitors [SSRIs]): ". . . TCAs are not more effective than placebo at relieving global IBS symptoms . . ." but they do improve abdominal pain. This is a Grade B recommendation, based on what are termed "studies of low quality" (six) or a "high drop-out rate" (one). The effectiveness of SSRIs in IBS has not yet been fully documented.

Tegaserod (5HT4 receptor antagonist): ". . . is more effective than placebo at relieving global IBS symptoms in female IBS patients with constipation (Grade A recommendation)." Tegaserod is the only available 5HT4 antagonist, and its effectiveness in IBS associated with constipation has been demonstrated in 4 high-quality 12-week clinical studies. Not surprisingly, diarrhea is the commonest adverse effect. Although over 80% of the people in the trials were women, and the FDA's approval of the drug is limited to women, the men in the trials reported significant benefits.

Alosetron (5HT3 receptor antagonist): ". . . is more effective than placebo at relieving global IBS symptoms in female IBS patients with diarrhea (Grade A recommendation)." As with tegaserod, the effectiveness of alosetron has been demonstrated in 4 high-quality 12-week clinical studies. After approval in the USA, marketing of the drug was halted in 2000 because of concerns about the occurrence of ischemic colitis in some patients. The FDA permitted restricted marketing to be resumed in June 2002 for treating "women with severe, diarrhea-predominant IBS who have failed to respond to conventional IBS therapy". Constipation is the most common adverse event, and patients should discontinue temporarily if it is severe.

Behavioral therapy:". . . is more effective than placebo at relieving individual IBS symptoms (Grade B recommendation)." Behavioral approaches include relaxation therapy to reduce stress, biofeedback regulation of bowel habits, hypnotherapy directed at intestinal muscle contraction, cognitive therapy, and psychotherapy. The Task Force evaluated 16 trials, which they considered of intermediate quality. Over 80% of the patients included in most trials had other psychological disorders along with their IBS. In 11 of the 16 studies IBS symptoms were significantly improved, compared with control groups; in 5, there were no significant improvements.

Comment

All treatments of disease are 'works in progress' - in other words, some traditional therapies are accepted as being useful without necessarily good evidence, some have proven effectiveness, and some have not yet been studied fully. So the present analysis represents a 'snapshot'. The Task Force lamented the paucity of good quality studies, and it must be emphasized that the only high-quality Level I evidence, for or against effectiveness, came from studies sponsored by the manufacturers of the two drugs in question - tegaserod and alosetron. It is unlikely that treatments that don't carry similar prospects for financial return will ever be examined in studies rigorous enough to receive a Level I accolade.

The end result of this assessment is that only the two Grade A recommendations - tegaserod and alosetron - and behavioral therapy (Grade B) are endorsed for use in managing IBS. This represents a much narrower viewpoint than that put forward in a recent Lancet review, recently summarized on this site (see first link below).

Sources

• Evidence-based position statement on the management of irritable bowel syndrome in North America.  American College of Gastroenterology Functional Gastrointestinal Disorders Task Force, Am J Gastroenterol, 2002, vol. 97, pp. 1--5



• Systematic Review on the management of irritable bowel syndrome in North America. LJ. Brandt, D. Bjorkman, MB. Fennerty,  et al., Am J Gastroenterol, 2002, vol. 97, pp. 7--26

Footnotes
1. The work of the Task Force was supported by an unrestricted grant from Novartis Pharmaceuticals.
2. EBMed, LLC, Anaheim Hills, California. The three principals of EBMed, who are gastroenterologists, are among the ten co-authors of the final task force report.

Related Links
Differential Diagnosis and Management of IBS - Update

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