ONDASETRON FOR IRRITABLE BOWEL SYNDROME

NEW YORK (Reuters Health) Jan 08 - Ondansetron relieved some of the most annoying symptoms of irritable bowel syndrome with diarrhea (IBS-D), in a randomized trial from the UK.

At doses commonly used in clinical practice, ondansetron improved stool consistency, stool frequency, urgency, and bloating but not abdominal pain, the authors wrote online December 12 in Gut.

Ondansetron is an inexpensive generic drug that's available worldwide and has a long history of safe use, the authors say.

"Diarrhea can be due to many causes so an accurate diagnosis is the most important thing in management," said principal investigator Dr. Robin Spiller of the University of Nottingham Medical School, in email to Reuters Health.

"Once other causes of diarrhea such as inflammatory bowel disease have been excluded, then the patient's diet should be examined to ensure there is no dietary cause including lactose intolerance or excessive intake of poorly absorbed foods," he said.

"If none of these things help, then ondansetron is a safe simple treatment. The benefit is usually seen within a few days, so it can be discontinued if there is no benefit within two weeks," he added.

Dr. Spiller and his colleagues enrolled 120 adults who met the Rome III criteria for IBS-D in a randomized, double-blind, placebo-controlled crossover study in two centers. The majority were female, with a mean age of about 40.

For the first five weeks, patients took 4 mg of ondansetron or placebo, with dose titration allowed, up to two tablets three times a day, followed by a two-week washout period, followed by the second 5 weeks of crossover treatment. The primary endpoint was average stool consistency in the last two weeks of treatment.

Ultimately, 47 (77%) patients took ondansetron followed by placebo and 51 (88%) patients took placebo followed by ondansetron.

The patients kept daily records of their stool consistency using the Bristol Stool Form score, and their gut transit was measured during the last week of each treatment.

Almost twice as many patients dropped out from the ondansetron-first group than from the placebo-first group (p=0.110), most of them during the placebo period.

The researchers found that ondansetron significantly improved stool consistency, with the mean difference in stool form of -0.9 between ondansetron and placebo (p<0 .001="" benefited="" diarrhea.="" diarrhea="" from="" however="" less="" more="" note="" ondansetron="" p="" patients="" people="" severe="" than="" they="" with="">

Compared with placebo, patients on ondansetron experienced an average of 1.1 fewer days per week with urgency (p<0 .001="" 0-3="" 0.13="" 0.32="" 11="" a="" an="" and="" bloating="" but="" defecation="" drop="" frequency="" in="" levels.="" near="" of="" on="" p="" pain="" previous="" reduction="" scale="" stayed="" urgency="">

The IBS symptom severity score fell by 83 points with ondansetron vs 37 points with placebo (p=0.001), with a drop of 50 points considered clinically significant.

Whole gut transit time also increased by a mean of 10 hours (p<0 .001="" p="">

Overall, 65% of patients reported adequate relief with ondansetron but not placebo, compared with 14% who reported relief with placebo but not ondansetron (relative risk 4.7, p<0 .001="" p="">

The only frequent side effect was constipation, in 9% on ondansetron and 2% on placebo.

"This is not yet the standard the care. IBS is a complex disease, and this study shows that ondansetron may be a treatment option. Longer-term data are needed because of the chronic nature of this disease and the side effects seen with similar drugs such as alosetron," said Dr. Ira Daniel Breite, who was not involved in the study, in an email. Dr. Breite is on the gastroenterology faculty at New York University School of Medicine.

"If more standard treatments are not working, physicians should consider using ondansetron to treat IBS-D. Until more data are available, caution should be used in giving this drug long term," he said.

Dr. William D. Chey, a gastroenterologist at the University of Michigan Health System in Ann Arbor, said in an email, "It has long been known that alosetron, another 5-hydroxytryptamine 3 (5-HT3) antagonist, provides significant benefits to women and men with severe IBS-D.

"Unfortunately, dose-dependent constipation and idiosyncratic ischemic colitis have limited its availability. In the US, alosetron is only available for women with severe IBS-D who have failed to improve with standard therapies," he added. Dr. Chey was not involved in the study.

"The strong preference of patients with IBS-D for the drug over placebo despite the fact that it did not alter pain much suggests that urgency and loose stools are the most important aspect of the condition. This is not surprising given the socially disabling nature of fecal urgency which disrupts travelling, eating out and public engagements," Dr. Spiller said.

"Patients with very severe diarrhea tended to do less well, so they probably need a different treatment or perhaps ondansetron plus an opioid," he added.

SOURCE: http://bit.ly/1eHJlqH

Gut 2013.