Balancing Symptoms in Irritable Bowel Syndrome

Ondansetron relieved diarrhea in IBS patients

(RxWiki News) Irritable bowel syndrome affects more than one in 10 people, and a small subset have diarrhea associated with it. Living with the fear of unexpected, painful diarrhea can be debilitating.

There is a fine line between stopping the diarrhea in irritable bowel syndrome (IBS) and causing constipation. Recent advances in our understanding of how the gut and intestines are stimulated have produced ideas of how to control it.

Researchers tested whether a medication called ondansetron (brand name Zofran), which blocks some nerve transmissions in the gut, would work to control the diarrhea associated with some forms of IBS.

They found that ondansetron helped to relieve the frequency, urgency and loose stools of people with IBS and diarrhea.

"Ask your doctor how to treat diarrhea associated with IBS."

This team of researchers was led by Robin Spiller from Nottingham Digestive Diseases Biomedical Research Unit at Queens Medical Centre in Nottingham, UK.

Serotonin, also called 5-HT3, signals nerves in the gut to increase the movement of contents through the intestines. Ondansetron, which blocks the 5-HT3 receptor, has been effective in treating nausea and vomiting from chemotherapy. A side effect of treatment with this medication is constipation.

"Ondansetron (Zofran) has been used for several years as adjunctive therapy in combination with a wide variety of chemotherapy regimens. Being a 5-HT3 inhibitor, it works very well to decrease chemotherapy-induced nausea and vomiting (CINV)," said E. Lee Carter, RPh, Clinical Pharmacy Specialist at the Department of Veterans Affairs in Prestonsburg, Kentucky.

"Ondansetron has also become a favorite among anesthesia providers in reducing post-operative nausea and vomiting (PONV) caused by general anesthesia medications. Ondansetron generally has fewer side-effects and is better tolerated than some of the older medications previously used for CINV or PONV, such as Phenergan (promethazine), Tigan (trimethobenzamide), and Compazine (prochlorperazine). The (normally mild) side-effect of constipation stimulated research to explore whether Ondansetron might prove helpful in reducing IBS-associated diarrhea," Carter explained.

Spiller and team designed a study to test whether ondansetron would work to control the diarrhea associated with some types of IBS. Irritable bowel syndrome with diarrhea is referred to as IBS-D.

Study participants, ages 18-75, were enrolled from IBS clinics from January 2009 to May 2011. The researchers included 21 healthy people in the study for comparison.

Participants were chosen at random to receive ondansetron or placebo (fake medication) for five weeks. They were given one 4-mg tablet of ondansetron a day, and the dose was increased up to two tablets three times a day. The dose was determined by the degree of control the medication had over the diarrhea. Doses were adjusted over the first three weeks and then kept constant for weeks four and five.

Study medication and placebo were stopped for two weeks, and then the groups were switched. Those people who took ondansetron previously were given placebo, and those who took placebo were given ondansetron.

The treatments were given for another five weeks at the same doses and schedule as the first five weeks.

This study was designed so that neither the study investigators nor the study subjects knew who was receiving ondansetron and who was taking placebo.

If subjects in the study had uncontrolled diarrhea, they were given 2 mg of loperamide (brand name Imodium) twice daily.

Participants were given the Patient Health Questionnaire 15 to assess depression, and stress was assessed with scores on the Perceived Stress Scale Questionnaire. The IBS Quality of Life Questionnaire and the IBSS Severity Score Questionnaire were also given to the study subjects.

People in the study kept a daily diary of their stools. This allowed the researchers to get daily information on the consistency of stools, as well as other symptoms such as pain, urgency and bloating. Stools were classified form Type 1 (very hard) to Type 7 (water).

At week four, each study subject took 20 barium silicon markers by mouth, and the time it took for the markers to travel through their gut was measured by X-ray. This measurement was called transit time.

At the end of each five-week treatment period, the researchers asked the study subjects whether they got relief from their diarrhea in the last two weeks and which treatment they preferred — the first five week treatment they received or the second treatment.

Responses to treatment were determined using the FDA’s definition of response as a “patient who experiences a 50 percent or greater reduction in the number of days per week with at least one stool that has a consistency of Type 6 or 7 compared with baseline and a pain responder as a patient who experienced a fall of 30 percent in pain compared to baseline.”

At the end of the study, 47 patients had been treated with the ondansetron/placebo sequence and 51 had been given the placebo/ondansetron sequence of treatments. Twice as many people dropped out of the ondansetron/placebo treatment as did in the placebo/ondansetron treatment. The dropouts had more frequent stools per day than the people who stayed in the study.

Patients who took ondansetron experienced diarrhea relief, measured by firmer stools, within a week of treatment, and when treatment was discontinued, the diarrhea resumed. No effect on stool firmness was seen in patients on placebo treatment.

If patients started with severe diarrhea, however, the effect of ondansetron was lessened.

The data on pain, urgency and bloating showed that the average urgency scores reported by patients were significantly lower after taking ondansetron compared to placebo. The average number of stools a day also decreased significantly in the ondansetron group. Bloating was not significantly decreased.

A decrease in the number of days with loose stools was reported by 80 percent of the patients taking ondansetron treatment, compared to 41 percent of the participants on placebo.

Patients with IBS-D had faster gut transit times compared to healthy controls. The transit time of patients with IBS-D was an average of 16 hours, compared with 46 hours in controls. Transit time increased to 24 hours for IBS-D patients on ondansetron.

When patients were asked whether they got relief from their diarrhea in the last two weeks and which five-week treatment set they preferred, patients were four to five times more likely to prefer ondansetron and no placebo than placebo and no ondansetron.

Constipation was the most common side effect reported in the study. A total of 9 percent of patients taking ondansetron and 2 percent of people on placebo reported constipation.

The researchers concluded that ondansetron helped to control diarrhea in IBS. Patients reported less urgency and fewer loose stools when taking ondansetron. Because people with more severe IBS-D did not get as much relief from ondansetron, the authors suggested that best response to the treatment may be in patients with mild to moderate symptoms.

"Ondansetron seemed to perform well in this NIH-sponsored study looking at treatment options for IBS-D. In the same way it works to reduce CINV and PONV, it appears to slow gut transit time thereby decreasing the number of diarrhea episodes in patients who suffer with IBS," said Carter, who was not involved in this study.

"Ondansetron can also cause mild drowsiness, blurred vision, and dry mouth. For patients suffering from IBS, it may be worthwhile for patients to discuss with their primary care provider or pharmacist whether Ondansetron may be an viable alternative to help reduce their IBS-D symptoms," he said.

This research was published in the December issue of Gut.

Spiller disclosed receiving funding for his research from Lesaffre and Ironwood and was on the Advisory Boards for Almirall, Astellas, Danone and Sanofi. Free medication for this clinical trial was provided from Norgine.

This research was funded by a grant from the National Institute for Health Research.

Review Date: 
January 8, 2014