Editor's Note: In March 2007 the FDA asked Novartis -- the maker of Zelnorm -- to pull the drug from the market because of evidence that it raises the risk of heart attacks and stroke. But in July 2007 the FDA ruled that Zelnorm may be used by some patients in critical need of the drug who do not have heart problems.
May 23, 2001 (Atlanta) -- It seems it's been all bad news lately for people with irritable bowel syndrome. Lotronex, the drug with so much hope, was voluntarily removed from the market this past November after some patients experienced life-threatening side effects, and before that Propulsid -- which was linked to serious heart problems -- became unavailable this past July. But now, things are looking up.
This week, researchers at the Digestive Disease Week conference here presented new findings that could mean relief for the one in five Americans suffering from the pain, bloating, diarrhea, and constipation of IBS.
According to Martin Lefkowitz, MD, "there is no proven effective therapy for the group of IBS patients with abdominal pain, bloating, and constipation." But within a week of being on a new drug called Zelnorm, "these patients had significantly less discomfort and improved quality of life," he says.
After a four-week observational period, Lefkowitz' team randomly assigned more than 1,500 female volunteers with IBS to a 12-week course of twice-daily Zelnorm or placebo. The women all had moderate to severe abdominal pain and three or more bowel movements per week, usually with straining.
Zelnorm "stimulates motility or movement of the digestive tract, stimulates intestinal secretions, and inhibits visceral sensitivity or the perception of pain," says Lefkowitz. He is director of clinical research at Zelnorm manufacturer Novartis Pharmaceuticals Corporation, in East Hanover, N.J.
The new drug works by mimicking the effects of the naturally occurring chemical called serotonin, says Lefkowitz. Lotronex, in contrast, did essentially the opposite. It inhibited the action of serotonin and was recommended for IBS patients whose primary complaint is diarrhea.
Considerably more patients in the Zelnorm group than in the placebo group reported complete or considerable relief from IBS symptoms, and a significant increase in their overall sense of well-being. "Zelnorm twice a day results in rapid improvement of multiple IBS symptoms," and the effect lasted as long as they continued the medication, he tells WebMD.
So far, extensive research has revealed no worrisome side effects with the drug. The most common problems have been headache and nausea. "There was a two-fold increase in diarrhea in about 6% of those taking Zelnorm, but it resolved by itself, did not cause dehydration, and most patients were able to continue in the study," says Lefkowitz. Even so, he cautions that anyone whose IBS symptoms include diarrhea should not take the drug.
Zelnorm is currently under FDA review with approval expected by summer, says Lefkowitz.
Help is also on the way for those suffering mainly with diarrhea. A new drug, cilansetron, is now in the final stages of clinical trial, and approval is right around the corner, says IBS researcher Michael Camilleri, MD, professor of medicine and physiology at the Mayo Clinic in Rochester, Minn. This drug falls into the same serotonin-inhibiting class as the now-defunct drug Lotronex, he says.
And in other drug development, researchers are trying to modulate the pain-messaging pathway, and a compound known only as substance P in particular. "P stands for pain," says Camilleri, "and the theory is that in IBS, something has gone wrong with the transmission of pain signals from the gut to the brain." These new compounds will try to short-circuit those faulty signals, he explains.
Even with these promising new drugs on the horizon, there will likely be "some IBS patients who do not respond to any available treatment," says researcher Francis Creed, MD, of Manchester University in England. "About 50% of them have depression or anxiety in addition to their IBS symptoms."
Creed's team looked specifically at this hardest-to-treat group, randomly assigning them to receive eight weeks of standard medical treatment from a gastroenterologist, eight weeks of Prozac, or eight weeks of one-on-one psychotherapy session. They followed the patients for a full year after treatment.
Overall, psychotherapy was more effective than Prozac, and Prozac was more effective than standard medical treatment at improving overall quality of life. Interestingly, although the one-on-one counseling was most expensive in the short term, it was least expensive in the long term, due to fewer doctor visits, drug prescriptions, and lost work time, says Creed.
"Psychotherapy really worked in about two-thirds of these patients," he says. This was true regardless of the patient's specific IBS symptoms, and especially for those patients with a history of childhood abuse.
Most important, says Creed, "patients in the psychotherapy group reported significant improvement in their quality of life, even if their IBS symptoms did not change. They still had pain," he says, "but they were better able to cope with it." He advises all IBS patients who are experiencing depression or anxiety in addition to their physical symptoms to seek counseling.