Itopride for Functional Dyspepsia
For patients with functional dyspepsia, treatment with itopride for 8 weeks provides a significantly greater reduction in symptoms than does placebo, according to results from a recent randomized trial.
Itopride is a dopamine D2 antagonist that inhibits acetylcholinesterase activity. In Japan, the drug is often prescribed for functional dyspepsia, even though it had not been evaluated in randomized, controlled trials.
In the current study, Dr. Gerald Holtmann of the University of Adelaide (Australia) and his associates randomized 554 patients with functional dyspepsia to receive itopride at 50 mg, 100 mg, or 200 mg three times daily or placebo (N. Engl. J. Med. 2006;354:832–40).
After 8 weeks, the overall response rate, defined by the patient's global assessment of efficacy, was significantly greater with itopride than with placebo (60% vs 41%). This was a dose-dependent effect, with response rates of 57% at 50 mg, 59% at 100 mg, and 64% at 200 mg.
The incidence of adverse events was similar for itopride (38%) and placebo (37%). Although prolactin levels increased significantly in the 100-mg and 200-mg itopride groups, no related clinical signs or symptoms were noted.
COX-2 Inhibitors in IBD Patients
Patients with ulcerative colitis in remission who had a history of nonspecific arthritis, arthralgia, or another condition treatable with NSAID therapy did not have a greater relapse rate with the use of celecoxib for up to 14 days than with placebo, Dr. William J. Sandborn and his colleagues reported.
In a double-blind, pilot trial, 221 patients were randomized to receive oral celecoxib 200 mg or placebo twice daily for 14 days. Ulcerative colitis (UC) exacerbation occurred in 3 of 110 evaluated patients on celecoxib and in 4 of 107 on placebo (Clin. Gastroenterol. Hepatol. 2006;4:203–11). The study was supported by a research grant from Pfizer Inc.
In a second study, Dr. Ken Takeuchi and his colleagues studied patients with quiescent Crohn's disease or UC. First, they randomized 109 patients to 4 weeks of treatment with either acetaminophen or a conventional NSAID (naproxen, diclofenac, or indomethacin). Of patients taking NSAIDs, 17%–28% had a relapse; whereas no patients taking acetaminophen relapsed (Clin. Gastroenterol. Hepatol. 2006;4:196–202).
None of the 100 patients in the second part of the study had an early relapse on acetaminophen, low-dose aspirin (selective COX-1 inhibitor), or nimesulide (selective COX-2 inhibitor not available in the United States). Those on naproxen (topical COX-1 and −2 inhibitor) or nabumetone (COX-1 and −2 inhibitor) had relapses associated with intestinal inflammation. The research was funded in part by grants from Merck Sharp & Dohme and Helsinn Pharmaceuticals, manufacturer of nimesulide.
The studies “indicate that nonselective inhibitors carry a significant risk for exacerbating IBD whereas celecoxib is safe for 2 weeks for patients in remission. Low-dose aspirin use remains in a gray zone of uncertain but probable safety,” said Dr. Joshua R. Korzenik and Dr. Daniel K. Podolsky of Harvard Medical School, Boston, in an editorial (Clin. Gastroenterol. Hepatol. 2006;4:157–9).
Treatment Options for Pancreatitis
Surgical drainage of the pancreatic duct was more effective for relieving pain than endoscopic drainage in a study of 39 patients with chronic pancreatitis.
“Surgery is safe and required fewer therapeutic interventions,” Dr. Djuna L. Cahen said at the 13th United European Gastroenterology Week. Surgery also led to faster pain relief, said Dr. Cahen, a gastroenterologist at the University of Amsterdam Academic Medical Center.
The study involved all patients referred to the Academic Medical Center from January 2000 to October 2004 with symptomatic, chronic pancreatitis and a dominant pancreatic duct obstruction caused by strictures or stones.
Of the 39 patients, 20 were randomized to surgical drainage by pancreaticojejunostomy and 19 underwent endoscopic drainage by stent insertion. Endoscopic treatment was preceded by extracorporeal shock wave lithotripsy in 16 patients who had stones causing the obstruction.
The study's primary end point was the average Izbicki pain score during a median follow-up of 24 months. The average pain score was 25 in the surgery group and 51 in the endoscopy group, a statistically significant difference.
Clinical success—defined as a reduction in the pain score of at least 50% from baseline to the end of follow-up—was achieved in 32% of endoscopy patients and 75% of surgery patients. The two groups did not differ in terms of complications, morbidity, mortality, or hospital length of stay.