Spherical Carbon Adsorbent AST-120 Improves Nonconstipating IBS Symptoms
The oral, nonabsorbed, carbon-based adsorbent AST-120 has been safely used in more than 360,000 Japanese patients and has been evaluated in patients with chronic kidney disease, Crohn’s disease, and type 2 diabetes. The agent appears to adsorb substances implicated in the patho-genesis of IBS, including bacterial toxins and bile acids. In a randomized, double-blind, placebo-controlled trial, Tack and colleagues evaluated the safety and efficacy of AST-120 in patients with diarrhea-predominant or alternating IBS. After a 2-week run-in period, a total of 115 patients were randomly assigned to AST-120 2 g (56 patients) or placebo (59 patients) administered 3 times per day for 8 weeks. All patients subsequently received placebo for a 2-week washout period, followed by an 8-week phase of open-label AST-120. Patients were considered responders if they had a reduction of at least 50% in days with pain over the previous 2 weeks of treatment compared to the run-in period. Severity of pain and bloating were assessed using 100-mm visual analog scales. Response rates were significantly higher with AST-120 versus placebo at Treatment Week 4 (27% vs 10%; P=.029) and increased to 32% versus 25%, respectively, at Week 8, regardless of gender or IBS subtype. Over the course of the 8-week randomized phase, responses were achieved in 21% of patients receiving AST-120 versus 11% of patients receiving placebo. Compared to placebo, AST-120 was also associated with greater mean reductions in bloating severity at Week 2 (13 mm vs 2 mm; P=.007) and Week 4 (14 mm vs -1 mm; P=.002). Patients receiving AST-120 were also more likely to attain at least a 1-point improvement in stool consistency and a greater improvement in regard to the effects of IBS symptoms on daily activities. These benefits abated during the washout period but resumed upon restarting AST-120 therapy. The agent appeared tolerable; more than 85% of patients in both groups completed the 8-week randomized phase, and adverse event rates were lower with AST-120 versus placebo.
Psychological Distress Associated With Development of Functional Gastrointestinal Disorders in Healthy Individuals
The exact causes of functional gastrointestinal disorders (FGIDs) have not been elucidated, though several etiologic factors have been proposed. Koloski and colleagues conducted a 12-year longitudinal, prospective, population-based cohort study evaluating the role of psychological factors in the development of FGIDs. The study, initiated in 1997, included 1,175 individuals from Penrith, Australia, 591 of whom did not meet Rome II diagnostic criteria for FGIDs. After 12 years, 35% of these participants had developed FGIDs, including functional abdominal bloating (11%), functional heartburn (11%), IBS (6%), and functional dyspepsia (4%). The investigators reported a significant correlation between anxiety levels in 1997 and diagnosis of an FGID in 2009. For every 5-point change in score on the Delusions-Symptom-States Inventory scale, the risk of FGID diagnosis was increased by 59% (odds ratio [OR], 1.59; 95% CI, 1.11—2.26; P=.01). This relationship remained after controlling for age, gender, and medication use for gastrointestinal symptoms. FGIDs that correlated with high anxiety at baseline included functional abdominal bloating (OR, 1.62; 95% CI, 1.04—2.52; P=.03) and functional dyspepsia (OR, 2.86; 95% CI, 1.62—5.08; P<.001). Only functional dyspepsia remained an independent predictor (OR, 2.64; 95% CI, 1.44—4.84; P=.002). The presence of depression at baseline was also a significant independent predictor of functional dyspepsia at follow-up (OR, 2.51; 95% CI, 1.28—4.93; P=.007).