Citations

Chronic abdominal pain is a common gastrointestinal (GI) symptom that characterizes many functional GI disorders/disorders of gut-brain interaction, including irritable bowel syndrome, functional dyspepsia, and centrally mediated abdominal pain syndrome. The symptoms of abdominal pain in these highly prevalent disorders are often treated with antispasmodic agents. Antispasmodic treatment includes a broad range of therapeutic classes with different mechanisms of action, including anticholinergic/antimuscarinic agents (inhibition of GI smooth muscle contraction), calcium channel inhibitors (inhibition of calcium transport into GI smooth muscle), and direct smooth muscle relaxants (inhibition of sodium and calcium transport). The aim of this review article was to examine the efficacy and safety of antispasmodics available in North America (e.g., alverine, dicyclomine, hyoscine, hyoscyamine, mebeverine, otilonium, pinaverium, and trimebutine) for the treatment of chronic abdominal pain in patients with common disorders of gut-brain interaction. For the agents examined, comparisons of studies are limited by inconsistencies in treatment dosing and duration, patient profiles, and diagnostic criteria employed. Furthermore, variability in study end points limits comparisons. Risk of selection, performance, detection, attrition, and reporting bias also differed among studies, and in many cases, risks were considered “unclear.” The antispasmodics evaluated in this review, which differ in geographic availability, were found to vary dramatically in efficacy and safety. Given these caveats, each agent should be considered on an individual basis, rather than prescribed based on information across the broad class of agents.

Background: Eluxadoline, a United States Food and Drug Administration (FDA)-approved treatment for irritable bowel syndrome with diarrhea (IBS-D), underwent a change to its US prescribing information on 21 April 2017, contraindicating it in patients without a gallbladder due to increased risk of pancreatitis. This study aimed to elucidate the potential role of eluxadoline’s label change on the number of reported spontaneous adverse events (AEs) of pancreatitis. Methods: A pharmacovigilance database (Oracle Argus) was searched for eluxadoline use and spontaneously reported pancreatitis cases from 1 January 2016 to 30 June 2018. Pancreatitis cases were reported as a proportion of the total number of reported AE cases in the safety database. The FDA’s adverse event reporting system (AERS) was also interrogated for cases of pancreatitis concomitantly reported with eluxadoline use. Results: In patients who received eluxadoline, 273 reported cases of pancreatitis were recorded (total AEs n = 2191; 12.5%). When known, 28.2% of patients reporting pancreatitis had intact gallbladders (49/174). Eluxadoline was withdrawn in 97.5% of cases, with 87.1% of patients improving or recovered at time of reporting. Importantly, the reporting proportion of pancreatitis cases decreased from 14.4% to 8.9% post label change. Findings were supported by the AERS results, which demonstrated a decrease in reporting proportion from 21.2% to 12.8%. Conclusions: While cautious interpretation is warranted, post-marketing data indicate that the contraindication of eluxadoline in patients without a gallbladder led to reduced reported cases of pancreatitis, with no additional reports of moderately severe or severe cases. Eluxadoline is a safe and well-tolerated treatment option for IBS-D when used according to the label.

Irritable bowel syndrome (IBS) is a highly prevalent, chronic disorder that significantly reduces patients' quality of life. Advances in diagnostic testing and in therapeutic options for patients with IBS led to the development of this first-ever American College of Gastroenterology clinical guideline for the management of IBS using Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology. Twenty-five clinically important questions were assessed after a comprehensive literature search; 9 questions focused on diagnostic testing; 16 questions focused on therapeutic options. Consensus was obtained using a modified Delphi approach, and based on GRADE methodology, we endorse the following: We suggest that a positive diagnostic strategy as compared to a diagnostic strategy of exclusion be used to improve time to initiating appropriate therapy. We suggest that serologic testing be performed to rule out celiac disease in patients with IBS and diarrhea symptoms. We suggest that fecal calprotectin be checked in patients with suspected IBS and diarrhea symptoms to rule out inflammatory bowel disease. We recommend a limited trial of a low fermentable oligosaccharides, disacchardies, monosaccharides, polyols (FODMAP) diet in patients with IBS to improve global symptoms. We recommend the use of chloride channel activators and guanylate cyclase activators to treat global IBS with constipation symptoms. We recommend the use of rifaximin to treat global IBS with diarrhea symptoms. We suggest that gut-directed psychotherapy be used to treat global IBS symptoms. Additional statements and information regarding diagnostic strategies, specific drugs, doses, and duration of therapy can be found in the guideline.

Eating disorders involve irregularities in eating behavior that may cause gastrointestinal (GI) symptoms. Consequently, many patients with eating disorders seek gastroenterological healthcare at some point in their illness, with many seeking this care even before they seek treatment for and/or diagnosed with their eating disorder. As such, the gastroenterology provider is in a unique position to identify, manage, and facilitate treatment for an eating disorder early in the course of the illness. Although assessing eating disorders is already a difficult task, the identification of eating disorders in patients with GI disease represents an even greater challenge. In particular, common GI symptoms, such as nausea, vomiting, and bloating, may disguise an eating disorder because these symptoms are often viewed as a sufficient impetus for dietary restriction and subsequent weight loss. In addition, the focus on identifying an organic etiology for the GI symptoms can distract providers from considering an eating disorder. During this prolonged diagnostic evaluation, the eating disorder can progress in severity and become more difficult to treat. Unfortunately, a misconception that hinders eating disorder detection is the notion that the rate or method of weight loss is associated with an eating disorder. Regardless of whether weight loss is slow or rapid, purposeful or accidental, eating disorder behaviors and thought patterns may be present. Unidentified eating disorders are not only dangerous in their own right but also can interfere with effective management of GI disease and its symptoms. As such, it is imperative for the GI provider to remain well versed in the identification of these diseases.