Targeted therapies for diarrhea-predominant irritable bowel syndrome

Abstract

Irritable bowel syndrome (IBS) causes gastrointestinal symptoms such as abdominal pain, bloating, and bowel pattern abnormalities, which compromise patients’ daily functioning. Common therapies address one or two IBS symptoms, while others offer wider symptom control, presumably by targeting pathophysiologic mechanisms of IBS. The aim of this targeted literature review was to capture clinical trial reports of agents receiving the highest recommendation (Grade 1) for treatment of IBS from the 2009 American College of Gastroenterology IBS Task Force, with an emphasis on diarrhea-predominant IBS. Literature searches in PubMed captured articles detailing randomized placebo-controlled trials in IBS/diarrhea-predominant IBS for agents receiving Grade I (strong) 2009 American College of Gastroenterology IBS Task Force recommendations: tricyclic antidepressants, nonabsorbable antibiotics, and the 5-HT3 receptor antagonist alosetron. Studies specific for constipation-predominant IBS were excluded. Tricyclic antidepressants appear to improve global IBS symptoms but have variable effects on abdominal pain and uncertain tolerability; effects on stool consistency, frequency, and urgency were not adequately assessed. Nonabsorbable antibiotics show positive effects on global symptoms, abdominal pain, bloating, and stool consistency but may be most efficacious in patients with altered intestinal microbiota. Alosetron improves global symptoms and abdominal pain and normalizes bowel irregularities, including stool frequency, consistency, and fecal urgency. Both the nonabsorbable antibiotic rifaximin and the 5-HT3 receptor antagonist alosetron improve quality of life. Targeted therapies provide more complete relief of IBS symptoms than conventional agents. Familiarization with the quantity and quality of evidence of effectiveness can facilitate more individualized treatment plans for patients with this heterogeneous disorder.

Reizdarmsyndrom – neue Entwicklungen

“…Die Bedenken in Form der Entwicklung einer Antibiotikaresistenz bei einem Krankheitsbild mit hoher Prävalenz in der Bevölkerung sowie chronischem und rekurrierendem Verlauf und damit der potenziellen Notwendigkeit einer wiederholten Therapie teilte auch die FDA, die eine Zulassung für das RDS ohne Obstipation nicht erteilte und weitere Daten zum wiederholten Einsatz des Präparates forderte [13]. Zu diesem Aspekt wurden bislang zwei Berichte publiziert [13,15], nach denen eine wiederholte RifaximinTherapie über 5 oder mehr Kurse effektiv war; die Wiederholungsintervalle lagen im Median zwischen 4 und 12 Monaten.…”

“…Zu diesem Aspekt wurden bislang zwei Berichte publiziert [13,15], nach denen eine wiederholte RifaximinTherapie über 5 oder mehr Kurse effektiv war; die Wiederholungsintervalle lagen im Median zwischen 4 und 12 Monaten. Prucaloprid Als Ausblick sei erwähnt, dass der dem Cisaprid sehr ähnliche 5-HT 4 -Rezeptor Agonist Prucaloprid (Resolor ® ), der ebenfalls als Prokinetikum im Gastrointestinaltrakt wirksam ist, in großen, kontrollierten randomisierten Studien eine gute Effektivität in der Therapie der chronischen Obstipation gezeigt hat.…”

Eluxadoline: a promising therapy that raises many questions

“…The pathogenesis of IBS is unclear, but the condition is generally believed to reflect the complex interactions between visceral hypersensitivity, environmental factors, stress, and the effects of altered serotonergic tone on gut motility (13). It is abundantly clear that there is not a single cause of IBS symptoms and the condition should be thought of as a syndrome of symptoms, rather than as a traditional disease state.…”

“…Additional etiologies that have been proposed for IBS underscore the wide range of possible causes and include (I) altered gut microbiota; (II) altered immune function; (III) inflammation; (IV) food intolerances; (V) post-infectious sequelae; (VI) impaired gas handling and (VII) altered motility due to volatile bacterial fermentation products (13)(14)(15)(16)(17). Historically, IBS therapies have tended to target single IBS symptoms, e.g., laxatives to treat constipation, anti-diarrheals to treat diarrhea, and anti-spasmodics to treat abdominal pain (13), all of which often fail to provide satisfactory relief of global IBS symptoms. Medications with multiple potential targets, designed to positively affect both gastrointestinal motility and abdominal pain, could be expected to have broader treatment effects than these symptom-directed therapies.…”

The comparison of treatments with and without azithromycin in irritable bowel syndrome with diarrhea-predominant in gastrointestinal Clinic of Al-Zahra Hospital, Isfahan, Iran

“…[9] The prevalence of IBS with diarrhea is approximately 3% among the general population in the UK[10] and ranged from 3% to 20% in North America. [11] IBS is more common in women than men. [21213] SEPAHAN systematic review also showed the greater prevalence in women than men.…”