Pharmacological Therapies and Their Clinical Targets in Irritable Bowel Syndrome With Diarrhea

Abstract

Irritable bowel syndrome (IBS) is one of the most common disorders of the gut-brain axis, which affects approximately 4% of the global population. The Rome IV criteria define IBS as chronic or recurrent abdominal pain associated with altered bowel habits. Patients can be categorized in four subtypes: IBS with predominant constipation (IBS-C), predominant diarrhea (IBS-D), mixed bowel habits (IBS-M), and unclassified (IBS-U). IBS is associated with a lower quality of life, reduced work productivity, and high healthcare costs. When comparing subtypes, patients with IBS-D report lower disease related quality of life. Due to the scope of this review, we have solely focused on patients with IBS-D. Choosing the right pharmacological treatment in these patients remains challenging due to the heterogeneous patient population, patients' expectation of the treatment outcome, unavailability of efficacious drugs, and the multifactorial and incompletely understood underlying pathophysiology. Currently, pharmacological treatment options target individual symptoms, such as abdominal pain, altered bowel habits, and bloating. In this review, we aimed to summarize the current and recent pharmacological treatment options in IBS-D, targeting the predominant gastrointestinal symptoms. Additionally, we proposed a pharmacological treatment algorithm which healthcare professionals could use when treating individual patients with IBS-D.

Keywords: abdominal pain; bloating; clinical management algorithms; diarrhea—therapy; irritable bowel syndrome (IBS); irritable bowel syndrome with diarrhea; loose stools; pharmacology.

FIGURE 1

Peppermint oil targeting abdominal pain in IBS. Enteric-coated peppermint oil capsules are released in the small intestine causing a modulation of visceral sensation, smooth muscle relaxation, a modulation of the immune system, and a modulation of the microbiome. The agent is anti-viral and anti-fungal. All proposed mechanisms of action can lead to a decrease in abdominal pain perception. Created with BioRender.com.

FIGURE 2

Mechanisms of action of pharmacological treatments in IBS-D. 5-HT₃ receptor antagonists, targeting 5-HT₃ receptors located on enteric neurons, myenteric plexus, submucosal plexus, and primary afferent neurons, reducing sensory signals, secrotory and motor reflex in the gut. Eluxadoline (opioid receptors agonist), targeting δ-,µ-, and κ-opioid receptors located on enteric neurons, myenteric plexus, submucosal plexus, and primary afferent neurons delaying transit by reducing secretory and sensory signals. Rifaximin, targeting the luminal gut microbiome due to its non-absorbable and non-systemic properties. Created with BioRender.com.

FIGURE 3

Probiotics and their symptom target in patients with IBS. Different probiotics, assessed in former and more recent RCTs, can target individual IBS symptoms. RCTs either demonstrated a significant effect on global IBS symptoms, abdominal pain, bowel habits, flatulence, bloating or abdominal distention or a combination thereof. * indicated the number of bacterial strains included in the mixture. Created with BioRender.com.

FIGURE 4

Predominant symptom-based algorithm for pharmacological treatments in IBS-D 5-HT3-RA, 5-hydroxytryptamine-3 receptor antagonists; IBS, irritable bowel syndrome; IBS-D, IBS with predominant diarrhea; TCA, tricyclic antidepressants; SSRI, serotonin re-uptake inhibitors. Created with BioRender.com.