Irritable Bowel Syndrome Medication

The selection of pharmacologic treatment remains symptom directed. Agents used for management of symptoms in irritable bowel syndrome (IBS) include anticholinergics, antidiarrheals, tricyclic antidepressants, prokinetics, bulk-forming laxatives, serotonin receptor antagonists, and chloride channel activators.

A Cochrane systematic review found that several antispasmodics, including peppermint oil, pinaverium, trimebutine, and cimetropium/dicyclomine, significantly outperformed placebo at improving IBS symptom and global assessment scores.^[15]

The 2009 ACG position statement on management of IBS noted that the antidiarrheal agent loperamide effectively reduced stool frequency and improved stool consistency, but it did not relieve pain, bloating, or other global IBS symptoms.^[14]

Investigational use

A total of 1260 patients with IBS without constipation were enrolled in the TARGET 1 and TARGET 2 phase III trials at 179 investigative sites in the United States and Canada. Results showed that treatment with rifaximin (550 mg PO tid for 14 d) provided better symptom relief (eg, bloating, abdominal pain, loose/watery stools) compared with placebo, although the placebo effect was tremendous. Similarly, a 2012 meta-analysis of 5 studies, incorporating 1,803 patients, determined that rifaximin is more effective than placebo for global symptom relief and bloating. Adverse event rates were similar to placebo.^[19] Rifaximin is not yet approved by the US Food and Drug Administration for IBS.^[20]

Class Summary

Anticholinergic agents are antispasmodics that inhibit intestinal smooth-muscle depolarization at the muscarinic receptor. These agents help relieve symptoms of intestinal spasms in irritable bowel syndrome.

Dicyclomine hydrochloride (Bentyl)

Dicyclomine blocks the action of acetylcholine at parasympathetic sites in secretory glands, smooth muscle, and CNS. This drug decreases fecal urgency and pain. It is useful with diarrhea-predominant symptoms. Adverse effects are dose dependent.

Hyoscyamine sulfate (Levsin)

Like dicyclomine, hyoscyamine is useful in patients with diarrhea-predominant symptoms and blocks action of acetylcholine at parasympathetic sites in smooth muscle, secretory glands, and the CNS, which, in turn, has antispasmodic effects. The drug decreases fecal urgency and pain.

Class Summary

These agents are nonabsorbable synthetic opioids. They prolong GI transit time and decrease secretion via peripheral µ-opioid receptors. They reduce visceral nociception via afferent pathway inhibition.

Diphenoxylate hydrochloride 2.5 mg with atropine sulfate 0.025 mg (Lomotil)

This drug combination consists of 2.5 mg of diphenoxylate, which is a constipating meperidine congener, and 0.025 mg of atropine to discourage abuse. The preparation inhibits excessive GI propulsion and motility, but it may exacerbate constipation.

Loperamide (Imodium)

Loperamide, which is available over the counter, acts on intestinal muscles to inhibit peristalsis and to slow intestinal motility. It prolongs movement of electrolytes and fluid through bowel and increases viscosity and loss of fluids and electrolytes. Loperamide improves stool frequency and consistency, reduces abdominal pain and fecal urgency, and may exacerbate constipation.

Class Summary

Tricyclic antidepressants have both antidepressive and analgesic properties. Agents such as imipramine and amitriptyline are efficacious in treating symptoms of irritable bowel syndrome. The use of tricyclic antidepressants in irritable bowel syndrome is off label.

Imipramine (Tofranil)

Imipramine increases pain threshold in the gut, thereby providing a visceral analgesic effect. It prolongs oral-cecal transit time; reduces abdominal pain, mucorrhea, and stool frequency; and increases global well-being variably in studies. It is effective in irritable bowel syndrome in doses subtherapeutic for antidepressive actions, suggesting an independent mechanism of action in this disorder.

Amitriptyline (Elavil)

Like imipramine, amitriptyline provides a visceral analgesic effect at doses subtherapeutic for antidepressive actions. It also prolongs oral-cecal transit time, reduces abdominal pain, mucorrhea, and stool frequency, and increases global well-being variably in studies.

Class Summary

5-HT3 receptor antagonists inhibit activation of nonselective cation channels, which modulate the enteric nervous system.

Alosetron (Lotronex)

Alosetron controls irritable bowel syndrome symptoms through its potent and selective antagonism of serotonin 5-HT3 receptor type. These receptors are extensively located on enteric neurons of the GI tract, and stimulation causes hypersensitivity and hyperactivity of the intestine. This agent is approved only for women with severe chronic diarrhea-predominant IBS who have not responded to conventional therapy.

Fewer than 5% of irritable bowel syndrome cases are considered severe, and only a fraction of severe cases are diarrhea-predominant IBS. Limiting its use to this severely affected population is intended to maximize the benefit-to-risk ratio. The drug was previously removed from the US market but was reintroduced with new restrictions approved by the FDA on June 7, 2002. Restrictions are because of serious and unpredictable GI adverse events (including some that resulted in death) reported in association with its use following its original approval in February 2000.

Under the new management plan, serious adverse events have been few.^[21]

Class Summary

Antibiotics may play a role in the treatment of irritable bowel syndrome by preventing the overgrowth of intestinal bacteria.

Rifaximin (Xifaxan)

Rifaximin has been studied in patients with irritable bowel syndrome and is believed to improve the symptoms of bloating, diarrhea, abdominal pain, and constipation. Rifaximin is a nonabsorbed (< 0.4%), broad-spectrum antibiotic specific for enteric pathogens (ie, gram-positive, gram-negative, aerobic and anaerobic) of the GI tract. It is indicated for Escherichia coli (enterotoxigenic and enteroaggregative strains) associated with travelers' diarrhea.

Class Summary

These agents enhance chloride-rich intestinal fluid secretions without altering sodium and potassium concentrations in the serum.

Lubiprostone (Amitiza)

This agent activates chloride channels on the apical part of the small bowel epithelium. As a result, chloride ions are secreted and sodium and water passively diffuse into the lumen to maintain isotonicity. This medication is FDA approved for use in idiopathic constipation and in irritable bowel syndrome with constipation.

Class Summary

These products are made of natural and semi-synthetic hydrophilic polysaccharides and cellulose derivatives that dissolve or swell in the intestinal fluid, forming emollient gels that facilitate passage of intestinal contents and stimulate peristalsis. As fiber supplements, these products may improve symptoms of constipation and diarrhea, but their use in irritable bowel syndrome is controversial.

Methylcellulose (Citrucel)

This agent promotes bowel evacuation by forming a viscous liquid and promoting peristalsis.

Psyllium (Metamucil, Fiberall, Reguloid, Konsyl)

Like methylcellulose, psyllium promotes bowel evacuation by forming a viscous liquid and promoting peristalsis.