Pediatric Irritable Bowel Syndrome Medication
- Author: Mohammad F El-Baba, MD; Chief Editor: Carmen Cuffari, MD more...
Medication Summary
Pharmacotherapy is recommended for patients with moderate-to-severe irritable bowel syndrome (IBS) symptoms that cause disruptions in activity. Treatment is symptomatic and is directed at the most predominant symptom (eg, dietary fiber supplementation and stool softeners for constipation, antidiarrheals for diarrhea, smooth muscle relaxants for pain). A better understanding of the pathophysiology of irritable bowel syndrome and the role of neurotransmitters and receptors involved in the GI sensory and motor functions have provided opportunities for the development of newer therapeutic agents. The role of serotonin in the pathophysiology of irritable bowel syndrome has drawn much attention, and agonists and antagonists at 5-hydroxytryptamine (5-HT) receptors have been approved for the treatment of subgroups of patients with irritable bowel syndrome.
Saps et al conducted a double-blind, placebo-controlled trial examining amitriptyline efficacy in treating children (n=83) with pain-predominant functional GI disorders (eg, irritable bowel syndrome, functional abdominal pain, functional dyspepsia).[15] Participants were randomized to receive 4 weeks of either placebo or amitriptyline (weight < 35 kg = 10 mg/d, weight >35 kg = 20 mg/d). The primary outcome, overall response to treatment (ie, child’s pain assessment and sense of improvement), indicated no difference between placebo and amitriptyline (57.5% improvement and 2.5% worsening with placebo compared with 63% improvement and 5% worsening with amitriptyline; P=0.63). Children with severe baseline pain in both groups had poorer response to treatment. Although placebo and amitriptyline both produced a therapeutic response of pain reduction, this study showed no significant difference between placebo and amitriptyline.
Antispasmodic and anticholinergic agents
Class Summary
These are the most frequently used medications (ie, hyoscyamine, dicyclomine) in the United States for the treatment of pain episodes in patients with irritable bowel syndrome. Results from adult studies on the efficacy of these medications have provided conflicting data. The meta-analysis of the use of smooth muscle relaxants (eg, cimetropium, otilonium bromide, pinaverium, mebeverine, trimebutine) by Poynard et al showed efficacy over placebo in irritable bowel syndrome.[16] These drugs have calcium channel–blocking properties or antimuscarinic activities. No pediatric data are available with which to evaluate their efficacy or adverse effects.
Hyoscyamine (Levsin, Levbid)
Blocks action of acetylcholine at parasympathetic sites in smooth muscle, secretory glands, and CNS, which in turn has antispasmodic effects.
Dicyclomine (Bentyl)
Treats GI motility disturbances. Blocks action of acetylcholine at parasympathetic sites in secretory glands, smooth muscle, and CNS.
Reports show that administration of dicyclomine syrup in infants has been followed by serious respiratory symptoms, seizures, syncope, pulse rate fluctuations, and coma. Death has been reported.
Antidiarrheal agents
Class Summary
These agents are used to treat diarrhea adjunctly with rehydration therapy to correct fluid and electrolyte depletion. They are usually helpful when diarrhea is the predominant symptom. Studies of the opiate agent loperamide show that it improves stool consistency, decreases stool frequency, and reduces abdominal pain. Cholestyramine acts by binding bile acids and can be helpful in some patients with irritable bowel syndrome. Alosetron and tegaserod are 5-HT4 receptor partial agonists that bind with high affinity at human 5-HT4 receptors. The activation of 5-HT4 receptors in the GI tract stimulates the peristaltic reflex and intestinal secretion and inhibits visceral sensitivity. In vivo studies showed that tegaserod enhanced basal motor activity and normalized impaired motility throughout the GI tract. In addition, studies demonstrated that tegaserod moderated visceral sensitivity during colorectal distension in animals.
Tegaserod was temporarily withdrawn from the US market in March 2007; however, as of July 27, 2007, restricted use of tegaserod is now permitted via a treatment IND protocol. The treatment IND allows tegaserod treatment of irritable bowel syndrome with constipation or chronic idiopathic constipation (CIC) in women younger than 55 years who meet specific guidelines. Its use is further restricted to those in critical need who have no known or preexisting heart disease.
Earlier this year, tegaserod marketing was suspended because of a meta-analysis of safety data pooled from 29 clinical trials that involved more than 18,000 patients. The results showed an excess number of serious cardiovascular adverse events, including angina, myocardial infarction, and stroke, in those taking tegaserod compared with placebo. In each study, patients were assigned at random to either tegaserod or placebo. Tegaserod was taken by 11,614 patients, and placebo was taken by 7,031 patients. The average age of patients in these studies was 43 years, and most patients (ie, 88%) were women. Serious and life-threatening cardiovascular adverse effects occurred in 13 patients (0.1%) treated with tegaserod; among these, 4 patients had a heart attack (1 died), 6 had unstable angina, and 3 had a stroke. Among the patients taking placebo, only 1 (0.01%) had symptoms suggesting the beginning of a stroke that went away without complication.
For more information, see the FDA MedWatch Product Safety Alert.
Loperamide (Imodium)
Synthetic opioid; does not have central nervous action in therapeutic doses. Acts by slowing intestinal motility and enhancing water and electrolyte absorption. Reduces diarrhea and pain in patients with diarrhea-predominant IBS.
Cholestyramine (Prevalite, Questran)
Binds endogenous bile acids and can improve diarrhea in patients with unexplained diarrhea or idiopathic bile acid malabsorption.
Alosetron (Lotronex)
Potent and selective antagonist of serotonin 5-HT3 receptor type. 5-HT3 receptors are extensively located on enteric neurons of GI tract, and stimulation causes hypersensitivity and hyperactivity of intestine. Alosetron blocks these receptors and, thus, is effective in controlling IBS symptoms.
Only approved for treatment in women with severe, chronic, diarrhea-predominant IBS that has failed to respond to conventional IBS therapy. Less than 5% of IBS is considered severe, and only a fraction of severe cases are diarrhea-predominant IBS. Limiting use to this severely affected population is intended to maximize the benefit-to-risk ratio. Previously removed from US market but reintroduced with new restrictions approved by FDA on June 7, 2002. Restricted because serious and unpredictable GI adverse events (some of which resulted in death) were reported in association with its use following original approval in February 2000.
Tegaserod hydrogen maleate (Zelnorm)
NOTE: As of April 2008, no longer available in US.
Previously available in US by restricted treatment IND for irritable bowel syndrome with constipation (IBS-C) or chronic idiopathic constipation (CIC) in women younger than 55 years who meet specific guidelines. Indicated for the short-term treatment of women with irritable bowel syndrome in which constipation is the predominant symptom. Serotonin type 4 receptor partial agonist with no affinity for 5-HT3 receptors. May trigger peristaltic reflex via 5-HT4 activation, which enhances basal motor activity and normalizes impaired GI motility. Research studies have shown inhibitory activity of drug on visceral activity in GI tract.
Antidepressant drugs
Class Summary
Numerous studies have shown that TCAs (ie, imipramine, amitriptyline) can be useful in the treatment of irritable bowel syndrome in some patients. In addition to their antidepressant effects, TCAs have neuromodulatory and analgesic properties, which can be achieved at lower doses than those required for treatment of depression. Because of their inhibitory effect on gut motor function, TCAs may benefit patients with irritable bowel syndrome with predominant diarrhea or pain. TCAs particularly benefit patients with irritable bowel syndrome who have well-defined depression or panic attacks.
Amitriptyline (Elavil)
Inhibits reuptake of serotonin and/or norepinephrine at presynaptic neuronal membrane, which increases concentration in CNS.
Imipramine (Tofranil)
Inhibits reuptake of norepinephrine or serotonin (5-HT) at presynaptic neuron.
Laxatives and stool softeners
Class Summary
These agents can be useful in patients with constipation-predominant irritable bowel syndrome. Osmotic laxatives (eg, magnesium hydroxide, lactulose, sorbitol) or stool lubricants (eg, mineral oil) are usually required for long-term therapy for children with moderate-to-severe constipation. Long-term studies have shown that these medications are safe and equally effective. Stimulant laxatives may be necessary intermittently and for short periods, but avoid prolonged use.
Mineral oil (Milkinol)
An emollient laxative that does not appear to have any pharmacologic action on the GI tract. Acts by lubrication. When taken for 2-3 d, penetrates and softens stool and may interfere with absorption of water. Generally is well tolerated and without major adverse effects. Onset of action is approximately 6-8 h. Indigestible; limited absorption.
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